Assessing and treating mammals having metabolic disorders

Abstract

This document provides methods and materials for assessing and / or treating mammals (e.g., humans) having a metabolic disorder (e.g., a congenital disorder of glycosylation (CDG)). For example, a circulating glycopeptide signature present in blood of a mammal (e.g., a human) having a CDG can be used to identify the mammal as having a phosphomannomutase 2 (PMM2)-CDG. This document also provides methods and materials for treating a mammal having a CDG (e.g., PMM2-CDG).

Description

[0001] Attorney Docket No.07039-2225WO1 / 2023-182 ASSESSING AND TREATING MAMMALS HAVING METABOLIC DISORDERS CROSS-REFERENCETORELATEDAPPLICATIONSThis application claims the benefit of U.S. Patent Application Serial No.63 / 529,913, filed on July 31, 2023. The disclosure of the prior application is considered part of, and is incorporated by reference in, the disclosure of this application. STATEMENT REGARDING FEDERAL FUNDING This invention was made with government support under NS115198 and CA271410 awarded by the National Institutes of Health. The government has certain rights in the invention. SEQUENCE LISTING This application contains a Sequence Listing that has been submitted electronically as an XML file named “07039-2225WO1_SL.xml.” The XML file, created on July 30, 2024, is 258,097 bytes in size. The material in the XML file is hereby incorporated by reference in its entirety. TECHNICAL FIELD This document relates to methods and materials for assessing and / or treating mammals (e.g., humans) having a metabolic disorder (e.g., a congenital disorder of glycosylation (CDG)). For example, a circulating glycopeptide signature present in blood of a mammal (e.g., a human) having a CDG can be used to identify the mammal as having a phosphomannomutase 2 (PMM2)-CDG. This document also provides methods and materials for treating a mammal having a CDG (e.g., PMM2-CDG). BACKGROUNDINFORMATIONCDG are rare genetic diseases affecting essential processes of polypeptide and lipid modification by addition of sugar chains—a process called glycosylation. Pathogenic variants in the PMM2 gene, located on chromosome 16p13, lead to PMM2-CDG, with an estimated prevalence of 1:20,000-80,000. See, for example, Altassan et al., J. Inherit. Metab. Dis., 42(1):5-28 (2019). The diagnosis of most PMM2-CDG patients under the age of 2 years Attorney Docket No.07039-2225WO1 / 2023-182 is missed, mainly because of the early nonspecific presentation of the disease with hypotonia and feeding difficulties. The PMM2-CDG disease burden is significant. In addition to endocrine and coagulation abnormalities, PMM2-CDG patients can experience global developmental delays, ataxia, seizures, and progressive neuropathy. There is high lethality in the early years of life due to severe infections, liver insufficiency, and / or cardiomyopathy, with over 20% of patients not surviving beyond the age of 6 years. Other than PMM2-CDG, nearly 200 different CDG are known including MPI-CDG (caused by pathogenic variants in the MPI gene), SRD5A3-CDG (caused by pathogenic variants in the SRD5A3 gene) and MAN1B1-CDG (caused by pathogenic variants in the MAN1B1 gene). See for example, Matthijs et al., Nat. Genet.16(1):88-92 (1997); Ferreira et al., J. Inherit. Metab. Dis., 41(3):541-53 (2018); and Matthijs et al., Hum. Mutat., 16(5):386-94 (2000). Current methods for diagnosing CDG (e.g., PMM2-CDG) include genetic diagnostics such as whole exome sequencing and mass spectrometry detection of carbohydrate-deficient transferrin (CDT). See, for example, Biffi et al., Clin. Biochem., 40(18):1431-1434 (2007). Unfortunately, the results of these methods are frequently unclear due to, for example, the presence of variants of uncertain significance in the PMM2 gene and overlap of PMM2 polypeptide activity between patients and carriers. SUMMARYThere is a need to be able to identify mammals that have particular forms of CDG and select an appropriate treatment. This document is based, at least in part, on the discovery that particular circulating glycopeptides can be used to identify a mammal (e.g., a human) as having PMM2-CDG. This document provides methods and materials for assessing and / or treating mammals (e.g., humans) having a CDG. For example, the methods and materials provided herein can be used to determine if a mammal has PMM2-CDG based, at least in part, on the presence of a circulating glycopeptide signature in a sample (e.g., a blood sample) obtained from the mammal. A glycopeptide can be described by the polypeptide (or a peptide derived therefrom) that is glycosylated as well as by both the amino acid residue to which a glycan is attached (e.g., covalently attached) and the particular glycan (e.g., the particular carbohydrate composition) that is attached to the polypeptide to form a glycopeptide. For example, a Attorney Docket No.07039-2225WO1 / 2023-182 glycopeptide having a glycan containing 5 hexose moieties (Hex5) and two N- acetylhexosamine moieties (HexNAc2) attached to asparagine at amino acid residue 226 can be described as a (Asn226: Hex5HexNAc2) polypeptide. Glycans are abbreviated herein as set forth in the Symbol Nomenclature for Glycans (SNFG; see, e.g., Symbol Nomenclature for Graphical Representation of Glycans, Glycobiology, 25:1323-1324 (2015); and Updates to the Symbol Nomenclature for Glycans guidelines, Glycobiology, 29:620-624 (2019)). Abbreviations for exemplary glycans that can be present on one or more glycopeptides that can be used to determine if a mammal has PMM2-CDG as described herein can be as shown in Example 3. In some cases, a circulating glycopeptide signature that can be used to determine if a mammal has PMM2-CDG can include an altered level (e.g., an elevated level or a decreased level) of one or more glycopeptides. For example, a circulating glycopeptide signature that includes one or more (e.g., one, two, three, four, five, six, seven, or eight) of an elevated level of a complement component 4 (C4) (Asn226: Hex5HexNAc2) polypeptide, an elevated level of an orosomucoid 1 (ORM1) (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an orosomucoid 2 (ORM2) (Asn103: Hex1HexNAc2) polypeptide, an elevated level of a coagulation factor XII (F12 or FXII) (Asn249: Hex1HexNAc2) polypeptide, an elevated level of a haptoglobin (HP) (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, an elevated level of a haptoglobin (HP) (Asn211: Hex5HexNAc4NeuAc2) polypeptide, an elevated level of a haptoglobin (HP) (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and an elevated level of a complement component 7 (C7) (Asn202: Hex3HexNAc2) polypeptide in a sample (e.g., a blood sample) obtained from a mammal having a CDG can be used to identify that mammal as having PMM2-CDG. In another example, a circulating glycopeptide signature that lacks each of an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide in a sample (e.g., a blood sample) obtained from a mammal Attorney Docket No.07039-2225WO1 / 2023-182 having a CDG can be used to identify that mammal as having a CDG that is not PMM2- CDG. This document also provides methods and materials for treating a mammal having a CDG. For example, a mammal (e.g., a human) having a CDG can be administered one or more treatments that are selected based, at least in part, on the presence of a circulating glycopeptide signature in blood of a mammal. As demonstrated herein, glycopeptides can be secreted by cells of organs affected by PMM2-CDG such that the circulating glycopeptide signature of a blood sample obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having PMM2-CDG or as having a CDG that is not PMM2-CDG. For example, the presence of one or more of: an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide in a sample (e.g., a blood sample) from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having PMM2-CDG. The ability to distinguish between PMM2-CDG and a CDG that is not PMM2-CDG as described herein (e.g., by determining the circulating glycopeptide signature of a blood sample obtained from a mammal (e.g., a human) having a CDG) provides a unique and unrealized opportunity to tailor appropriate treatments for the mammals (e.g., humans) having either PMM2-CDG or a CDG that is not PMM2-CDG. In general, one aspect of this document features methods for assessing a mammal having a congenital disorder of glycosylation (CDG). The methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Attorney Docket No.07039-2225WO1 / 2023-182 Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) identifying the mammal as having a phosphomannomutase 2 (PMM2)-CDG. In some cases, the mammal is a human. In some cases, the method includes determining the presence of (1). In some cases, the method includes determining the presence of (2). In some cases, the method includes determining the presence of (3). In some cases, the method includes determining the presence of (4). In some cases, the method includes determining the presence of (5). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (6). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (7). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (8). In some cases, the method includes determining the presence of each of (1)-(8). In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, the each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for assessing a mammal having a congenital disorder of glycosylation (CDG). The methods can include, or consist essentially of (a) determining that a blood sample from the mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) identifying the mammal as having a CDG that is not a phosphomannomutase 2 (PMM2)-CDG. In some cases, the mammal is a human. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is Attorney Docket No.07039-2225WO1 / 2023-182 not glycosylated at Asn207. In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for selecting a treatment for a mammal having a CDG. The methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) selecting the mammal to receive a PMM2-CDG treatment. In some cases, the PMM2-CDG treatment includes administering a PMM2 polypeptide (or nucleic acid encoding the PMM2 polypeptide) to the mammal. In some cases, the PMM2 polypeptide includes an amino acid set forth in SEQ ID NO:1 or a variant thereof. In some cases, the method also includes administering the PMM2-CDG treatment to the mammal. In some cases, the mammal is a human. In some cases, the method includes determining the presence of (1). In some cases, the method includes determining the presence of (2). In some cases, the method includes determining the presence of (3). In some cases, the method includes determining the presence of (4). In some cases, the method includes determining the presence of (5). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (6). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (7). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (8). In some cases, the method includes determining the presence of each of (1)-(8). In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N- acetylglucosamine (GlcNAc). In another aspect, this document features methods for selecting a treatment for a mammal having a CDG. The methods can include, or consist essentially of (a) determining Attorney Docket No.07039-2225WO1 / 2023-182 that a blood sample from the mammal lacks the presence of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) selecting the mammal to receive a CDG treatment that is not a PMM2-CDG treatment. In some cases, the CDG treatment includes administering one or more monosaccharides or derivatives thereof to the mammal. In some cases, the one or more monosaccharides or derivatives thereof includes one or more of galactose, mannose, and mannose-1-phosphate. In some cases, the method also includes administering the CDG treatment to the mammal. In some cases, the mammal is a human. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for treating a mammal having a CDG. The methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) administering a PMM2-CDG treatment to the mammal. In some cases, the PMM2-CDG treatment includes administering a PMM2 polypeptide (or nucleic acid encoding the PMM2 polypeptide) to the mammal. In some cases, the PMM2 polypeptide includes an amino acid set forth in SEQ ID NO:1 or a variant thereof. In some Attorney Docket No.07039-2225WO1 / 2023-182 cases, the mammal is a human. In some cases, the method includes determining the presence of (1). In some cases, the method includes determining the presence of (2). In some cases, the method includes determining the presence of (3). In some cases, the method includes determining the presence of (4). In some cases, the method includes determining the presence of (5). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (6). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (7). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, the method includes determining the presence of (8). In some cases, the method includes determining the presence of each of (1)-(8). In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for treating a CDG. The methods can include, or consist essentially of administering a PMM2-CDG treatment to a mammal that was identified as having a blood sample comprising the presence of at least one of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. In some cases, the PMM2-CDG treatment includes administering a PMM2 polypeptide (or nucleic acid encoding the PMM2 polypeptide) to the mammal. In some cases, the PMM2 polypeptide includes an amino acid set forth in SEQ ID NO:1 or a variant thereof. In some cases, the mammal is a human. In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (1). In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (2). In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (3). In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (4). In Attorney Docket No.07039-2225WO1 / 2023-182 some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (5). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (6). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (7). In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of (8). In some cases, the mammal is a mammal that was identified as having a blood sample comprising the presence of each of (1)-(8). In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for treating a mammal having a CDG. The methods can include, or consist essentially of (a) determining that a blood sample from the mammal lacks the presence of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) administering a CDG treatment that is not a PMM2- CDG treatment to the mammal. In some cases, the CDG treatment includes administering one or more monosaccharides or derivatives thereof to the mammal. In some cases, the one or more monosaccharides or derivatives thereof includes one or more of galactose, mannose, and mannose-1-phosphate. In some cases, the mammal is a human. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). Attorney Docket No.07039-2225WO1 / 2023-182 In another aspect, this document features methods for treating CDG. The methods can include, or consist essentially of administering a CDG treatment that is not a PMM2-CDG treatment to a mammal that was identified as having a blood sample that lacks the presence of each of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. In some cases, the CDG treatment includes administering one or more monosaccharides or derivatives thereof to the mammal. In some cases, the one or more monosaccharides or derivatives thereof includes one or more of galactose, mannose, and mannose-1-phosphate. In some cases, the mammal is a human. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, the HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, each Hex in (1)-(8) is a mannose (Man). In some cases, each HexNAc in (1)-(8) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for assessing a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide; (2) an elevated level of an alpha-2-HS-glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide; and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide; and (b) identifying the mammal as having a mannose phosphate isomerase (MPI)-CDG. The mammal can be a human. In some cases, each Hex in (1)-(4) is a mannose (Man). In some cases, each HexNAc in (1)-(4) is an N- acetylglucosamine (GlcNAc). In another aspect, this document features methods for selecting a treatment for a mammal having a CDG, where the methods can include, or consist essentially of (a) Attorney Docket No.07039-2225WO1 / 2023-182 determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide; (2) an elevated level of an alpha-2-HS-glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide; and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide; and (b) selecting the mammal to receive a MPI-CDG treatment. The MPI-CDG treatment can include administering a MPI polypeptide (or nucleic acid encoding the MPI polypeptide) to the mammal. The MPI polypeptide can include the amino acid set forth in SEQ ID NO:173 or a variant thereof. The method can include administering the MPI-CDG treatment to the mammal. The mammal can be a human. In another aspect, this document features methods for treating a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide; (2) an elevated level of an alpha-2-HS-glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide; and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide; and (b) administering a MPI-CDG treatment to the mammal. The MPI-CDG treatment can include administering a MPI polypeptide (or nucleic acid encoding the MPI polypeptide) to the mammal. The MPI polypeptide can include the amino acid set forth in SEQ ID NO:173 or a variant thereof. The mammal can be a human. In another aspect, this document features methods for assessing a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide or an apoB100 (Asn3465:Hex3HexNAc3) polypeptide; (2) an elevated level of an alpha-2-macroglobulin ??2M) (Asn869:Hex3HexNAc2) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide; and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide; and (b) identifying the mammal as having a steroid 5-alpha-reductase 3 (SRD5A3)-CDG. The mammal can be a human. In some cases, each Hex in (1)-(4) is a mannose (Man). In some case, each HexNAc in (1)-(4) is an N- Attorney Docket No.07039-2225WO1 / 2023-182 acetylglucosamine (GlcNAc). In some cases, the HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide is not glycosylated at Asn207. In another aspect, this document features methods for selecting a treatment for a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide or an apoB100 (Asn3465:Hex3HexNAc3) polypeptide; (2) an elevated level of an alpha-2-macroglobulin (?2M) (Asn869:Hex3HexNAc2) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide; and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide; and (b) selecting the mammal to receive a SRD5A3-CDG treatment. The SRD5A3-CDG treatment can include administering a SRD5A3polypeptide (or nucleic acid encoding the SRD5A3 polypeptide) to the mammal. The SRD5A3 polypeptide can include the amino acid set forth in SEQ ID NO:175 or a variant thereof. The method can include administering the SRD5A3-CDG treatment to the mammal. The mammal can be a human. In another aspect, this document features methods for treating a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide or an apoB100 (Asn3465:Hex3HexNAc3) polypeptide; (2) an elevated level of an alpha-2-macroglobulin ??2M) (Asn869:Hex3HexNAc2) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide; and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide; and (b) administering a SRD5A3-CDG treatment to the mammal. The SRD5A3-CDG treatment can include administering a SRD5A3 polypeptide (or nucleic acid encoding the SRD5A3 polypeptide) to the mammal. The SRD5A3 polypeptide can include the amino acid set forth in SEQ ID NO:175 or a variant thereof. The mammal can be a human. In another aspect, this document features methods for assessing a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) Attorney Docket No.07039-2225WO1 / 2023-182 polypeptide or an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide; (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide; and (4) an elevated level of a C4B- binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide; and (b) identifying the mammal as having a mannosyl-oligosaccharide 1,2-alpha-mannosidase (MAN1B1)-CDG. The mammal can be a human. In some cases, each Hex in (1)-(4) is a mannose (Man). In some cases, each HexNAc in (1)-(4) is an N-acetylglucosamine (GlcNAc). In another aspect, this document features methods for selecting a treatment a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) polypeptide or an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide; (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide; and (4) an elevated level of a C4B-binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide; and (b) selecting the mammal to receive a MAN1B1-CDG treatment. The MAN1B1-CDG treatment can include administering a MAN1B1 polypeptide (or nucleic acid encoding the MAN1B1 polypeptide) to the mammal. The MAN1B1 polypeptide can include the amino acid set forth in SEQ ID NO:177 or a variant thereof. The method can include administering the MAN1B1-CDG treatment to the mammal. The mammal can be a human. In another aspect, this document features methods for treating a mammal having a CDG, where the methods can include, or consist essentially of (a) determining that a blood sample from the mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) polypeptide or an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide; (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide; and (4) an elevated level of a C4B- binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide; and (b) administering a MAN1B1-CDG treatment to the mammal. The MAN1B1-CDG treatment can include administering a MAN1B1polypeptide (or nucleic acid encoding the MAN1B1polypeptide) to Attorney Docket No.07039-2225WO1 / 2023-182 the mammal. The MAN1B1polypeptide can include the amino acid set forth in SEQ ID NO:177 or a variant thereof. The mammal can be a human. Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention pertains. Although methods and materials similar or equivalent to those described herein can be used to practice the invention, suitable methods and materials are described below. All publications, patent applications, patents, and other references mentioned herein are incorporated by reference in their entirety. In case of conflict, the present specification, including definitions, will control. In addition, the materials, methods, and examples are illustrative only and not intended to be limiting. The details of one or more embodiments of the invention are set forth in the accompanying drawings and the description below. Other features, objects, and advantages of the invention will be apparent from the description and drawings, and from the claims. DESCRIPTION OF THE DRAWINGS Figures 1A – 1E. Figure 1A contains a schematic showing a role for a phosphomannomutase (PMM2) polypeptide in polypeptide N-glycosylation. Figure 1B is a schematic of an exemplary experimental procedure for performing tandem mass tags (TMT) glycoproteomics with serum samples. Figure 1C is a plot of a partial least squares- discriminant analysis (PCA) of glycoproteomics data. Figure 1D is a volcano plot showing global glycosylation changes with selected glycopeptides that are altered in abundance marked as crosses (X’s). Figure 1E is a chord diagram of glycopeptides that showed changes in site-specific glycosylation. Figures 2A – 2C show site-specific glycoproteomic changes. Figure 2A is series of box plots representing levels of altered glycopeptides. *=q<0.05, **=q<0.01, ***=q<0.001; putative structures were drawn following SNFG guidelines and represent glycan composition inferred from mass spectrometry data (62); ORM1=Alpha-1-acid glycoprotein 1, ORM2=Alpha-1-acid glycoprotein 2, F12=coagulation factor XII, ATRN=attractin, LGALS3BP=galectin-3-binding protein, TF=transferrin, SERPINA1=alpha-1-antitrypsin, HPX=hemopexin, F2=prothrombin, APOH=beta-2-glycoprotein 1, SERPINA4=kallistatin, CD207=C-type lectin domain family 4 member K, GALNT5= Polypeptide N- Attorney Docket No.07039-2225WO1 / 2023-182 acetylgalactosaminyltransferase 5, SERPING1=plasma protease C1 inhibitor. Figure 2B is a heatmap showing differentially increased (q<0.05) glycopeptides in PMM2-CDG samples compared to matched controls. Figure 2C is a heatmap showing differentially decreased (q<0.05) glycopeptides in PMM2-CDG compared to matched controls; glycopeptides are represented by protein followed by the amino acid site of glycosylation and glycan composition. Hex=hexose, HexNAc=N-acetylglucosamine, NeuAc=N-acetylneuraminic acid, Fuc=fucose. Figures 3A-3E show results from a microheterogeneity analysis of glycosylation for selected proteins. Figures 3A-3B are a series of box plots showing relative abundance of glycopeptides bearing different glycans at the same site in (Figure 3A) Complement C4 Asn226and (Figure 3B) Ceruloplasmin Asn138. Figure 3C is a series of box plots showing relative abundance of representative haptoglobin-derived glycopeptides containing Asn207and Asn211but with glycan occupancy only at Asn207and with Asn211unglycosylated. Figure 3D is a series of box plots showing relative abundance of representative haptoglobin-derived glycopeptides containing Asn207and Asn211but with glycan only at Asn211and with Asn207unglycosylated. Figure 3E is a series of box plots showing relative abundance of representative haptoglobin-derived glycopeptides containing Asn207and Asn211with glycosylation at both Asn207and Asn211; *=q<0.05, **=q<0.01, ***=q<0.001; putative structures are shown using SNFG and represent total composition of glycan(s) inferred from mass spectrometry data. Figures 4A – 4D show results from a label-free glycoproteomics analysis. Figure 4A is a schematic of an exemplary experimental procedure for a mixed anion-exchange cartridges (MAX)-based enrichment and analysis. Figure 4B is a heatmap showing glycopeptides identified by label-free analysis using discovery methods. Figure 4C is an annotated MS / MS spectrum for a Man5GlcNAc2 glycopeptide from complement C4 (SEQ ID NO: 7). Figure 4D is a box plot of normalized peak intensity values for the Man5GlcNAc2glycopeptide from complement C4 at site Asn226; sample 3 was from an individual affected with PMM2-CDG at baseline, and sample 15 was from the same individual at 6 months of therapy with epalrestat; sample 24 was from an affected individual after liver transplantation; ND=not detected. Attorney Docket No.07039-2225WO1 / 2023-182 Figures 5A – 5D show results from experiments that validated the detection of the Man5GlcNAc2 glycopeptide from complement C4 as having alternative glycosylation patterns using a targeted analysis by parallel reaction monitoring (PRM). Figure 5A is an exemplary schematic for MAX-based enrichment and targeted analysis of glycopeptides. Figure 5B is a representative chromatogram of extracted ions in a sample from an individual with PMM2-CDG showing abundance of a Man5GlcNAc2glycopeptide from complement C4 at Asn226. Figure 5C is a representative chromatogram of extracted ions in a control sample of the same retention time as Figure 5B. Figure 5D is a dot plot showing abundance of the Man5GlcNAc2glycopeptide from complement C4 at Asn226in PMM2-CDG and control samples used for development of PRM assay; ND=not detected. Figures 6A-6H show detection of Man5GlcNAc2 glycopeptide from complement C4 at Asn226by blinded analysis correctly identifies individuals with PMM2-CDG. Representative Skyline plots showing glycopeptide fragment peaks from selected samples in the blinded set. Targeted analysis was performed by PRM by operators blinded to the identity of the samples. Representative Skyline plots of samples identified to be from individuals with PMM2-CDG are shown in Figures 6A-6D. Representative Skyline plots of samples identified to be from individuals without PMM2-CDG (controls) are shown in Figures 6E-6H. Figure 7A-7B show increased levels of unoccupied glycosylation sites on the indicated polypeptides. Figure 7A shows a series of box plots of the relative abundance of transferrin (TF)-derived polypeptides with non-glycosylated sites Asn432and Asn630. Figure 7B shows a series of box plots of the relative abundance of indicated polypeptides with unoccupied glycosylation sites as indicated; C4 = Complement C4, CP = Ceruloplasmin, SERPINA1 = Alpha-1-antitrypsin, ORM1 / ORM2 = Alpha-1-acid glycoproteins 1 / 2 (ORM1 / ORM2). Figures 8A – 8C show results of a serum glycoproteomics analysis. Figure 8A is a bar plot showing the distribution of glycopeptides by class (e.g., high mannose, paucimannose, and complex / hybrid). Figure 8B is a bar plot showing the distribution of glycopeptides by composition (e.g., sialylated, fucosylated, sialylated and fucosylated, and neither sialylated nor fucosylated). Figure 8C is a bar plot showing the number of paucimannose and high mannose glycopeptides containing different numbers of mannose units. Attorney Docket No.07039-2225WO1 / 2023-182 Figures 9A-9B show results of a serum glycoproteomics analysis in MPI-CDG. Figure 9A is a volcano a volcano plot showing global glycosylation changes with selected glycopeptides that were altered in abundance (indicated with a “x” on the plot). Figure 9B is a series of box plots representing levels of altered glycopeptides in MPI-CDG. Figures 10A-10B show results of a serum glycoproteomics analysis in SRD5A3- CDG. Figure 10A is a volcano a volcano plot showing global glycosylation changes with selected glycopeptides that were altered in abundance (indicated with a “x” on the plot) Figure 10B is a series of box plots representing levels of altered glycopeptides in SRD5A3- CDG. Figures 11A-11B show results of a serum glycoproteomics analysis in MAN1B1- CDG. Figure 11A is a volcano a volcano plot showing global glycosylation changes with selected glycopeptides that were altered in abundance (indicated with a “x” on the plot). Figure 11B is a series of box plots representing levels of altered glycopeptides in MAN1B1- CDG. Figures 12A-12C show glycopeptide alterations in the abundant secreted protein albumin. Figure 12A is a series of box plots showing altered levels of albumin-derived glycopeptides in PMM2-CDG. Figure 12B is a series of box plots showing altered levels of albumin-derived glycopeptides in SRD5A3-CDG. Figure 12C is a box plot showing altered levels of an albumin-derived glycopeptide in MAN1B1-CDG. DETAILED DESCRIPTION This document provides materials and method for assessing and / or treating mammals (e.g., humans) having a CDG (e.g., PMM2-CDG). In some cases, the circulating glycopeptide signature present in blood of a mammal (e.g., a human) having a CDG can be used to identify that mammal (e.g., human) as having PMM2-CDG or as having a CDG that is not PMM2-CDG. For example, a circulating glycopeptide signature that can be used to identify a mammal (e.g., a human) having a CDG as having PMM2-CDG can include at least one of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, Attorney Docket No.07039-2225WO1 / 2023-182 (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. In another example, a circulating glycopeptide signature that can be used to identify a mammal (e.g., a human) having a CDG as having a CDG that is not PMM2-CDG can lack each of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. Any appropriate mammal having a CDG can be assessed and / or treated as described herein. Examples of mammals that can have a CDG and that can be assessed and / or treated as described herein include, without limitation, humans, non-human primates (e.g., monkeys), dogs, cats, horses, cows, pigs, sheep, rabbits, mice, and rats. For example, a human having a CDG can be assessed and / or treated as described herein. In some cases, a human having a CDG that can be assessed and / or treated as described herein can be a newborn. For example, a human newborn that can be assessed and / or treated as described herein can be from about 1 day to about 1 month of age. In some cases, a human having a CDG that can be assessed and / or treated as described herein can be an infant. For example, a human infant that can be assessed and / or treated as described herein can be from about 1 month to about 1 year of age. In some cases, a human having a CDG that can be assessed and / or treated as described herein can be a child. For example, a human child that can be assessed and / or treated as described herein can be from about 1 year to about 12 years old. In some cases, a human having a CDG that can be assessed and / or treated as described herein can be an adolescent. For example, a human adolescent that can be assessed and / or treated as described herein can be from about 13 years to about 17 years of age. In some cases, a human having a CDG that can be assessed and / or treated as described herein can be an adult. For example, a human adult that can be assessed and / or treated as described herein can be at least 18 years of age. In another example, a human adult that can be assessed and / or treated as Attorney Docket No.07039-2225WO1 / 2023-182 described herein can be from about 18 years of age to about 100 years old. In some cases, a mammal (e.g., a human) that can be assessed and / or treated as described herein can be identified as having a CDG. Any appropriate method can be used to identify a mammal (e.g., a human) as having a CDG. In some cases, genetic diagnostics such as whole exome sequencing, mass spectrometry detection of carbohydrate-deficient transferrin (CDT), mass spectrometry-based analysis of serum / plasma-derived glycans, and / or testing for the enzymatic activity of the affected enzyme can be used to identify a mammal (e.g., a human) as having a CDG. A circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include any appropriate number of glycopeptides. For example, a circulating glycopeptide signature can include one or more (e.g., one, two, three, four, five, six, seven, eight, or more) glycopeptides. For example, a circulating glycopeptide signature can include from about 1 glycopeptide to about 8 glycopeptides (e.g., from 1 to 7, from 1 to 6, from 1 to 5, from 1 to 4, from 1 to 3, from 1 to 2, from 2 to 8, from 3 to 8, from 4 to 8, from 5 to 8, from 6 to 8, from 7 to 8, from 2 to 7, from 3 to 6, from 4 to 5, from 2 to 4, from 3 to 5, from 4 to 6, or from 5 to 7 glycopeptides). A circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include any appropriate one or more glycopeptides. A glycopeptide can include any appropriate polypeptide. Examples of polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, C4 polypeptides, ORM1 polypeptides, ORM2 polypeptides, F12 polypeptides, HP polypeptides, C7 polypeptides, transferrin polypeptides, complement C2 polypeptides, complement C3 polypeptides, fetuin polypeptides, attractin polypeptides, prothrombin (F2) polypeptides, albumin polypeptides, complement factor H polypeptides, complement factor I polypeptides, alpha-2-macroglobulin polypeptides, hemopexin polypeptides, alpha-1-antitrypsin polypeptides, galectin-3-binding protein polypeptides, and beta-2-glycoprotein-1 polypeptides. In some cases, a glycopeptide can include a peptide derived from a polypeptide described herein. For example, a circulating glycopeptide can be cleaved (e.g., enzymatically cleaved) to generate one or more glycopeptides and the generated glycopeptide(s) can be used to assess a mammal (e.g., a human) having a CDG as described herein. Attorney Docket No.07039-2225WO1 / 2023-182 In some cases, a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include a C4 polypeptide. In some cases, a C4 polypeptide can be a C4A polypeptide. In some cases, a C4 polypeptide can be a C4B polypeptide. Examples of C4 polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, polypeptides having an amino acid sequence set forth in the National Center for Biotechnology Information (NCBI) GenBank®or GenPept®databases at Accession Nos. NP_009224, NP_009224.2, NP_001002029, NP_001002029.3, and NP_000583. In some cases, a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include a ORM1 polypeptide. Examples of ORM1 polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, polypeptides having an amino acid sequence set forth in the NCBI GenBank®or GenPept®databases at Accession No. NP_000598. In some cases, a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include a ORM2 polypeptide. Examples of ORM2 polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, polypeptides having an amino acid sequence set forth in the NCBI GenBank®or GenPept®databases at Accession No. NP_000599. In some cases, a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include a F12 polypeptide. Examples of F12 polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, polypeptides having an amino acid sequence set forth in the NCBI GenBank®or GenPept®databases at Accession Nos. NP_000496 and NP_000496.2. In some cases, a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include a HP polypeptide. Examples of HP polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, polypeptides having an Attorney Docket No.07039-2225WO1 / 2023-182 amino acid sequence set forth in the NCBI GenBank®or GenPept®databases at Accession Nos. NP_005134 and NP_005134. In some cases, a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include a C7 polypeptide. Examples of C7 polypeptides that can be glycosylated and can be present in a circulating glycopeptide signature described herein include, without limitation, polypeptides having an amino acid sequence set forth in the NCBI GenBank®or GenPept®databases at Accession Nos. NP_000578, and NP_000578.2. A glycan that can be present on a glycopeptide in a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include any appropriate number of carbohydrate moieties. In some cases, a glycan that can be present on a glycopeptide in a circulating glycopeptide signature described herein can include from about 1 to about 50 carbohydrate moieties (e.g., from about 1 to about 40, from about 1 to about 30, from about 1 to about 25, from about 1 to about 20, from about 1 to about 15, from about 1 to about 12, from about 2 to about 40, from about 2 to about 30, from about 2 to about 25, from about 2 to about 20, from about 2 to about 15, from about 2 to about 12, from about 3 to about 40, from about 3 to about 30, from about 3 to about 25, from about 3 to about 20, from about 3 to about 15, from about 10 to about 40, from about 10 to about 30, from about 10 to about 20, from about 15 to about 35, or from about 3 to about 12 carbohydrate moieties). A glycan that can be present on a glycopeptide in a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include any appropriate carbohydrate moiety. In some cases, a glycan that can be present on a glycopeptide in a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include one or more hexose moieties. A hexose can be any appropriate hexose. Examples of hexoses include, without limitation, mannose, glucose, and galactose. In some cases, a glycan that can be present on a glycopeptide in a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can include one or more N-acetylhexosamine moieties. Examples of N- Attorney Docket No.07039-2225WO1 / 2023-182 acetylhexosamines include, without limitation, N-acetylgalactosamine, N-acetylglucosamine, and N-acetylmannosamine. A glycan that can be present on a glycopeptide in a circulating glycopeptide signature described herein can include any appropriate combination of carbohydrate moieties. In some cases, a glycan can include a single moiety of a particular carbohydrate. For example, a glycan can include a single hexose moiety (Hex1), such as a single mannose moiety (Man1). For example, a glycan can include a single N-acetylhexosamine moiety (HexNAc1), such as a single N-acetylglucosamine moiety (GlcNAc1). In some cases, a glycan can include two or more (e.g., two, three, four, five, six, seven, eight, or more) of a single carbohydrate moiety. For example, a glycan can include 4 hexose moieties (Hex4), such as 4 mannose moieties (Man4). In another example, a glycan can include 5 hexose moieties (Hex5), such as 5 mannose moieties (Man5). In yet another example, a glycan can include 6 hexose moieties (Hex6), such as 6 mannose moieties (Man6). For example, a glycan can include 2 N- acetylhexosamine moieties (HexNAc2), such as 2 N-acetylglucosamine moieties (GlcNAc2). In some cases, a glycan can include two or more (e.g., two, three, four, five, six, seven, eight, or more) different carbohydrate moieties. A glycan that can be present on a glycopeptide in a circulating glycopeptide signature that can be used to assess a mammal (e.g., a human) having a CDG as described herein can be any appropriate glycan. Examples of glycans that can be present on a glycopeptide that can be present in a circulating glycopeptide signature described herein include, without limitation, Hex1HexNAc2 (e.g., Man1GlcNAc2 and Gal1GlcNAc2), Hex2HexNAc2 (e.g., Man2GlcNAc2 and Gal2GlcNAc2), Hex3HexNAc2 (e.g., Man3GlcNAc2 and Gal3GlcNAc2), Hex4HexNAc2(e.g., Man4GlcNAc2and Gal4GlcNAc2), Hex5HexNAc2(e.g., Man5GlcNAc2and Gal5GlcNAc2), Hex6HexNAc2 (e.g., Man6GlcNAc2 and Gal6GlcNAc2), Hex5HexNAc4NeuAc2Fuc1 (e.g., Man5GlcNAc4NeuAc2Fuc1 and Gal5GlcNAc4NeuAc2Fuc1), Hex5HexNAc4NeuAc2(e.g., Man5GlcNAc4NeuAc2and Gal5GlcNAc4NeuAc2), Hex5HexNAc4NeuAc1 (e.g., Man5GlcNAc4NeuAc1 and Gal5GlcNAc4NeuAc1), Hex5HexNAc3NeuAc1 (e.g., Man5GlcNAc3NeuAc1 and Gal5GlcNAc3NeuAc1), Hex6HexNAc3NeuAc1(e.g., Man6GlcNAc3NeuAc1and Gal6GlcNAc3NeuAc1), and Hex6HexNAc3NeuAc1Fuc1(e.g., Man6GlcNAc3NeuAc1Fuc1and Gal6GlcNAc3NeuAc1Fuc1). Attorney Docket No.07039-2225WO1 / 2023-182 In some cases, a circulating glycopeptide signature used to determine whether or not a mammal (e.g., a human) having a CDG has PMM2-CDG as described herein can include an altered level (e.g., an elevated level or a decreased level) of one or more (e.g., one, two, three, four, five, six, seven, eight, or more) glycopeptides. For example, a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be assessed for the circulating glycopeptide signature to determine whether or not the mammal has PMM2- CDG. In some cases, an altered level of a glycopeptide in a circulating glycopeptide signature that can be used to identify a mammal (e.g., a human) having a CDG as having PMM2-CDG can be an elevated level. The term “elevated level” as used herein with respect to a level of a glycopeptide in a circulating glycopeptide signature described herein refers to any level that is higher than a reference level of the glycopeptide. In some cases, an elevated level of a glycopeptide can be a level that is at least 2 (e.g., about 3, about 4, about 5, about 10, about 20, about 25, about 30, about 40, about 50, or more) fold higher than a reference level of the glycopeptide. In some cases, an elevated level of a glycopeptide can be a level that is at least 10% (e.g., about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95%, or more) higher than a reference level of the glycopeptide. The term “decreased level” as used herein with respect to a level of a glycopeptide in a circulating glycopeptide signature described herein refers to any level that is lower than a reference level of the glycopeptide. In some cases, a decreased level of a glycopeptide can be a level that is at least 2 (e.g., about 3, about 4, about 5, about 10, about 20, about 25, about 30, about 40, about 50, or more) fold lower than a reference level of the glycopeptide. In some cases, a decreased level of a glycopeptide can be a level that is at least 10% (e.g., about 20%, about 30%, about 40%, about 50%, about 60%, about 70%, about 80%, about 90%, about 95% or more) lower than a reference level of the glycopeptide. The term “reference level” as used herein with respect to a level of a glycopeptide in a circulating glycopeptide signature described herein refers to the level of the glycopeptide typically observed in a control sample. Control samples are samples obtained from mammals not having a CDG (e.g., healthy mammals such as healthy humans). It will be appreciated that levels of glycopeptides from comparable samples are used when determining whether or Attorney Docket No.07039-2225WO1 / 2023-182 not a particular level is an altered level (e.g., an elevated level or a decreased level) of a glycopeptide. In some cases, a circulating glycopeptide signature can include an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide. For example, an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide can be an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide. In some cases, a circulating glycopeptide signature can include an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide. For example, an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide can be an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide and / or an elevated level of an ORM1 (Asn103: Gal1GlcNAc2) polypeptide. In some cases, a circulating glycopeptide signature can include an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide. For example, an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide can be an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide and / or an elevated level of an ORM2 (Asn103: Gal1GlcNAc2) polypeptide. In some cases, a circulating glycopeptide signature can include an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide. For example, an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide can be an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide and / or an elevated level of an F12 (Asn249: Gal1GlcNAc2) polypeptide. In some cases, a circulating glycopeptide signature can include an elevated level of a HP polypeptide that is glycosylated at Asn211(e.g., a HP Asn211: Hex5HexNAc4NeuAc2Fuc1polypeptide). For example, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide can be an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide. In some cases, a HP polypeptide that is glycosylated at Asn211(e.g., a HP Asn211: Man5GlcNAc4NeuAc2Fuc1polypeptide) is not glycosylated at Asn207. In some cases, a circulating glycopeptide signature can include an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide. For example, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide can be an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide. In some cases, a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide is not glycosylated at Asn207. In some cases, a circulating glycopeptide signature can include an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide. For example, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide can be an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc1) polypeptide. In Attorney Docket No.07039-2225WO1 / 2023-182 some cases, a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. In some cases, a circulating glycopeptide signature can include an elevated level of a HP polypeptide that is glycosylated at Asn207(e.g., a HP Asn207: Hex5HexNAc4NeuAc2Fuc1HP some cases, a glycopeptide signature can include an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. For example, an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide can be an elevated level of a C7 (Asn202: Man3GlcNAc2) polypeptide. In some cases, a circulating glycopeptide signature can include an altered level (e.g., an elevated level or a decreased level) of one or more glycopeptides described in Example 1 and / or Example 2. In some cases, a circulating glycopeptide signature can include an altered level (e.g., an elevated level or a decreased level) of one or more glycopeptides set forth in Table 3. In some cases, a circulating polypeptide signature can include an altered level (e.g., an elevated level or a decreased level) of one or more glycopeptides which lack glycosylation at one or more particular amino acid sites (e.g., one or more non-glycosylated polypeptides) that are typically glycosylated in mammals not having a CDG (e.g., healthy mammals such as healthy humans). In some cases, a circulating glycopeptide signature can include an elevated level of a C4 (Asn226: non-glycosylated) polypeptide. In some cases, a circulating glycopeptide signature can include an elevated level of a TF (Asn432: non-glycosylated) polypeptide. In some cases, a circulating glycopeptide signature can include an elevated level of a TF (Asn630: non-glycosylated) polypeptide. Any appropriate method can be used to determine the presence, absence, or level of a glycopeptide described herein. Exemplary methods that can be used to determine the presence, absence, or level of a glycopeptide described herein in a sample (e.g., a blood sample) include, without limitation, TMT-based discovery glycoproteomics, label-free discovery glycoproteomics with or without enrichment of glycopeptides, targeted analysis of glycopeptides including parallel reaction monitoring, multiple reaction monitoring, and selective reaction monitoring. Attorney Docket No.07039-2225WO1 / 2023-182 Any appropriate sample from a mammal (e.g., a human) having a CDG (e.g., PMM2- CDG) can be assessed as described herein (e.g., to determine the circulating glycopeptide signature of the mammal). In some cases, a sample can be a biological sample. In some cases, a sample can contain one or more biological molecules (e.g., one or more glycopeptides). In some cases, a sample can be a blood sample. For example, a blood sample can be a whole blood sample, a plasma sample, or a serum sample. A biological sample can be a fresh sample, a frozen sample, or a fixed sample. In some cases, a biological sample can be processed to isolate or extract one or more biological molecules. For example, a sample can be processed to obtain a sample of circulating glycopeptides, which can be assessed for the presence, absence, or level of one or more glycopeptides as described herein. In some cases, the circulating glycopeptide signature of a mammal having a CDG can be used to identify the mammal as having PMM2-CDG. For example, a mammal (e.g., a human) having a CDG can be identified as having PMM2-CDG based, at least in part, on the presence of a circulating glycopeptide signature of a sample (e.g., a blood sample) obtained from the mammal. In some cases, the presence of one or more of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having PMM2-CDG. For example, the presence of one or more of (1) an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Attorney Docket No.07039-2225WO1 / 2023-182 Man3GlcNAc2) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having PMM2-CDG. In some cases, the circulating glycopeptide signature of a mammal having PMM2- CDG can include a decreased level of one or more glycosylated albumin polypeptides. Examples of glycosylated albumin polypeptides that can be decreased in the circulating glycopeptide signature of a mammal having PMM2-CDG include, without limitation, albumin (Asn123: Hex5HexNAc4NeuAc2) polypeptides, albumin (Asn123: Hex5HexNAc4NeuAc1) polypeptides, and albumin (Asn123: Hex5HexNAc4) polypeptides. In some cases, the circulating glycopeptide signature of a mammal having a CDG can be used to identify the mammal as having a CDG that is not PMM2-CDG. For example, a mammal (e.g., a human) having a CDG can be identified as having a CDG that is not PMM2- CDG based, at least in part, on a circulating glycopeptide signature of a sample (e.g., a blood sample) obtained from the mammal (e.g., a human). In some cases, the absence of each of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide in a sample obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having a CDG that is not PMM2- CDG. For example, the absence of each of (1) an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Man3GlcNAc2) polypeptide in a sample obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having a CDG that is not PMM2-CDG. Attorney Docket No.07039-2225WO1 / 2023-182 In some cases, a mammal (e.g., a human) having a CDG that is assessed as described herein (e.g., to determine the circulating glycopeptide signature of the mammal) can be treated using one or more treatments that are selected based, at least in part, on the presence or absence of the circulating glycopeptide signature of the mammal as described herein. In general, a treatment and / or intervention for CDG can include dietary supplementation to improve polypeptide glycosylation (e.g., administration of monosaccharides or derivatives thereof), organ transplantation to replace a failing organ (e.g., liver transplant), administration of one or more agents (e.g., epalrestat and / or acetazolamide), administration of one or more pharmacological chaperones, and / or enzyme replacement therapy (e.g., administration of a functional polypeptide (or nucleic acid encoding a functional polypeptide) of the deficient polypeptide associated with the CDG). In some cases, a mammal (e.g., a human) having a CDG that is identified as having PMM2-CDG as described herein (e.g., based, at least in part, on the presence of the circulating glycopeptide signature) can be selected to receive a PMM2-CDG treatment. For example, a mammal having a CDG and having a circulating glycopeptide signature that includes the presence of one or more of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide can be selected to receive a PMM2-CDG treatment. For example, a mammal having a CDG and having a circulating glycopeptide signature that includes the presence of one or more of (1) an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Attorney Docket No.07039-2225WO1 / 2023-182 Man5GlcNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Man3GlcNAc2) polypeptide can be selected to receive a PMM2-CDG treatment. In some cases, a mammal (e.g., a human) having a CDG that is identified as having a CDG that is not PMM2-CDG as described herein (e.g., based, at least in part, on the circulating glycopeptide signature of the mammal) can be selected to receive an alternative treatment (e.g., a CDG treatment that is not a PMM2-CDG treatment). For example, a mammal having a CDG and having a circulating glycopeptide signature that lacks each of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide can be selected to receive an alternative treatment (e.g., a CDG treatment that is not a PMM2-CDG treatment). For example, a mammal having a CDG and having a circulating glycopeptide signature that lacks each of (1) an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Man3GlcNAc2) polypeptide can be selected to receive an alternative treatment (e.g., a CDG treatment that is not a PMM2-CDG treatment). This document also provides methods for treating a mammal (e.g., a human) having a CDG. In some cases, a mammal (e.g., a human) having a CDG that is assessed as described herein (e.g., to determine the circulating glycopeptide signature of the mammal) can be administered or instructed to self-administer one or more (e.g., one, two, three, four, five, or more) treatments and / or interventions effective to treat the CDG. For example, a mammal (e.g., a human) having a CDG and assessed as described herein can be administered or instructed to self-administer one or more treatments and / or interventions that are selected Attorney Docket No.07039-2225WO1 / 2023-182 based, at least in part, on the presence or absence of the circulating glycopeptide signature of the mammal. When treating a mammal (e.g., a human) having a CDG and identified as having PMM2-CDG as described herein (e.g., based, at least in part, on the presence of a circulating glycopeptide signature), the mammal can be administered or instructed to self-administer one or more treatments and / or interventions effective to treat PMM2-CDG (e.g., a PMM2-CDG treatment). In some cases, a mammal (e.g., a human) having a CDG and having a circulating glycopeptide signature that includes the presence of one or more of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide can be administered or instructed to self-administer one or more PMM2-CDG treatments. For example, a mammal (e.g., a human) having a CDG and having a circulating glycopeptide signature that includes the presence of one or more of (1) an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Man3GlcNAc2) polypeptide can be administered or instructed to self-administer one or more PMM2-CDG treatments. A mammal having a CDG and identified as having PMM2-CDG as described herein (e.g., based, at least in part, on the presence of a circulating glycopeptide signature) can be selected to receive, can be administered, or can be instructed to administer any appropriate treatments and / or interventions effective to treat PMM2-CDG. In some cases, PMM2-CDG treatment can include, without limitation, administering a PMM2 polypeptide (or nucleic acid encoding a PMM2 polypeptide). Examples of PMM2 polypeptides and nucleic acids Attorney Docket No.07039-2225WO1 / 2023-182 encoding a PMM2 polypeptide can be as described in Example 4. In some cases, a PMM2 polypeptide (or nucleic acid encoding a PMM2 polypeptide) can be as set forth in the NCBI GenPept®databases at Accession no. NP_000294.1. Any appropriate method can be used to administer a PMM2 polypeptide (or nucleic acid encoding a PMM2 polypeptide to a mammal (e.g., a human) in need thereof (e.g., a mammal such as a human identified as having PMM2-CDG as described herein). For example, a PMM2 polypeptide or a variant of the PMM2 polypeptide with one or more (e.g., e.g., one, two, three, four, five, six, seven, eight, nine, ten, or more) amino acid deletions, additions, substitutions, or combinations thereof, provided that the variant retains the function of the naturally-occurring PMM2 polypeptide can be administered to a mammal (e.g., a human) in need thereof. For example, a nucleic acid encoding a PMM2 polypeptide can be administered to a mammal (e.g., a human) in need thereof. When a nucleic acid encoding a PMM2 polypeptide is administered to a mammal (e.g., a human) in need thereof, the nucleic acid can be in the form of a vector (e.g., an expression plasmid or a viral vector such as an adeno-associated virus (AAV) vector). A vector (e.g., an expression plasmid or viral vector) including nucleic acid encoding a PMM2 polypeptide also can include any appropriate promoter and other regulatory sequence (e.g., transcription and translation initiation and termination codons) operably linked to the nucleic acid encoding the PMM2 polypeptide. In some cases, a promoter used to drive expression can be a constitutive promotor or a regulatable promotor. Examples of promotors that can be used as described herein include, without limitation, cytomegalovirus (CMV) promoters (e.g., immediate early CMV promoters) and beta-actin promoters. In some cases, a PMM2-CDG treatment can include, without limitation, administering one or more gene therapy components designed to correct an endogenous nucleic acid encoding a deficient PMM2 polypeptide (e.g., to correct a pathogenic PMM2 gene variant such as the PMM2 gene variant set forth in the NCBI GenBank®database at Accession no. NG_009209.1). In some cases, a PMM2-CDG treatment can include, without limitation, administering one or more antisense oligonucleotides (ASO) designed to decrease expression an endogenous nucleic acid encoding a deficient PMM2 polypeptide (e.g., to decrease a level of the deficient PMM2 polypeptide). Attorney Docket No.07039-2225WO1 / 2023-182 In some cases, a PMM2-CDG treatment can include, without limitation, administering epalrestat and / or one or more monosaccharides and / or one or more monosaccharide derivatives. For example, a mammal having a CDG and identified as having PMM2-CDG as described herein (e.g., based, at least in part, on the presence of a circulating glycopeptide signature) can be selected to receive, can be administered, or can be instructed to administer a PMM2 polypeptide (or nucleic acid encoding a PMM2 polypeptide) together with epalrestat. For example, a mammal having a CDG and identified as having PMM2-CDG as described herein (e.g., based, at least in part, on the presence of a circulating glycopeptide signature) can be selected to receive, can be administered, or can be instructed to administer a PMM2 polypeptide (or nucleic acid encoding a PMM2 polypeptide) together with one or more monosaccharides and / or one or more monosaccharide derivatives. When treating a mammal (e.g., a human) having a CDG and identified as having a CDG that is not PMM2-CDG as described herein (e.g., based, at least in part, on the circulating glycopeptide signature), the mammal can be administered or instructed to self- administer one or more alternative treatments and / or interventions (e.g., one or more treatments and / or interventions that are effective to a treat a CDG that is not PMM2-CDG). In some cases, a mammal (e.g., a human) having a CDG and having a circulating glycopeptide signature that lacks each of (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide can be administered or instructed to self-administer one or more alternative treatments. For example, a mammal (e.g., a human) having a CDG and having a circulating glycopeptide signature that lacks each of (1) an elevated level of a C4 (Asn226: Man5GlcNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Man1GlcNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Man1GlcNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Man1GlcNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Attorney Docket No.07039-2225WO1 / 2023-182 Man5GlcNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Man5GlcNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Man3GlcNAc2) polypeptide can be administered or instructed to self-administer one or more alternative treatments. A mammal having a CDG and identified as having a CDG that is not PMM2-CDG as described herein (e.g., based, at least in part, on the circulating glycopeptide signature) can be selected to receive, can be administered, or can be instructed to administer any appropriate alternative treatments and / or interventions (e.g., one or more treatments and / or interventions that are effective to a treat a CDG that is not PMM2-CDG). In some cases, an alternative treatment can include, without limitation, administering one or more monosaccharides and / or monosaccharide derivatives. Examples of monosaccharides and / or monosaccharide derivatives that can be included in an alternative treatment include, without limitation, galactose, mannose, and mannose-1-phosphate. In some cases, an alternative treatment can include administering one or more agents that can be used to treat one or more symptoms of CDG that is not PMM2-CDG (e.g., one or more anticonvulsants). Examples of agents that can be used to treat one or more symptoms of CDG that is not PMM2-CDG include, without limitation, aldose reductase inhibitors, acetazolamide, and epalrestat. In some cases, an alternative treatment can include, without limitation, enzyme replacement therapy (e.g., administering a functional polypeptide (or nucleic acid encoding a functional polypeptide) that is deficient in a mammal having CDG that is not PMM2-CDG). For example, a functional phosphatidylinositol N-acetylglucosaminyltransferase subunit A (PIGA) polypeptide (or nucleic acid encoding a functional PIGA polypeptide) can be administered to a mammal having a PIGA-CDG, a functional steroid 5-alpha-reductase 3 (SRD5A3) polypeptide (or nucleic acid encoding a functional SRD5A3 polypeptide) can be administered to a mammal having a CRD5A3-CDG, a functional glucosamine (UDP-N- acetyl)-2-epimerase (GNE) polypeptide (or nucleic acid encoding a functional GNE polypeptide) can be administered to a mammal having GNE-CDG, and a functional mannose phosphate isomerase (MPI) polypeptide (or a nucleic acid encoding a functional MPI polypeptide) can be administered to a mammal having MPI-CDG. In some cases, the methods and materials provided herein can be used to identify a mammal as having a CDG other than PMM2-CDG. In some cases, a circulating glycopeptide Attorney Docket No.07039-2225WO1 / 2023-182 signature of a mammal (e.g., a human) having a CDG can be used to identify that mammal as having MPI-CDG, selecting a treatment for that mammal, and / or treating that mammal. For example, a mammal (e.g., a human) having a CDG can be identified as having MPI-CDG based, at least in part, on the presence of a circulating glycopeptide signature of a sample (e.g., a blood sample) obtained from the mammal. For example, the presence of one or more of (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide, (2) an elevated level of an alpha-2-HS- glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide, (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide, and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having MPI- CDG. For example, the presence of one or more of (1) an elevated level of an IGHG2 (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide, (2) an elevated level of an AHSG (Asn176:Hex6HexNAc3NeuAc1) polypeptide, (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide, and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having MPI- CDG. In some cases, a circulating glycopeptide signature shown in Figures 9A and 9B and / or in Example 2 can be used to identify a mammal as having MPI-CDG. In some cases, a mammal identified as having MPI-CDG can selected to a receive a MPI-CDG treatment and, optionally, can be administered a MPI-CDG treatment. For example, a mammal identified as having MPI-CDG as described herein can be selected to receive, and optionally administered, a MPI polypeptide (or nucleic acid encoding the MPI polypeptide). Examples of MPI polypeptides and nucleic acid encoding an MPI polypeptide can be as shown in Example 4. In some cases, a circulating glycopeptide signature of a mammal (e.g., a human) having a CDG can be used to identify that mammal as having SRD5A3-CDG, selecting a treatment for that mammal, and / or treating that mammal. For example, a mammal (e.g., a human) having a CDG can be identified as having SRD5A3-CDG based, at least in part, on the presence of a circulating glycopeptide signature of a sample (e.g., a blood sample) obtained from the mammal. In some cases, the presence of one or more of (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide, (2) an Attorney Docket No.07039-2225WO1 / 2023-182 elevated level of an alpha-2-macroglobulin (?2M) (Asn869:Hex3HexNAc2) polypeptide, (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide, and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having SRD5A3-CDG. For example, the presence of one or more of (1) an elevated level of an apoB100 (Asn3465:Hex3HexNAc3) polypeptide, (2) an elevated level of an ?2M (Asn869:Hex3HexNAc2) polypeptide, (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide, and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having SRD5A3-CDG. In some cases, a HP polypeptide that is glycosylated at Asn211(Asn211:Hex4HexNAc3NeuAc1) is not glycosylated at Asn207. In some cases, the circulating glycopeptide signature of a mammal having SRD5A3-CDG can include a decreased level of one or more glycosylated albumin polypeptides. Examples of glycosylated albumin polypeptide that can be decreased in the circulating glycopeptide signature of a mammal having SRD5A3-CDG include, without limitation, albumin (Asn123: Hex5HexNAc4NeuAc1) polypeptides and albumin (Asn123: Hex4HexNAc3NeuAc1) polypeptides. In some cases, a circulating glycopeptide signature shown in Figures 10A and 10B, Figure 12B, and / or in Example 2 can be used to identify a mammal as having SRD5A3-CDG. In some cases, a mammal identified as having SRD5A3-CDG can selected to a receive a SRD5A3-CDG treatment and, optionally, can be administered a SRD5A3-CDG treatment. For example, a mammal identified as having SRD5A3-CDG as described herein can be selected to receive, and optionally administered, a SRD5A3 polypeptide (or nucleic acid encoding the SRD5A3 polypeptide). Examples of SRD5A3 polypeptides and nucleic acid encoding a SRD5A3 polypeptide can be as shown in Example 4. In some cases, a circulating glycopeptide signature of a mammal (e.g., a human) having a CDG can be used to identify that mammal as having MAN1B1-CDG, selecting a treatment for that mammal, and / or treating that mammal. For example, a mammal (e.g., a human) having a CDG can be identified as having MAN1B1-CDG based, at least in part, on the presence of a circulating glycopeptide signature of a sample (e.g., a blood sample) obtained from the mammal. In some cases, the presence of one or more of (1) an elevated Attorney Docket No.07039-2225WO1 / 2023-182 level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) polypeptide, (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide, (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide, and (4) an elevated level of a C4B-binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having MAN1B1-CDG. For example, the presence of one or more of (1) an elevated level of an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide, (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide, (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide, and (4) an elevated level of a C4B- binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide in a sample (e.g., a blood sample) obtained from a mammal (e.g., a human) having a CDG can be used to identify that mammal as having MAN1B1-CDG. In some cases, the circulating glycopeptide signature of a mammal having MAN1B1-CDG can include an elevated level of one or more glycosylated albumin polypeptides. Examples of glycosylated albumin polypeptide that can be elevated in the circulating glycopeptide signature of a mammal having MAN1B1-CDG include, without limitation, albumin (Asn123: Hex6HexNAc3NeuAc1) polypeptides. In some cases, a circulating glycopeptide signature shown in Figures 11A and 11B, Figure 12C, and / or in Example 2 can be used to identify a mammal as having MAN1B1-CDG. In some cases, a mammal identified as having MAN1B1-CDG can selected to a receive a MAN1B1- CDG treatment and, optionally, can be administered a MAN1B1-CDG treatment. For example, a mammal identified as having MAN1B1-CDG as described herein can be selected to receive, and optionally administered, a MAN1B1 polypeptide (or nucleic acid encoding the MAN1B1 polypeptide). Examples of MAN1B1 polypeptides and nucleic acid encoding a MAN1B1 polypeptide can be as shown in Example 4. In some cases, when treating a mammal (e.g., a human) having a CDG as described herein, the treatment can be effective to reduce or eliminate one or more symptoms of a CDG. Symptoms of a CDG include, without limitation, hypotonia (low muscle tone), failure to thrive (slow growth), developmental delay, hepatopathy (liver disease) presenting as elevated liver enzymes (ALT and AST), coagulopathy (bleeding tendencies early on and abnormal clotting as adults), esotropia (crossed eyes), seizures, cerebellar hypoplasia Attorney Docket No.07039-2225WO1 / 2023-182 (changes in the brain that can be seen on brain imaging), ataxia (poor balance and movement coordination), dysarthria (slurred speech), absent puberty in females, retinitis pigmentosa (pigment in back of the eye), progressive scoliosis (curvature of the spine), and joint contractures. In some cases, the methods and materials described herein can be used to reduce one or more symptoms of CDG present within a mammal having a CDG by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, the methods and materials described herein can be used to reduce one or more symptoms of CDG present within a mammal having a CDG by, for example, 10, 20, 30, 40, 50, 60, 70, 80, 90, 95, or more percent. In some cases, when treating a mammal (e.g., a human) having a CDG (e.g., PMM2- CDG) as described herein, the treatment can be effective to extend the life expectancy of the mammal receiving the treatment compared to a mammal having a CDG (e.g., PMM2-CDG) and not receiving that treatment. In some cases, the methods and materials described herein can be used to extend the life expectancy of the mammal receiving the treatment by, for example, at least 1 month (e.g., 6 months, 1 year, 1.5 years, 2 years, 3 years or more.). In some cases, the methods and materials described herein can be used to extend the life expectancy of the mammal receiving the treatment by, for example, 1, 2, 3, 4, 5, 6, 7, 8, 9, 10 or more percent. In some cases, when treating a mammal (e.g., a human) having a CDG (e.g., PMM2- CDG) as described herein, the treatment can be effective to decrease the mammal’s Nijmegen pediatric CDG rating scale (NPCRS) score. The NPCRS is based around three domains, with each domain containing specific items relevant to the assessment of CDG patients. The three domains are as follows: Section I (Current Function) is a domain consisting of five questions regarding five general functions (vision, hearing, communication, feeding and mobility); Section II (System Specific Involvement) includes questions directly assessing CNS, blood, gastrointestinal, endocrine, respiratory, cardiovascular, renal and liver function over the preceding 6 months; and Section III (Current Clinical Assessment) includes questions related to status. For each item, there are four possible responses reflecting normal (0), mild (1), moderate (2), and severe (3) impairment, with one exception in the form of a flow chart to assess developmental progress for which a score of 0–7 is possible. Domain scores are added up and are used to scale patients into a Attorney Docket No.07039-2225WO1 / 2023-182 mild (0–14 points), moderate (15–25 points) and severe (>26 points) category. See, for example, Achouitar et al., J. Inherit. Metab. Dis.34:923–927 (2011). In some cases, the methods and materials described herein can be used to decrease the NPCRS score of the mammal receiving the treatment by, for example, at least 1 point (e.g., 2, 3, 4, 5, 6, 7, or more points). In some cases, the methods and materials described herein can be used to decrease the NPCRS score of the mammal receiving the treatment by, for example, a category (e.g., from the severe category to the moderate category, or from the moderate category to the mild category). The invention will be further described in the following examples, which do not limit the scope of the invention described in the claims. EXAMPLESExample 1: A Glycopeptide Signature of PMM2-CDG. Current methods for diagnosing PMM2-CDG rely on whole exome sequencing and / or a screening test for secretory N-linked glycosylation of intact transferrin for carbohydrate- deficient transferrin (CDT). Results of such diagnostic tests are frequently unclear due to the presence of variants of uncertain significance in nucleic acid sequences that encode a PMM2 polypeptide (e.g., a PMM2 gene). This Example describes the identification of circulating glycopeptides that were secreted by cells of organs affected by PMM2-CDG. Such circulating glycopeptides can be used as markers to identify a mammal (e.g., a human) as having PMM2-CDG. METHODS Study design To determine alterations in the circulating glycopeptides of individuals with PMM2- CDG, and to identify sensitive biomarkers for this disorder that could be used for diagnosis and monitoring of treatment response, thirty-five affected individuals were recruited and their serum samples collected as described in ensuing paragraphs. Unaffected age- and sex- matched individuals were recruited and their serum was collected for use as controls. The experimental design was of controlled laboratory experiments. The measurement methods Attorney Docket No.07039-2225WO1 / 2023-182 employed mass spectrometry, specifically, glycopeptide abundance in samples from affected individuals using Tandem Mass Tag (TMT) label reporter ion intensity, or label-free precursor ion peak intensity depending on the experimental step. Samples from individuals with PMM2-CDG and matched control sets (total 14 samples) were studied by TMT-based deep glycoproteomic methods for discovery of glycopeptide alterations (Table 1, discovery set). An independent set of 42 samples were studied using a single mass spectrometry run per sample following glycopeptide enrichment using MAX cartridges (Table 1, profiling set) to confirm findings from the discovery set and to design a targeted assay for selected glycopeptides. A final set of 16 samples including randomized matched case-controls, was used to test the newly developed targeted assay in a blinded fashion (Table 1, blinded set). This targeted assay led to the identification of particular glycopeptides as biomarkers for PMM2-CDG. Affected individuals Thirty-six samples from thirty-five affected individuals with a molecularly confirmed diagnosis of PMM2-CDG were included in the study. Data was collected prospectively, and retrospective data was available for most affected individuals as well. Table 1 includes a list of included subjects with PMM2-CDG with demographic and genetic information, and clinical and biochemical findings including results of intact mass analysis testing for CDT and results of glycopeptide analysis for C4 glycopeptide (Asn226Man5GlcNAc2).

[0002] Attorney Docket No.07039-2225WO1 / 2023-182 Table 1. Affected individuals and their clinical and laboratory features. The NijmegenlProgressionacisesignCDG Rating Neurologicni2elelnoCDT by intact masssictrometryl ra6) smtomslcMlad m s ee22nsAta c2A N xeH n5aM edededededededededededededededededed ededed Attorney Docket No.07039-2225WO1 / 2023-182 Sample Absence of neuropath Y229S / 2211 F 5 1 4 10 +, # -y / able+ 0.79 (?) 0.376 (?) Detectedto walkT237Rededededed ed edededededededed M: male; F: female. NPCRS: Nijmegen progression CDG rating scale. Patients are scored on three sections as follows: section I (current function, 21 points), section II (system-specific involvement, 30 points) and section III (current clinical assessment, 31 points) for a total score of 82 points; using these scores, patients are scaled into mild (0–14), moderate (15–25) or severe (>26) categories. GDD: global developmental delay. “+”: present. “-”: absent. “#”: learning disability without intellectual disability. Subjects corresponding to three samples had non-coding pathogenic variants in their second allele: sample 18, IVS3+2T>C; samples 27 and 28, c.640- 23A>G. CDT: carbohydrate-deficient transferrin analysis by mass spectrometry of immunopurified intact transferrin. Drug administration Epalrestat was administered orally to an affected individual (corresponding to samples 3 and 15), 3 times per day (tid) before meals in a divided dose (0.8 mg / kg / day; 5 mg tid) (Ono Pharmaceuticals, Osaka, Japan) between day 1 and day 180 of the study. See, for example, Ligezka et al., Ann. Neurol.90, 887-900 (2021). Attorney Docket No.07039-2225WO1 / 2023-182 Controls Thirty-six control serum samples were used from unaffected individuals, between the age of 1-36 (mean 12) years (22 males and 14 females) who donated deidentified residual samples (Table 2). Table 2. Demographics of unaffected controls. Analysis Set ID Age (years) Sex Attorney Docket No.07039-2225WO1 / 2023-182 Control 27 11 F Control 28 9 M Data extraction Clinical data was collected and extracted from the electronic clinical files and electronic laboratory data system. The Nijmegen Progression CDG Rating Scale (NPCRS) was used to assess disease severity. The NPCRS rating was performed in every affected individual at the time of the laboratory sample collection. The NPCRS is a clinical tool developed to determine the clinical severity and disease progression of individuals affected with CDG in an objective way and is validated for all age groups. Depending on the NPCRS score, individuals were scaled in a mild (0–14), moderate (15–25) and severe (>26) category (24-26). CDT analysis was performed by mass spectrometry analysis of intact transferrin. Mono-oligo / di-oligo and A-oligo / di-oligo ratios of glycosylated transferrin were collected for each affected individual. See, for example, Biffi et al., Clin. Biochem.40, 1431-1434 (2007) and Magalhaes et al., J. Pediatr. (Rio J) 96, 710-716 (2020). Serum protein digestion Bicinchoninic acid (BCA) protein assay was used to determine protein concentration of serum samples. Equal amount of total protein from each serum sample was vacuum-dried and reconstituted in 8 molar (M) Urea in 50 mM triethylammonium bicarbonate (TEAB), pH 8.5. Proteins were reduced by incubation with dithiothreitol at a final concentration of 10 mM (Sigma) at 37 °C for 45 minutes. Samples were then cooled to room temperature and alkylated by incubation with 40 millimolar (mM) iodoacetamide (Sigma) for 15 minutes in Attorney Docket No.07039-2225WO1 / 2023-182 the dark at room temperature. The samples were diluted with 50 mM TEAB to a final urea concentration of <1M and digestion was carried out with trypsin (Worthington, TPCK treated) at a ratio of 1:20 (trypsin:total protein) at 37 °C overnight. Tandem Mass Tag (TMT) labeling of peptides and glycopeptide enrichment using size- exclusion chromatography Peptides derived from serum samples of affected individuals (n=7) and controls (n=7) were labeled with tandem mass tag (TMTPro, Thermo Fisher) reagents as per the manufacturer’s instructions. Samples were pooled and the sample split into two aliquots for glycoproteomics and total proteomics experiments. About 90% of dried peptides were resuspended in 100 microliter (?L) of 0.1% formic acid and loaded onto Superdex peptide 10 / 300 column (GE Healthcare) for size-exclusion chromatography (SEC). Isocratic flow with 0.1% formic acid was used and 48 fractions were collected over a run time of 130 minutes. Early fractions from SEC collected over 55 minutes starting at 40 minutes after injection were selected based on the UV profile (214 nanometer (nm), 220 nm) and used for LC-MS / MS. The remaining aliquot (about 10%) of total peptides was cleaned up by C18 TopTips (Glygen) and fractionated by basic reversed phase liquid chromatography (bRPLC) on a C18 column (4.6 × 100 milllimeter (mm) column) using an Ultimate 3000 UHPLC System for the total proteomics experiment.5 mM ammonium formate in water, pH 9 and 5 mM ammonium formate in 90% acetonitrile, pH 9 were used as solvent A and B, respectively. Ninety-six fractions collected over 120 minutes were concatenated into 12 fractions. These fractions were dried down in a speed vacuum system and re-suspended in 0.1% formic acid for LC-MS / MS analysis. Enrichment of glycopeptides using mixed anion-exchange extraction cartridges For analysis of the profiling and blinded sets, glycopeptides were enriched from peptide samples using OASIS mixed anion-exchange cartridges (MAX, Waters). See, for example, Yang et al, Anal. Chem.89, 11193-11197 (2017). The MAX cartridges were conditioned with acetonitrile (ACN) thrice, then thrice with 100 mM triethylammonium acetate buffer, followed by thrice with water, and finally thrice with 95% ACN / 1% trifluoroacetic acid (TFA). Dried tryptic peptides from sera of affected individuals and controls were Attorney Docket No.07039-2225WO1 / 2023-182 reconstituted in 95% ACN / 1% TFA. Equal peptide amounts (400 micrograms (µg)) from each sample were used for loading thrice onto the cartridges. The cartridge was then washed thrice with 95% ACN / 1% TFA. Glycopeptides were eluted with 50% ACN / 0.1% TFA and dried down. The enriched glycopeptides from 17 affected individuals (sample 3 and samples 8 to 24) and 17 matched control serum samples were used for validation experiments using single run non-targeted analysis. For development and testing of the targeted glycopeptide assay, 16 samples from affected individuals (samples 21 to 36) and 16 matched control samples enriched using MAX cartridges were analyzed using parallel reaction monitoring (PRM)-based targeted analysis. LC-MS / MS analysis for discovery and profiling experiments LC-MS / MS parameters used were as described elsewhere. See, for example, Zhao et al., Cell Host Microbe 28, 586-601 e586 (2020); Saraswat et al., Mol. Omics.17, 939-947 (2021); and Budhraja et al, J. Inherit. Metab. Dis.46, 76-91 (2023). Briefly, for the TMT- based experiments, 11 early fractions from SEC and 12 concatenated fractions from bRPLC were analyzed by Orbitrap Exploris 480 mass spectrometer (Thermo Fisher Scientific) for glycoproteomics and proteomics, respectively. Peptides were separated by liquid chromatography on an EASY-Spray column (75 micrometer (µm) × 50 centimeter (cm), PepMap RSCL C18, Thermo Fisher Scientific) packed with 2 ?m C18 particles, and were maintained at 50 °C.0.1% formic acid in water (solvent A; sol A) and 0.1% formic acid in acetonitrile (solvent B; sol B) were used as solvents. Peptides were trapped on a trap column (100 millimeter (mm) × 2 cm, Acclaim PepMap100 Nano-Trap, Thermo Fisher Scientific) at a flow rate of 20 microliters per minute (µL / min). LC separation was performed at a flow rate of 300 nanoliters per minute (nL / min) and the following gradient was used: equilibration at 3% solvent B from 0 to 4 minutes, 3% to 10% sol B from 4 to 10 minutes, 10% to 35% sol B from 10.1 to 125 minutes, 35% to 80% sol B from 125 to 145 minutes followed by equilibration for next run at 5% sol B for 5 minutes. TMT-based experiments were done in DDA mode with top 15 ions isolated at a window of 0.7 m / z and default charge state of +2. Precursors with charge states ranging from +2 to +7 were considered for MS / MS events. Normalized stepped collision energy was applied to fragment precursors at energies of 15, 25, 40% for glycoproteomics and of 34% for proteomics. Precursor ions were acquired in the Attorney Docket No.07039-2225WO1 / 2023-182 Orbitrap mass analyzer in m / z range of 350-2,000 for glycoproteomics and 350-1,800 for proteomics at a resolution of 120,000 (at m / z 200). Automatic gain control for MS and MS / MS were 106and 1x105and injection time to reach AGC were 50 ms and 250 ms respectively. Exclude isotopes feature was set to “on” and 60 second dynamic exclusion was applied. Data acquisition was performed with option of “lock mass” (m / z 441.12002) for all data. MAX-enriched glycopeptides were analyzed on an Orbitrap Eclipse mass spectrometer connected to Ultimate 3000 liquid chromatography system (Thermo Fisher Scientific Inc., MA). Glycopeptides were trapped on a trap column (100 mm × 2 cm, Acclaim PepMap100 Nano-Trap, Thermo Fisher Scientific) at a flow rate of 20 µL / min. LC separation was performed on an analytical column (EasySpray 75 µm x 50 cm, C182 µm, 100 Å, (Thermo Fisher Scientific Inc., MA) with a flow rate of 300 nL / min with a linear gradient of solvent B (100% ACN, 0.1% formic acid) over a 150-minute gradient. All label- free experiments were done in data-dependent acquisition (DDA) mode at an isolation window of 1.6 m / z and default charge state of +2. Precursor ions were acquired at a resolution of 120,000 (at m / z 200) and at a resolution of 30,000 (at m / z 200) for fragment ions. Precursor fragmentation was carried out using normalized stepped higher-energy collisional dissociation (HCD) at 15, 25 and 40%. The scans were acquired in top-speed method with 3 second cycle time between MS and MS / MS. Database searching, data analysis and statistics Database searching was performed using pGlyco Version 2.2.0; and pGlyco version 3.0 was used to search for glycosylation at multiple glycosylation sites. See, for example, Zeng et al., Nat Methods 18, 1515-1523 (2021) and Liu et al., Nat Commun 8, 438 (2017). Glycan databases already available with the software were used and Uniprot Human Reviewed protein sequences (20,432 entries, downloaded February 1, 2021) were used as proteins sequence FASTA file. Fully tryptic cleavage specificity with 2 missed cleavages was used and precursor and fragment tolerance were set to 10 and 20 parts per million (ppm) respectively. Carbamidomethylation of cysteine was set as fixed modification and oxidation of methionine as a variable modification. For TMT-based experiments, TMTPro at lysine was set as a fixed modification and TMTPro at peptide N-terminal was set as variable Attorney Docket No.07039-2225WO1 / 2023-182 modification. The results were filtered to retain entries which had 5% false discovery rate (FDR) at the glycopeptide level. Reporter ion quantitation was performed on Proteome Discoverer 2.5 (reporter ion quantifier node) and IDs were matched with quantitation on a scan-to-scan (MS / MS) basis. Peptide-spectrum matches (PSMs) for glycopeptides were combined to reflect unique glycopeptides per search by glycan composition and peptide sequence and summed-up reporter ion intensities were calculated. Spectra were manually verified for several glycan oxonium ions and quality. All sialic acid glycopeptides’ spectra were verified for presence of sialic acid-specific oxonium ions at m / z 274.09, 292.10 and / or 657.23. Multiply glycosylated glycopeptides were verified for evidence of glycosylation (peptide b or y ion+glycan fragment) at both sites. Proteomics dataset was searched using Sequest in Proteome Discoverer 2.5. Fold-changes of molecules were calculated as average values from affected individuals over average values from control samples. p-values were obtained using unpaired 2-tailed Student’s t test. The p-values were adjusted (reported q- values) by Benjamini-Hochberg procedure for multiple comparisons on Perseus and publicly available MetaboAnalyst 5.0 was used to draw principal component analysis score plots. Perseus was used to draw heatmaps. Targeted LC-MS / MS analysis The targeted LC-MS / MS analysis was carried out on an Orbitrap Eclipse mass spectrometer connected to UltiMate 3000 RSLC nano (Thermo Fisher Scientific, San Jose, CA, USA). MAX-enriched serum glycopeptide samples were injected into trapping column (PepMap C18, 2 cm x 100 µm, Thermo Fisher Scientific, San Jose, CA, USA) at the flow rate of 10 µL / min. After sample loading, samples were transferred to analytical column (PepMap RSLC C182 µm, 75 µm x 50 cm, Thermo Fisher Scientific, San Jose, CA, USA) at the flow rate of 300 nL / min. The analytical gradient started at 3% mobile phase B, then mobile phase B was increased to 40% over 24 minutes, 95% over 2 minutes, and maintained at 95% for another 7 minutes. Thereafter, mobile phase B was decreased to 2%, and the analytical column was reconditioned for 7 minutes. While an electrospray voltage of 2.0 kilovolt (kV) was fixed in positive ion mode, MS spectra at a resolution of 120,000 and MS / MS spectra at a resolution of 30,000 in parallel reaction monitoring mode were obtained with stepped collision energy set at 15, 30, and 45%. Skyline was utilized to build the Attorney Docket No.07039-2225WO1 / 2023-182 inclusion list, which incorporated the targeted precursor mass to charge ratio (m / z) of glycopeptides and charge state. All targeted PRM raw files were processed in Skyline to generate extracted ion chromatogram (XIC) and perform peak area integration as described elsewhere. See, for example, MacLean et al., Bioinformatics 26, 966-968 (2010). RESULTS Demographics and clinical features of affected individuals The demographic, clinical, and biochemical information of 35 individuals affected with PMM2-CDG included in this study are shown in Table 1. Samples 3 and 15 were obtained from the same affected individual who was enrolled in a single investigational new drug protocol with epalrestat, an aldose reductase inhibitor previously shown to improve phosphomannomutase enzyme activity and glycosylation in vitro (sample 3 was collected at the age of 6 years at baseline and sample 15 was collected 6 months later on epalrestat treatment). The mean age of the 22 male and 13 female subjects was 12?years (range 1-36). Eight affected individuals were adults over 18 years of age, while the remaining 27 were children. The median total NPCRS score was 23 (moderate phenotype), ranging from 9 to 37 with 6 individuals classified as mild, 18 as moderate, and 11 as severe phenotypes. See, for example, Achouitar et al., J. Inherit. Metab. Dis.34, 923-927 (2011) and Ligezka et al., Mol. Genet. Metab.136, 145-151 (2022). All affected individuals had ataxia and global developmental delay. Four subjects were noted to have learning disabilities without intellectual disability (two with genotypes p.R123Q / p.C241S (corresponding to samples 26 and 30), p.R141H / p.C241S (sample 20) and p.Y229S / p.T237R (sample 22)) (Table 1). Notably, another individual with the genotype p.Y229S / p.T237R (sample 23) had intellectual disability. Seven affected individuals were able to walk without support (two with genotypes p.Y229S / p.T237R (samples 22 and 23), two with genotypes p.R123Q / p.C241S (samples 26 and 30), and the others with genotypes p.F119L / p.F119L (sample 10), p.R141H / p.C241S (sample 25) and p.R141H / p.Y229S (sample 36)). All affected individuals had multisystem disease including peripheral organ involvement in addition to neurologic involvement. Nine patients had clinical seizures (corresponding to samples 6, 7, 11, 13, 18, 19, 27, 28 and 35, Table 1) and one patient with genotype p.R141H / p.F119L (sample 1) had stroke like Attorney Docket No.07039-2225WO1 / 2023-182 episodes within 6 months of sample collection. Two siblings with the shared genotype p.R141H, with the non-coding variant c.640-23A>G in their second allele, (samples 27 and 28) had retinitis pigmentosa and sensorineural hearing loss. Ten individuals had no signs of neuropathy at the time of investigation (samples 5, 8, 17, 19, 22, 23, 26, 30, 32 and 36, Table 1). One affected individual with the genotype p.R141H / p.F119L (sample 11) had recurrent deep venous thrombosis of the extremities. One affected individual with the genotype p.R69C / p.D148N (sample 7) was born with a complex cardiac malformation (transposition of the great arteries), and another affected individual with the genotype p.R141H / p.F119L (sample 12) had gastrointestinal dysmotility requiring feeding through gastrostomy- jejunostomy tube. Another affected individual with the genotype p.R141H / p.V129M (sample 9) had a severe chest deformity (pectus carinatum) and another with a different genotype, R141H / p.I132T (sample 16) had severe scoliosis requiring surgery (see Table 1). Twenty-six of the thirty-five affected individuals had abnormal levels for the activity of N-glycosylated coagulation factors IX, XI, antithrombin and Protein C, and endocrine parameters (adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), insulin-like growth factor binding protein (IGFBP3)) and normal liver transaminases (see Table 1). One of the affected individuals, with the genotype p.P113L / p.T237R (corresponding to sample 24), had an unusual course of disease with early progressive liver failure. This individual developed intermittent vomiting, chronic abdominal pain, and recurrent ascites requiring diuretic therapy and repeated paracenteses. Her liver ultrasound showed cirrhosis. Due to end-stage liver disease, hepatic encephalopathy, and esophageal variceal bleeding, she underwent a deceased donor orthotopic liver transplant at the age of 4 years. Although a pretransplantation serum sample was not available, a sample after liver transplantation was obtained as she was enrolled in a CDG natural history study (sample 24).. As shown in Table 1, the most common genotype was p.R141H / p.F119L, seen in 3 affected individuals (corresponding to samples 1, 11, and 12). Overall, the most common pathogenic variant was, as expected, p.R141H (20 / 35 affected individuals), followed by p.T237R (5 / 35), p.F119L (4 / 35, one of them homozygous), p.C241S (4 / 35) and p.P113L (4 / 35). All genotypes have been previously reported as pathogenic except two: p.T118A (corresponding to sample 29) and p.Y229S (sample 36), which are reported to have Attorney Docket No.07039-2225WO1 / 2023-182 “uncertain significance” (ClinVar accessions RCV000310325 and RCV000078596.7, respectively). See, for example, Ligezka et al., Ann. Neurol.90, 887-900 (2021); Kjaergaard et al., Eur. J. Hum. Genet.7, 884-888 (1999); Vals et al., Am. J. Med. Genet. A.173, 1620- 1624 (2017); Yuste-Checa et al., Hum. Mutat.36, 851-860 (2015). No genotype-phenotype correlation was noted in the affected individuals except in cases with the genotype p.C241S, which has previously been described as “mild” due to its association with mild ataxia and variable learning difficulties. See, for example, Vals et al., Am. J. Med. Genet. A.173, 1620- 1624 (2017). Two individuals with this variant (samples 25 and 26) had comparable clinical phenotypes with normal CDT results. However, two other individuals with this variant (samples 20 and 30) had classic abnormal CDT at the adult age of 21 and 25, respectively. See, for example, Vals et al., Am. J. Med. Genet. A.173, 1620-1624 (2017). Mass spectrometry of intact transferrin for detecting CDT was performed as part of the standard of care in all 35 affected individuals as described elsewhere. See, for example, Biffi et al., Clin. Biochem.40, 1431-1434 (2007). Transferrin usually contains two biantennary sialylated N-glycans (di-oligo transferrin). PMM2-CDG patients typically lack one or both of them. The ratio of singly glycosylated transferrin (mono-oligo) to di-oligo is normally ?0.06. The ratio of non-glycosylated (a-oligo) to di-oligo transferrin is normally ?0.011. Mono-oligo to di-oligo transferrin ratios in affected individuals ranged from 0.03 (normal) to 1.93. A-oligo to di-oligo ratios ranged from 0.002 (normal) to 0.66. Five affected individuals with age in the range 6-23 years had fully normal CDT results even though they all had genetically and / or enzymatically confirmed PMM2-CDG. Two of these individuals (samples 25 and 25) had the variant p.C241S, which has been associated with “mild” disease. See, for example, Vals et al., Am. J. Med. Genet. A.173, 1620-1624 (2017). Two other individuals with normal CDT results (samples 27 and 28) had “severe” NPCRS scores, while the fifth individual (sample 24) donated their sample after liver transplantation. Glycoproteomic analysis of serum proteins Seven individuals (discovery set: samples 1 to 7, Table 1) with PMM2-CDG were chosen along with seven age- and sex-matched controls for an in-depth analysis of the serum glycoproteome to identify glycopeptide biomarkers in PMM2-CDG. CDT results by mass spectrometry-based protein-level measurements were confirmed with TMT-based relative Attorney Docket No.07039-2225WO1 / 2023-182 quantitation: peptides from transferrin with unoccupied N-glycosylation sites were increased in PMM2-CDG (Fig.1B, Fig.7A). Increased abundance of peptides with unoccupied N- glycosylation sites derived from several other serum proteins in PMM2-CDG were observed (Fig.7B). For glycoproteomics analysis, serum-derived peptides were multiplexed with tandem mass tags (TMT) for relative quantitation followed by N-glycopeptide enrichment by SEC and LC-MS / MS analysis (Fig.1B). Distribution of identified glycopeptides by class is shown in Fig.8A-8C. Alpha-1-acid glycoproteins 1 and 2 (ORM1 and ORM2) contributed the largest number of glycopeptides, 297, for any protein. The most frequently identified glycans on glycopeptides were the sialylated biantennary glycans Hex5HexNAc4NeuAc2(352 glycopeptides) and Hex5HexNAc4NeuAc1(230 glycopeptides) (Table 3). Principal component analysis (PCA) performed using TMT-based relative abundance values of glycopeptides clustered PMM2-CDG and control samples separately (Fig.1C). Table 3. List of glycopeptides identified and their relative abundance across samples from TMT reporter ion intensity. Peptide sequence (N SEQ Glycan Glycosylated Gene UniProt Average fold- ID Composition amino acid Symbol Accession change ol Attorney Docket No.07039-2225WO1 / 2023-182 Ac1 39 FSDGLESJSSTQFEV 14 Hex6HexNAc2 226 / 226 C4A P0C0L4;P0C 10.576 Attorney Docket No.07039-2225WO1 / 2023-182 Ac1 39 EEQFJSTYR 38 Hex5HexNAc3Neu 177 IGHG4 P01861 4.356 Attorney Docket No.07039-2225WO1 / 2023-182 JWSLPNR 61 Hex5HexNAc4Neu 245 PLTP P55058 3.230 Ac2Fuc1 Attorney Docket No.07039-2225WO1 / 2023-182 Ac2 39 AGLQAFFQVQECJK 85 Hex6HexNAc3Neu 358 CP P00450 2.714 Attorney Docket No.07039-2225WO1 / 2023-182 DTFVJASR 109 Hex6HexNAc3Neu 238 SERPIN P05155 2.422 Ac1Fuc1 G1 Attorney Docket No.07039-2225WO1 / 2023-182 AVJITSENLIDDVVS 132 Hex6HexNAc3Neu 415 C9 P02748 2.216 LIR Ac1 Attorney Docket No.07039-2225WO1 / 2023-182 Ac2 SVQEIQATFFYFTPJ 158 Hex6HexNAc5Neu 72 / 72 ORM1 P02763;P196 2.055 Site-specific alterations in N-glycosylation of serum proteins Glycosylation changes (q<0.05) were found in 371 unique N-glycopeptides from 85 glycoproteins (Fig.1D, 1E).136 glycopeptides from 39 proteins were elevated with an average fold-change (PMM2-CDG / controls) of ?2-fold (q<0.05).14 of these glycopeptides bore paucimannose (3 or fewer hexose residues) or chitobiose-core glycan composition. Glycopeptides from three proteins, alpha-1-acid glycoprotein 1 (ORM1, glycopeptide containing amino acid glycosylation site Asn103), alpha-1-acid glycoprotein 2 (ORM2, Asn103) and coagulation factor XII (F12, Asn249) bearing the truncated glycan, Hex1HexNAc2, were found to be elevated ?50-fold (average fold-change, PMM2- Attorney Docket No.07039-2225WO1 / 2023-182 CDG / controls) with undetectable levels in several controls. Glycopeptides bearing the tetrasaccharide, Hex2HexNAc2 from attractin (ATRN, Asn416), complement C3 (C3, Asn85), immunoglobulin heavy constant mu chain (IGHM, Asn46) and F12 (Asn249) were also high in PMM2-CDG. Glycopeptides bearing the paucimannose glycan Hex3HexNAc2 from F12 (Asn249) and galectin-3-binding protein (LGALS3BP, Asn551) were also elevated. (Fig.2A and Table 3). Oligomannose glycopeptides containing 6 or fewer mannose residues from several proteins were elevated including transferrin (Asn432: Hex4HexNAc2), ATRN (Asn416: Hex4HexNAc2), alpha-1-antitrypsin (SERPINA1, Asn271: Hex5HexNAc2), complement proteins C4 (Asn226: Hex6HexNAc2, Hex5HexNAc2and Hex4HexNAc2) and C3 (Asn85: Hex4HexNAc2) (Fig.2A, 3A). A number of hybrid glycopeptides were increased in affected individuals. The glycopeptide from transferrin (TF, Asn432) with glycan composition Hex5HexNAc3NeuAc1was elevated in PMM2-CDG. Glycopeptides from several glycoproteins with the hybrid glycan composition Hex6HexNAc3NeuAc1Fuc1, corresponding to a fucosylated hybrid glycan, were elevated: ceruloplasmin (CP, Asn138), hemopexin (HPX, Asn187), immunoglobulin heavy chain constant gamma 1 (IGHG1, Asn180) and IGHM (Asn209) (Fig.2A, 3B). The levels of hybrid glycopeptides with the glycan composition Hex6HexNAc3NeuAc1 were increased at 25 glycosylation sites derived from 19 proteins including ORM1 / ORM2 (Asn72), prothrombin (F2, Asn121) and beta-2-glycoprotein 1 (APOH, Asn253) (Fig.2A and Table 3). 87 glycopeptides derived from 24 proteins had decreased abundance (average fold- change?0.5, q<0.05) in PMM2-CDG. A majority of these were of the hybrid / complex type with high-mannose glycopeptides accounting for a small minority. Complex mono- and di- sialylated biantennary glycans accounted for 20 of these glycopeptides derived from several proteins including kallistatin (SERPINA4, Asn157), CD207 (Asn180) and N- acetylgalactosaminyltransferase 5 (GALNT5, Asn845). Complex di- and tri-sialylated triantennary glycans accounted for an additional 13 glycopeptides decreased in abundance, mainly from plasma protease C1 inhibitor (SERPING1, Asn253), clusterin (CLU, Asn86) and transferrin (Asn630) (Fig.2A and Table 3). Box plots representing altered glycopeptides between PMM2-CDG and control groups are shown in Fig.2A, and the most elevated and Attorney Docket No.07039-2225WO1 / 2023-182 decreased glycopeptides (average fold-change, PMM2-CDG / controls, q<0.05), are shown in Fig.2B, 2C. Changes in glycan microheterogeneity Patterns of change in the overall microheterogeneity were observed at some glycosylation sites in PMM2-CDG. Several oligomannose glycopeptides at Asn226of complement C4 showed changes: Man4GlcNAc2, Man5GlcNAc2and Man6GlcNAc2glycopeptides were elevated while Man8GlcNAc2 and Man9GlcNAc2 glycopeptides were reduced in PMM2-CDG. Specifically, Man5GlcNAc2 and Man6GlcNAc2 glycopeptides from C4 (Asn226) were elevated 45- and 16-fold respectively in PMM2-CDG (average fold-change PMM2-CDG / controls; q=0.0006 and 0.0004, respectively) (Fig.3A). Data from the protein- level measurements showed that complement proteins C4A and C4B (both of which share the tryptic peptide sequence that contains this glycosylation site) were not different in their abundance in PMM2-CDG at the protein level (average fold-change PMM2-CDG / controls of 1.2 and 1.1, respectively, with q=0.41 and 0.52 respectively). However, the non-glycosylated peptide containing the glycosylation site Asn226was elevated 6-fold in PMM2-CDG compared to controls (q=0.0099) (Fig.7B). This suggested that there were two changes at this site in PMM2-CDG: the first, an overall decrease in glycosylation site occupancy; and second, the glycosylation site occupied, Man5GlcNAc2 and Man6GlcNAc2 glycans were increased and Man8GlcNAc2or Man9GlcNAc2glycans were decreased. It was also observed at Asn138of ceruloplasmin where hybrid glycans with the composition Hex6HexNAc3NeuAc1Fuc1 and Hex6HexNAc3NeuAc1 and the complex monosialylated glycan Hex5HexNAc5NeuAc1Fuc1 were increased in PMM2-CDG (Fig.3B). The peptide from ceruloplasmin with non-glycosylated Asn138, however, was elevated 5-fold in PMM2-CDG (q=0.0096), while the protein level was relatively unchanged (average fold- change PMM2-CDG / controls of 1.05, q=0.69) (Fig.7B). This suggested a decrease in glycosylation at this site along with an increase in hybrid glycans where the site as glycosylated. Attorney Docket No.07039-2225WO1 / 2023-182 Hypoglycosylation of specific sites on haptoglobin As glycosylation changes in haptoglobin have previously been described in the context of PMM2-CDG (see, for example, Bruneel et al., Clin. Chim. Acta.470, 70-74 (2017) and Ferens-Sieczkowska et al., Glycoconj. J.16, 573-577 (1999)), the glycosylation patter was further studied. Haptoglobin-derived tryptic peptide NLFLN207HSEN211ATAK (SEQ ID NOs: 5, 8, 9, 12, 13, 15-17, 23, 25, 27, 28, 30, 33, 35, 37, 39, 42, 43, 44, 46, 47, 51, 53, 56, 57, 59, 60, 64, 65, 67, 69, 74, 76, 84, 90, 99, 101, 104, 108, 124, 148, 149) contains two known glycosylation sites. The fully glycosylated peptide (both sites occupied) was decreased while peptides glycosylated on a single site were increased in PMM2-CDG (Fig. 3C, 3D, 3E). These findings indicated hypoglycosylation of these sites in haptoglobin in PMM2-CDG. Streamlined glycoproteomic profiling An independent set of 17 samples from individuals with PMM2-CDG (samples 8 to 24) and 17 controls was analyzed with a streamlined method in which glycopeptides were enriched using mixed-mode anion exchange (MAX) cartridges (Fig.4A) and each sample was analyzed separately by LC-MS / MS in a single-shot run (Table 1, profiling set). Figure 4B shows a heatmap of the most prominent glycosylation changes in PMM2- CDG. The only glycopeptide that was found in all 17 samples but absent in all controls is the glycopeptide with amino acid sequence and glycan composition FSDGLESN226(Man5GlcNAc2)SSTQFEVK (SEQ ID NO: 7) derived from complement C4. Several other glycopeptides were found in many, but not all, samples from individuals with PMM2-CDG and were absent from all controls. Haptoglobin-derived glycopeptides with the peptide sequence NLFLN207HSEN211ATAK (SEQ ID NOs: 5, 8, 9, 12, 13, 15-17, 23, 25, 27, 28, 30, 33, 35, 37, 39, 42, 43, 44, 46, 47, 51, 53, 56, 57, 59, 60, 64, 65, 67, 69, 74, 76, 84, 90, 99, 101, 104, 108, 124, 148, 149), which contain two glycosylation sites but were only glycosylated at one of them, were only detected in samples from affected individuals but not in controls; for example, glycopeptides with composition Hex5HexNAc4NeuAc2 at Asn211or Hex5HexNAc4NeuAc2Fuc1 at Asn207were found in 12 and 8 affected individuals, respectively, but in none of the controls. The glycopeptide from attractin (ATRN) with Attorney Docket No.07039-2225WO1 / 2023-182 Man4GlcNAc2 at Asn416was found in samples from 11 affected individuals and with low intensity in only two controls. Many complement C4-derived glycopeptides observed to be elevated in the initial discovery set were also identified in this profiling set. Similar to TMT- based discovery data, the profiling set revealed a differential abundance of high mannose containing glycopeptides from C4 (Asn226) in individuals with PMM2-CDG. The glycopeptides from C4 (Asn226) bearing Man6GlcNAc2and fewer mannose residues were only found in individuals with PMM2-CDG; on the other hand, in control samples, only glycopeptides with the composition Man7GlcNAc2, Man8GlcNAc2 and Man9GlcNAc2 were detected at this site. Man6GlcNAc2glycopeptide was identified in 8 affected individuals but not in any of the control samples. The peak area for glycopeptides bearing Man7-9GlcNAc2was lower in all individuals affected with PMM2-CDG. A representative MS / MS spectrum from the sample of an affected individual for the Man5 glycan-bearing glycopeptide derived from C4 (Asn226) is shown in Fig.4C. By the streamlined profiling method using MAX- based enrichment, some of the paucimannose glycopeptides that were identified to be elevated in affected individuals in the TMT-based discovery experiment were not detected. This could be due to single shot LC-MS / MS runs of MAX-enriched fractions not being as comprehensive as the analysis of multiple fractions in the TMT-based discovery experiment. Another reason could be the differences in the basis of the enrichment methods. The downregulated glycopeptides common to the discovery and profiling sets also included a Man7GlcNAc2glycopeptide on Asn85site of complement C3, which was identified in 15 out of 17 affected individuals and all 17 controls. The peak area of this glycopeptide was lower in all individuals with PMM2-CDG as compared to controls. Eight other glycopeptides which were decreased in samples from individuals with PMM2-CDG were complex and hybrid glycopeptides containing site Asn241of haptoglobin, which is concordant with changes observed at this site in the TMT-based experiment. This cohort included an affected individual under a single patient IND protocol who was sampled twice. Sample 15 was collected from this individual at 6 months of treatment with the aldose reductase inhibitor epalrestat, which was being tested to improve phosphomannomutase (PMM2) enzyme activity. An archived sample from this individual at baseline (sample 3) was also analyzed using this streamlined method. The sample drawn after Attorney Docket No.07039-2225WO1 / 2023-182 treatment showed a lower peak area for the Man5GlcNAc2 bearing glycopeptide derived from C4 (Asn226) as compared to the sample at baseline (ratio of normalized peak areas, at 6 months of treatment to baseline, 0.06). Another interesting case involved sample 24, which was donated by a different individual after liver transplantation. Although a corresponding pre-transplantation sample was unavailable for this individual, the peak area for this glycopeptide was lower than in all other samples from individuals with PMM2-CDG (ratio of normalized peak areas, sample 24 to average of all other affected individuals, 0.007) (Fig. 4D). Development of a targeted mass spectrometry assay A targeted method where MAX-enriched samples were analyzed by parallel reaction monitoring (PRM) for selected candidate glycopeptides was developed. This method was suitable for analysis in a clinical setting due to lower mass spectrometry analysis time and enhanced sensitivity (Fig.5A). Four glycopeptide candidates were selected for targeted analysis based on the TMT-based discovery experiment and profiling experiments with MAX-enriched glycopeptides. The targeted glycopeptides are EN103(Hex1HexNAc2)GTISR (SEQ ID NO: 3; alpha-1-acid glycoprotein 1, ORM1), EN103(Hex1HexNAc2)GTVSR (SEQ ID NO: 4; alpha-1-acid glycoprotein 2, ORM2), N249(Hex1HexNAc2)VTAEQAR (SEQ ID NO: 6; coagulation factor XII, F12) and FSDGLESN226(Man5GlcNAc2)SSTQFEVK (SEQ ID NO: 7; complement C4). The PRM assay for the selected peptides was first tested on 8 samples from individuals with a known diagnosis of PMM2-CDG and 8 controls (Table 1, samples 21 to 28). This included a subset of samples in which profiling experiments were already carried out along with an additional four samples from individuals with PMM2-CDG who were reported to have control-like profiles based on their CDT results. The three target glycopeptides from ORM1, ORM2, and F12 bearing the paucimannose glycan Hex1HexNAc2 were not detected in any of the samples. However, the target glycopeptide FSDGLESN226(Man5GlcNAc2)SSTQFEVK (SEQ ID NO: 7) from C4 was detected in all 8 samples from affected individuals but in none of the controls. This target was detected as a doubly charged precursor ion with m / z of 1496.1216 at a retention time of 21 minutes. This glycopeptide was detected in five individuals with PMM2-CDG who had CDT results within the reference range. A representative targeted LC-MS / MS extracted chromatogram of the Attorney Docket No.07039-2225WO1 / 2023-182 target glycopeptide detected in the sample from an affected individual (sample 24) is shown in Fig.5B and an extracted chromatogram from a control sample at the same retention time is shown in Fig.5C. Levels of this target glycopeptide in samples from affected individuals and controls that were used for testing the targeted assay are shown in Fig.5D. PRM assay successfully identifies confirmed cases of PMM2-CDG as well as affected individuals with VUS Blinded analysis of 16 samples (PMM2-CDG or control) was performed using the above PRM assay. The assay was 100% accurate in assigning individuals to their respective groups based on the targeted detection of the glycopeptide FSDGLESN226(Man5GlcNAc2)SSTQFEVK (SEQ ID NO: 7) . This glycopeptide was not detected in any of the control samples. Representative LC-MS / MS extracted chromatograms for affected individuals are shown in Fig.6A, 6B, 6C, 6D and extracted chromatograms for controls at the same retention time are shown in Fig.6E, 6F, 6G, 6H. This glycopeptide was also detected in two individuals who had variants of uncertain significance (VUS) in trans with the common variant R141H in PMM2: samples 29 (p.T118A, “Uncertain significance,” ClinVar accession RCV000310325) and 36 (p.Y229S, “Uncertain significance,” ClinVar accession RCV000078596.7) (Table 1). Taken together, these results demonstrate that an elevated level of one or more particular glycopeptides in blood of a mammal (e.g., a human) can be used to identify that mammal as having PMM2-CDG. For example, an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and / or an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide in blood of a mammal (e.g., a human) can be used to identify that mammal as having PMM2-CDG. Attorney Docket No.07039-2225WO1 / 2023-182 Example 2: Glycopeptide Alterations in Other CDGs This Example describes the hypoglycosylation of a unique N-glycosylation site of albumin. Albumin is an abundant plasma polypeptide but it has long been considered a non- glycosylated polypeptide. A glycosylation site on albumin, Asn123was recently reported (Garapati et al., J. Transl. Med., 22(1):454 (2024)). In this study, three different glycopeptides from albumin showed significantly lower levels in PMM2-CDG patients compared to controls (Fig.12A). METHODS Experimental steps for MPI-CDG Separate glycoproteomics experiments were performed with serum samples from seven patients with MPI-CDG along with seven controls. These experiments were performed using methods similar to the “discovery” glycoproteomics experiment described above. Serum protein digestion Bicinchoninic acid (BCA) protein assay was used to determine protein concentration of serum samples. Equal amount of total protein from each serum sample was vacuum-dried and reconstituted in 8 molar (M) Urea in 50 mM triethylammonium bicarbonate (TEAB), pH 8.5. Proteins were reduced by incubation with dithiothreitol at a final concentration of 10 mM (Sigma) at 37 °C for 45 minutes. Samples were then cooled to room temperature and alkylated by incubation with 40 millimolar (mM) iodoacetamide (Sigma) for 15 minutes in the dark at room temperature. The samples were diluted with 50 mM TEAB to a final urea concentration of <1M and digestion was carried out with trypsin (Worthington, TPCK treated) at a ratio of 1:20 (trypsin:total protein) at 37 °C overnight. Tandem Mass Tag (TMT) labeling of peptides and glycopeptide enrichment using size- exclusion chromatography Peptides derived from serum samples of affected individuals (n=7) and controls (n=7) were labeled with tandem mass tag (TMTPro, Thermo Fisher) reagents as per the manufacturer’s instructions. Labeled peptide samples were pooled, dried and resuspended 100 microliter (?L) of 0.1% formic acid and loaded onto Superdex peptide 10 / 300 column Attorney Docket No.07039-2225WO1 / 2023-182 (GE Healthcare) for size-exclusion chromatography (SEC). Isocratic flow with 0.1% formic acid was used and 48 fractions were collected over a run time of 130 minutes. Early fractions from SEC collected over 55 minutes starting at 40 minutes after injection were selected based on the UV profile (214 nanometer (nm), 220 nm) and used for LC-MS / MS. These fractions were dried down in a speed vacuum system and re-suspended in 0.1% formic acid for LC- MS / MS analysis. LC-MS / MS analysis of SEC fractions LC-MS / MS parameters used were as described elsewhere. See, for example, Zhao et al., Cell Host Microbe 28, 586-601 e586 (2020); Saraswat et al., Mol. Omics.17, 939-947 (2021); and Budhraja et al, J. Inherit. Metab. Dis.46, 76-91 (2023). Briefly, 11 early fractions from SEC were analyzed by Orbitrap Exploris 480 mass spectrometer (Thermo Fisher Scientific) for glycoproteomics. Peptides were separated by liquid chromatography on an EASY-Spray column (75 micrometer (µm) × 50 centimeter (cm), PepMap RSCL C18, Thermo Fisher Scientific) packed with 2 ?m C18 particles, and were maintained at 50 °C. 0.1% formic acid in water (solvent A; sol A) and 0.1% formic acid in acetonitrile (solvent B; sol B) were used as solvents. Peptides were trapped on a trap column (100 millimeter (mm) × 2 cm, Acclaim PepMap100 Nano-Trap, Thermo Fisher Scientific) at a flow rate of 20 microliters per minute (µL / minute). LC separation was performed at a flow rate of 300 nanoliters per minute (nL / minute) and the following gradient was used: equilibration at 3% solvent B from 0 to 4 minutes, 3% to 10% sol B from 4 to 10 minutes, 10% to 35% sol B from 10.1 to 125 minutes, 35% to 80% sol B from 125 to 145 minutes followed by equilibration for next run at 5% sol B for 5 minutes. DDA mode was used with top 15 ions isolated at a window of 0.7 m / z and default charge state of +2. Precursors with charge states ranging from +2 to +7 were considered for MS / MS events. Normalized stepped collision energy was applied to fragment precursors at energies of 15, 25, 40%. Precursor ions were acquired in the Orbitrap mass analyzer in m / z range of 350-2,000 at a resolution of 120,000 (at m / z 200). Automatic gain control for MS and MS / MS were 106and 105and injection time to reach AGC were 50 ms and 250 ms respectively. Exclude isotopes feature was set to “on” and 60 second dynamic exclusion was applied. Data acquisition was performed with option of “lock mass” (m / z 441.12002) for all data. Attorney Docket No.07039-2225WO1 / 2023-182 Database searching, data analysis and statistics Database searching was performed using pGlyco. See, for example, Zeng et al., Nat Methods 18, 1515-1523 (2021) and Liu et al., Nat Commun 8, 438 (2017). Glycan databases already available with the software were used and Uniprot Human Reviewed protein sequences were used as proteins sequence FASTA file. Fully tryptic cleavage specificity with 2 missed cleavages was used and precursor and fragment tolerance were set to 10 and 20 parts per million (ppm) respectively. Carbamidomethylation of cysteine was set as fixed modification and oxidation of methionine as a variable modification. For TMT-based experiments, TMTPro at lysine was set as a fixed modification and TMTPro at peptide N- terminal was set as variable modification. The results were filtered to retain entries which had 1% false discovery rate (FDR) at the glycopeptide level. Reporter ion quantitation was performed on Proteome Discoverer (reporter ion quantifier node) and IDs were matched with quantitation on a scan-to-scan (MS / MS) basis. Peptide-spectrum matches (PSMs) for glycopeptides were combined to reflect unique glycopeptides per search by glycan composition and peptide sequence and summed-up reporter ion intensities were calculated. Spectra were manually verified for several glycan oxonium ions and quality. All sialic acid glycopeptides’ spectra were verified for presence of sialic acid-specific oxonium ions at m / z 274.09, 292.10 and / or 657.23. Experimental steps for SRD5A3-CDG Separate glycoproteomics experiments were performed with serum samples from seven patients with SRD5A3-CDG along with seven controls. These experiments were performed using methods similar to the methods used for the MPI-CDG glycoproteomics experiment described above. Experimental steps for MAN1B1-CDG Separate glycoproteomics experiments were performed with serum samples from seven patients with MAN1B1-CDG along with seven controls. These experiments were performed using methods similar to the methods used for the MPI-CDG glycoproteomics experiment described above. Attorney Docket No.07039-2225WO1 / 2023-182 RESULTS A glycopeptide signature of MPI-CDG Seven individuals with MPI-CDG were chosen along with seven age- and sex- matched controls for an in-depth analysis of the serum glycoproteome to identify glycopeptide signatures in MPI-CDG. Serum-derived peptides were multiplexed with tandem mass tags (TMT) for relative quantitation followed by N-glycopeptide enrichment by SEC and LC-MS / MS analysis. A total of 1698 glycopeptides were identified. An overview of glycopeptide changes in MPI-CDG patient samples relative to controls is shown in Fig.9A. Three glycopeptides with the glycan composition Hex1HexNAc2from three different proteins (C4, ORM1 and F12) were significantly elevated. Several glycopeptides from FGG and IGHM with complex sialylated glycans were significantly decreased. Significant changes in the microheterogeneity at glycosylation site Asn226of C4 was also observed, with the levels of the Man5GlcNAc2-bearing glycopeptide at this site showing a significant increase in MPI- CDG patients (Fig.9B). A glycopeptide signature of SRD5A3-CDG Seven individuals with SRD5A3-CDG were chosen along with seven age- and sex- matched controls for an in-depth analysis of the serum glycoproteome to identify glycopeptide signatures in SRD5A3-CDG. Serum-derived peptides were multiplexed with tandem mass tags (TMT) for relative quantitation followed by N-glycopeptide enrichment by SEC and LC-MS / MS analysis. A total of 2200 glycopeptides were identified. An overview of glycopeptide changes in SRD5A3-CDG patient samples relative to controls is shown in Fig. 10A. Among the significantly increased glycopeptides were singly glycosylated glycopeptides from HP which had two N-glycosylation sites, where one of the N- glycosylation sites remained unoccupied. In addition, C4-derived glycopeptide with the Man5GlcNAc2-glycan at Asn226was also significantly increased (Fig 10A). A few additional significantly changing glycopeptides are shown in Fig 10B. Further, albumin-derived glycopeptides with glycosylation at the novel site Asn123were also detected with significant alterations in SRD5A3-CDG patient samples (Fig.12B). Attorney Docket No.07039-2225WO1 / 2023-182 A glycopeptide signature of MAN1B1-CDG Seven individuals with MAN1B1-CDG were chosen along with seven age- and sex- matched controls for an in-depth analysis of the serum glycoproteome to identify glycopeptide signatures in MAN1B1-CDG. Serum-derived peptides were multiplexed with tandem mass tags (TMT) for relative quantitation followed by N-glycopeptide enrichment by SEC and LC-MS / MS analysis. A total of 2408 glycopeptides were identified. An overview of glycopeptide changes in MAN1B1-CDG patient samples relative to controls is shown in Fig. 11A. Among the significantly increased glycopeptides were several glycopeptides from different glycoproteins bearing hybrid type N-glycans. Sialylated complex N-glycans from several proteins showed significant decrease. Fig 11B shows data from patient and control samples with relative quantitation of hybrid glycopeptides from glycoproteins including APOD, APOB and IGHG1. Further, a hybrid glycopeptide from albumin with the glycan Hex6HexNAc3NeuAc1at Asn123was detected in all patient samples but in none of the control samples (Fig.12C). Example 3: Abbreviations of Exemplary Glycans. This Example provides both abbreviations for exemplary carbohydrates (e.g., (monosaccharides) that can be present in glycans attached to glycopeptides described herein and abbreviations for exemplary glycans that can be attached to glycopeptides described herein. Exemplary carbohydrate abbreviations hex = hexose man = mannose glc = glucose gal = galactose fuc = fucose HexNAc = N-acetylhexoseamine GlcNAc = N-acetylglucosamine NeuAc = N-acetylneuraminic acid Attorney Docket No.07039-2225WO1 / 2023-182 Exemplary glycan abbreviations Hex5HexNAc = 5 hexose moieties and 1 N-acetylhexoseamine moiety Hex5HexNAc2= 5 hexose moieties and 2 N-acetylhexoseamine moieties Hex1HexNAc2 = 1 hexose moiety and 2 N-acetylhexoseamine moieties Hex5HexNAc4NeuAc2Fuc1 = 5 hexose moieties, 4 N-acetylhexoseamine moieties, 2 N-acetylneuraminic acid moiety, and 1 fucose moiety Hex5HexNAc4NeuAc2= 5 hexose moieties, 4 N-acetylhexoseamine moieties, and 2 N-acetylneuraminic acid moieties Hex5HexNAc4NeuAc1= 5 hexose moieties, 4 N-acetylhexoseamine moieties, and 1 N-acetylneuraminic acid moiety; and Hex3HexNAc2= 3 hexose moieties and 2 N- acetylhexoseamine moieties Man5GlcNAc = 5 mannose moieties and 1 N-acetylglucoseamine moiety Man5GlcNAc2= 5 mannose moieties and 2 N-acetylglucoseamine moieties Man1GlcNAc2 = 1 mannose moiety and 2 N-acetylglucoseamine moieties Man5GlcNAc4NeuAc2Fuc1 = 5 mannose moieties, 4 N-acetylglucoseamine moieties, 2 N-acetylneuraminic acid moiety, and 1 fucose moiety Hex5HexNAc4NeuAc2 = 5 hexose moieties, 4 N-acetylhexoseamine moieties, and 2 N-acetylneuraminic acid moieties Hex5HexNAc4NeuAc1= 5 hexose moieties, 4 N-acetylhexoseamine moieties, and 1 N-acetylneuraminic acid moiety; and Hex3HexNAc2= 3 hexose moieties and 2 N- acetylhexoseamine moieties Example 4: Exemplary Sequences Exemplary PMM2 polypeptide MAAPGPALCLFDVDGTLTAPRQKITKEMDDFLQKLRQKIKIGVVGGSDFEKVQEQLGNDVVE KYDYVFPENGLVAYKDGKLLCRQNIQSHLGEALIQDLINYCLSYIAKIKLPKKRGTFIEFRN GMLNVSPIGRSCSQEERIEFYELDKKENIRQKFVADLRKEFAGKGLTFSIGGQISFDVFPDG WDKRYCLRHVENDGYKTIYFFGDKTMPGGNDHEIFTDPRTMGYSVTAPEDTRRICELLFS (SEQ ID NO:1) Attorney Docket No.07039-2225WO1 / 2023-182 Nucleic acid encoding an exemplary PMM2 polypeptide CTCGTGCCAACGTGTCTTGTAAGGTGCGGCTAGAAACTGGGGACATGGCAGCGCCTGGCCCA GCGCTCTGCCTCTTCGACGTGGATGGGACCCTCACCGCCCCGCGGCAGAAAATTACCAAAGA AATGGATGACTTCCTACAAAAATTGAGGCAGAAGATCAAAATCGGAGTGGTAGGCGGATCGG ACTTTGAGAAAGTGCAGGAGCAACTGGGAAATGATGTGGTTGAAAAATACGATTATGTGTTT CCAGAAAATGGCTTGGTAGCATACAAAGATGGGAAACTCTTGTGTAGACAGAATATTCAAAG TCATCTGGGTGAGGCCCTAATCCAAGATTTAATCAACTACTGTCTGAGCTACATTGCGAAAA TTAAACTCCCGAAGAAGAGGGGTACTTTCATTGAATTCCGAAATGGGATGTTAAACGTGTCC CCTATTGGAAGAAGCTGCAGCCAAGAAGAACGCATTGAGTTCTACGAACTCGATAAAAAAGA AAATATAAGACAAAAGTTTGTAGCAGATCTACGGAAAGAGTTTGCTGGAAAAGGCCTCACGT TTTCCATAGGAGGCCAGATCAGCTTTGATGTCTTTCCTGATGGATGGGACAAGAGATACTGT CTGCGACATGTGGAAAATGACGGTTATAAGACCATTTATTTCTTTGGAGACAAAACTATGCC AGGTGGCAATGACCATGAGATCTTCACAGACCCCAGAACCATGGGCTACTCCGTGACAGCGC CTGAGGACACGCGCAGGATCTGTGAACTGCTGTTCTCCTAACGTGGGAGCGGGAGGGGCGGG GTCCCGGCTGACAAGCCAGCATAGGGCATTCGGTGGCCAGAGCCGAGGGTCCTCCCACACGT GCTCACCCACCCGCAGCCTAGGCAGGCTCTGCATGCTATGCCAGGCATGTGCAGTCTGGACT TCCACCTCCAGTGCCAGAAACTTCCAGAAGGAAGGAGAAAACTCTTGTCAAGAATGGCCCAG AGGAATGCCTCGCACAAAAGGTCTTCCCCACCCACCCCCAGCCCCCTAGTCTAATACCCACC CTGATACGTGCAATCATGTAGTTTTGGCGGAAATTTCCCCATCATTCTAGGATGATACAGAA AGAAAAACTGTGCCTGGACCCTCCCTCTTGGTGGGTCTGTGGAAACATAAGCGGTTTTTTTA ATGGGCCCCTGCATCAATACCAAACATGGGGGTTTGGTAATGAGAAACCAGGACAGGCCATC TGCAGTGACCCAGCCCAGGACGAAGTTTACAAACACCTCCTGGAACGAAGCTCCCGCCTGCA TGTCACCTTGATGGGGGCTGTGAGTGGGGCAGTGTGATACCCAGTGACTAGACGCACTCTGC GTTTTCCCGTGTTTGGGGCTGAGGCCTGCTGGACAGATGGCTGGCCAAGTGGGAGCAGACCC TAGGGAGTTTGCACCTCGGCTGGGCCGGATTCGGACCGGCTCTGTGTTCACTACACTCAGAA TAGCCTGGCTGCTTCTCTGTCTCCGAGACCGGAGGTAGTGGGAACCAACAGCTGGGCTGGAG AGTTGGTGCTGGCAAAACAGTCCTTGCCCTGGGGCCGGTTCTTACCCAGGTCCAGAGAAACC AACGCGGGATGTCAGACTTCACCAAAAGGACTTTCTGGTTGCCCCTGGCTGGCTTCCTGGAG GCGTTCGCCTCTAGTTTCTCAGGGATGGAGCGAGAGCCCAGCCAGAGAACAGTAAGAGGAGC TGCTCTCCTATCTGCACTCACCCAGGCCTTCACCCAGACTTTACCACGGAGGCGGCTGAGTG CAGCTACAGCTAGGTCCGCGTCCCTCACTCTTTTCATCTTCTGCACGTTCTTCGTGAAACTG GAAGGATCCCGGGTCTCAGCTAGAACACGGTGGAAGAGAACTTTCCTAGGAAACGGTTCATG TGTCACTTTTCAGGATGTGGAAACACTGAGCCATACACCCTCCATTGCTTGGTGCTGGGGTT GTGTGGCCTCCACTGGGCACTTGCCGACCTGAGTCTGGGGCCAGGGGAGCCCAGGCTGCCCT GCACTCCTGCCTCCCAGCCCACAGCCAGGTGCTTTCATCACAGCTAAACCTGGTTCCCTCCA AACCTCCCAGCCACTCGGGCTTGTAACTGTCTGAGCCCCGGATCCGGTGGGGTGAAAGCAGC CAGCTCATCCCAGTGACTCACAGGACACAGCCATCCAGCGGCATCTTTCCTTGTCGAATGAT ACTGTAATGACCTTCCAAAGTGAAGAGTAGCACATTAAAGTGATTTTATTGTT (SEQ ID NO: 2) Attorney Docket No.07039-2225WO1 / 2023-182 Exemplary MPI polypeptide MAAPRVFPLSCAVQQYAWGKMGSNSEVARLLASSDPLAQIAEDKPYAELWMGTHPRGDAKIL DNRISQKTLSQWIAENQDSLGSKVKDTFNGNLPFLFKVLSVETPLSIQAHPNKELAEKLHLQ APQHYPDANHKPEMAIALTPFQGLCGFRPVEEIVTFLKKVPEFQFLIGDEAATHLKQTMSHD SQAVASSLQSCFSHLMKSEKKVVVEQLNLLVKRISQQAAAGNNMEDIFGELLLQLHQQYPGD IGCFAIYFLNLLTLKPGEAMFLEANVPHAYLKGDCVECMACSDNTVRAGLTPKFIDVPTLCE MLSYTPSSSKDRLFLPTRSQEDPYLSIYDPPVPDFTIMKTEVPGSVTEYKVLALDSASILLM VQGTVIASTPTTQTPIPLQRGGVLFIGANESVSLKLTEPKDLLIFRACCLL (SEQ ID NO:173) Nucleic acid encoding an exemplary MPI polypeptide ATACGTGCTTAATCCTGGTGCAGGGGGCGAGCATGGCCGCTCCGCGAGTATTCCCACTTTCC TGTGCGGTGCAGCAGTATGCCTGGGGGAAGATGGGTTCCAACAGCGAAGTGGCGCGGCTGTT GGCCAGCAGTGATCCACTGGCCCAGATCGCAGAGGACAAGCCTTATGCAGAGTTGTGGATGG GGACTCACCCCCGAGGGGATGCCAAGATCCTTGACAACCGCATCTCACAGAAGACCCTAAGC CAGTGGATTGCTGAGAACCAGGACAGCTTGGGCTCAAAGGTCAAGGACACCTTTAATGGCAA CCTGCCCTTCCTCTTCAAAGTGCTCTCAGTTGAAACACCCCTGTCCATCCAGGCACACCCTA ACAAGGAGCTGGCAGAGAAGCTGCACCTCCAGGCTCCGCAGCACTACCCCGATGCCAACCAC AAGCCAGAGATGGCCATTGCCCTCACCCCCTTCCAGGGCTTGTGTGGCTTCCGGCCAGTTGA GGAGATTGTAACCTTTCTAAAGAAGGTGCCTGAGTTTCAGTTCCTGATTGGAGATGAGGCAG CAACACACCTGAAGCAGACCATGAGCCATGACTCCCAGGCTGTGGCCTCCTCTCTGCAGAGC TGTTTCTCCCACCTGATGAAGAGTGAGAAGAAGGTGGTGGTGGAACAGCTCAACCTGTTGGT GAAGCGGATCTCCCAGCAAGCGGCTGCCGGAAACAACATGGAGGACATCTTTGGGGAGCTTT TGCTACAGCTGCACCAGCAGTACCCAGGTGATATCGGCTGCTTTGCCATCTACTTCCTGAAC CTGCTTACCCTGAAGCCTGGGGAGGCCATGTTTCTGGAGGCCAACGTACCCCATGCCTACCT GAAAGGAGACTGCGTGGAGTGCATGGCGTGTTCAGACAACACAGTTCGTGCTGGCCTGACAC CCAAGTTCATTGATGTGCCAACCCTGTGTGAAATGCTCAGCTATACCCCTAGCTCCAGCAAG GACAGGCTCTTTCTCCCAACACGGAGTCAGGAAGACCCCTACCTCTCAATCTATGACCCCCC TGTACCAGACTTCACCATTATGAAGACGGAGGTCCCTGGCTCTGTCACTGAATACAAGGTCT TGGCACTGGACTCTGCCAGCATCCTCCTGATGGTACAGGGGACAGTAATAGCCAGCACACCC ACAACCCAGACACCAATCCCTCTGCAACGTGGTGGCGTGCTCTTCATTGGGGCCAATGAGAG TGTCTCACTGAAGCTTACTGAGCCGAAGGACCTGCTGATATTCCGTGCCTGCTGTCTGCTGT AAAGGCTGCAGCCTCCCCAGCTCTCCTCTGCCAGCCACCCTAAATTCCAGCCAACCTCACCT CCTCGGGCCCAGCTCAAGCCCCCTTCCTTGCTCTGGACCCCTTAGGTATACCCTGGAAGAGC TGGGGTGGGGGAGGAGGGAGCGTGAAGGTAGTGACTCCTGAACACACCCAGGTGGAACCATC TTTGGGGAGGAGAGGCCCGTGTGAGGGGTCTGATACTCCCTTTGTCTTCCCTCTCTACTCCT CGCTACACCTGAGCCAGGCTCTTGCCAACTCTGTTCCAGCCTATGGCTTTAGGCTAGCTGTT AAATATGTGACCCAGCATTAGCTCAGCATCTGTCAGAGCAAGAGACCAGGTAATTTCTAAGA ACAGGGTTCTAGCGATGGGACTGCCCATTTCCTCAGCTGCAGAGGAGGAAAGGGAAAGGGTA GGCCTGTAGACTAACGCTGTTTACACCCTTGTTCTGTCAAAGCAATTAAAGATCACTTGTGT Attorney Docket No.07039-2225WO1 / 2023-182 TGAGGCTGTGGGGTAATGAGCACTCAGCCTTTGGGGTACCTGTTCCTAAAGTGGGCCAAAAG AGCCCTCCCTACATGATGCCCCAGTTTTTGCTTTATTCCTATTTCATACAGCTTCTCGGGGG AGTGAGCAGGCTACACTCCAGAACACCGGTATGGGAAGGAGTGGGAGAGGAAGCCAGCTTTG GCCTCACAGGCACAGCTTGCAAGCAGGCCTTGGGTCTGCCCAGAGGCACAGCTTGCAAGCAG CCCTACAGAGAAGGTGACTCAAAGGATACACCAGTCACCAGTGCAAGACTCTTCGCTCCTGT TTTTCTCTTTTTTTTTTTTTTGAGACGGAGTCTCGGTCTGTAGCCCAGGCTGGAGTGCAGTG GCACGATCTCGGCTCATTGCAAGCTCCGCCTCCCGGGTTCACGCCACTCTTCTGCCTCAGCC TCCCAAGTAGCTGGGACCACAGGCGCCCACCACCACGCCCAGCCAATTTTTTTGGTATTTTT AGTAGAGATGGGGTTTCACTGTGTTAGCCAGGATGGTCTCGATCTTCTGACCTCGTGATCCG CCCACCTCAGCCTCCCAAAGTGCTGGGATTACAGGCGTGAGCCACCACGCCTGGCCCGGCTC CTGTTTTTCAACTGGCCCTAGAGGAGGGGTCCGCAAACCAGGCTGGCAGGCCAGTTCTGGCC ATACCTGTTCATTTCCATACTGTCTGGCTGCTTTCAAGCCACAGTGGCAAAGTTGAAGAGTT GCACTAGACTGTACGGCCTGCAAAACTGAAACCATTGACTGTCAACCACTTCTCTACAACAT ACTCAACTGTTGCAGATTACAGGGACTCAGGAACCGAATTAGACAATTTTCATGGCGAGGAG AAGCCCAGTTAGCTTTCCTAAACGGGCAGGAAGTGTGAAGGAGGGAATCTCCTGATGCCCTG CTCCAGGGGTGGCACACACCTGCAAGAGGCTGTCGGCTGTCTGCTGCTGCTGAGGTTTCTGA CCTGCAATCGTAGATCCTGTCACCACAGACTAATCACTTAGTCCACTGGCTCCTTCCTGTGG GATAAAGGTTTAAATTCATGCAAAAGAATCTTTCTGGGCTTCTGCCCACACTAGAGTCCCTA TACAATGGAGTTCCAGGAAACCACCTTCAAAAATCTCCTGGGTTTTCTTGCCTCCAAATTTT CTTCAGCTAAAAAACAATAAAGATGAGCTGGAAAGAAAAGGTCTGCTAAAGGGAACCCATTC TACAGAAGTGACTTGCAAGAGCCTATTTCACTCATGCCGTCCAGTGAAACAGGCCCGAAAGT GATGCCCAGTGGGAACAGCAGAAAGGGGAGGGAGTTTCCAGAAGGAATTGCTGTAGTCAGCT GTTAAGCTATTTCTTCATTTCAGGATATCCAGGATATTCTTAACTTTTATTTTTTTGAGACG GAGTCTCGCACTGTCTCCCGGGCTGGAGTGCAGTGGCGCGATAGCTCACTGCAACCTCCGCC CACTGGGTTCAAGCGATTCTTCTGCCTCAGCTCCTGAGTAGCTGGGACTACAGGCGCCTGCC ACCACACCCAGCTAAGTTTTTGTATTTTTAGTAGAGACGGGGTTTCAGTAGAGACGGGGTGA CAGGATCTACAATTCCAGGTAAGGTCAGGTTGGTCTCAAACTCCTGACCTTGTGATTTGCTT GCCTCAGCCTCTGAAAGTGCTGGGATTACAAGCATGAGCCATTGTGCCTGGCCAAGGCCTTT AAAATCCACTGCAACACAGACACAGCTCAACTAGTGTGATTGCATTTATTCTTATAAATGTA CAGAGCTGTAGAAGTGCAAGCCAAGAGTTCTATAGAGTAGTACATAAACACCATATGGTACC ACTCCTGCTGGGAGGTAAGCCTGGATACACCCCTCTCCTCAGGAAACTGTCACCTGCAGAAC ACACAGCACTCAGAATTAAGGCAGTTTGGCCCTGGGCACATTGGTGGTATTTTGGTATGTGG CCACTGGCCCTAAACAACTGACCATTTCTACCCTGCCTCACTGCACTGTCCCACCAGGTCCC TCCAGCTTTTTCTACAAGGTAACACCCTCCTACATGGGGTCAGCCAGCTCAGAAACCTCTTC TTCAGGGACAGTTGCAGCTGAATATGCCAGAGCTGATTATTACAACAACGATGCAGAGGGCC TTGGTTTTGGGGTCCTGCCACCCTCACCCCTAGAAGCTGCTAAACACCCAGGCCATTCTGCC CTGACCACCTCCCCAACAGAGATGTAGGTCTATACTTACCTTCCACAGCCACCTCCCAGCAC ACACTGGGTCCCTCTACCTGTGTTGCTGTCTTTCTTTACACTGTGCTACATTTGATCCCTTT CCACATGTGCACTTCACCTCTGCAGACACAAGAAAGGCCTGGACATGGTCTCTGCAGATGGG GAAGGGGTTCTGGATGGAGATGTTCTTGAGCTCTACAAGCATTTGCACAAAGTGCTCAGAAT GTTGGCCACTGCATAGAGCTGCAGAGTCCCATTCCAGAACAGAGTAACCATCTGCCTCTCTT Attorney Docket No.07039-2225WO1 / 2023-182 CCCAAGACCCCAAGCTGGCATGACTCTGGTCTCTGTCCTATCTCTCTGCTGTGATGCTCCTA GCTAGTAGAGTAAGTCAGCCCCCAGATACTGTATATTCCTCTCAACCTTCCATGGTTTGAGA AAAACACAAAGATAGATGTCCATCAGGCACTCACAGGATTACCATCGTAAGGATGGTTGTCA GACAAATAACAAATAAGGCCGTATCTTTTTATTAGACTTGCTCATCTTCTAGTCACCCCTTG TGGTAGAGCGAAAAGAGTGTGTTGTCCCTCTCATGCCTCTGGTGGTCACAGGACACTGAGTA AAGCAAGAGACTGGATACTTTCCCATGTAGAACCTATACCCCAATCCCGACTATTGGGCTGG GAACCCTGTCTATGCCCATTCAAAGCTCACCATGTGGGAGGACTGCTTGGGCCTGGGAGGTT GAGGCTGCAGTGAGCTGTGATTACACCACTGCACTCCAGCCTGGGTGACAGAGACCCTGTCT CCAACAAAACAAAGCAGAACGCTCACCATGGTTCTGAGTTAAGCCAAAAAACAAAACAAAAC CTGTTGGAAAAATTCTAGAAAGAGGCTTGGTATAGAGTATAGCAAGATATACTCTCCAATTT GTGGGTAGGGGGTGTCACAGCAGAAATTATGCCTATTTCTGCTGTTTGGGCTGGGGGCTGAA AGAGGCTGTGTCACACCCAGAGGTCTGCTTAAAGCCCAATCCTGAGTATCCAGTAAGGCCCA TGCTGTGACCAGAAGAATCTGGCAATAGAATGGTCCATGCTGGAGTGAAGGGAGGCCCTCTA CACTGGTGGACTGATTTCCTCAGGCAAGGGTCTAGGAGCTGGCTTAGGTCTCTCTTACCCTT CCTGTCTGTAAGCCTCAGTCTAGGACAAAGCCCACACAGCTGTATACCCACTCTCACGAGTC CATTGCTACTTCTCAAAAGTTTAAAAAGTAAACAATAGGAAGGCACCGGACTGCTCCCTGTA GCTCCCTCTGCTGGTAATAATAAAAACTGCAGGCTTCTGGGGCCAGCCCCAGTACCTTCGAC CTAATCTTTAGCTCAAAGACTGGGTGAAGAAACTCACCCAGACCAAGGAAATACAAATAAAT AAATATGAACATGTCAGAGCAGTTTTTCTCTAACTAGGGAAGGGCAAACCAGAATCACTAAA CTCACCCGGACGGTTGGACCAGTTGGGGATGCCCCAGGTCCAGGGATTCTGGAAGCCAGGAT CCTGCTGTATCATTAAGCAACCTGCTATGATCCCTGTCATAGTTAGACAGGTGCAACCTGAA GAGGGACAAAAGGACTCACTTTATGCTGTCTTGAAGGTCAAGCCTGCAAACCATCTTAGAGC TAGGAAGAATAGAGCAAACGGAATTTCTCGAACTGGTCTCAAACAGTTTCTTTTTTGGATTG CCAGCTATAATAAACCATAAAGTGCTA (SEQ ID NO174) Exemplary SRD5A3 polypeptide MAPWAEAEHSALNPLRAVWLTLTAAFLLTLLLQLLPPGLLPGCAIFQDLIRYGKTKCGEPSR PAACRAFDVPKRYFSHFYIISVLWNGFLLWCLTQSLFLGAPFPSWLHGLLRILGAAQFQGGE LALSAFLVLVFLWLHSLRRLFECLYVSVFSNVMIHVVQYCFGLVYYVLVGLTVLSQVPMDGR NAYITGKNLLMQARWFHILGMMMFIWSSAHQYKCHVILGNLRKNKAGVVIHCNHRIPFGDWF EYVSSPNYLAELMIYVSMAVTFGFHNLTWWLVVTNVFFNQALSAFLSHQFYKSKFVSYPKHR KAFLPFLF (SEQ ID NO:175) Nucleic acid encoding an exemplary SRD5A3 polypeptide AGGCTGAGACCGGTGCGCCGCGCGCTAGTGGCCGCTCTTCCGCGGGCTAGCGGGCGGTGGGG GCGCCAGCAGCGCGGAAGGCGGGCACGCGGGCCATGGCTCCCTGGGCGGAGGCCGAGCACTC GGCGCTGAACCCGCTGCGCGCGGTGTGGCTCACGCTGACCGCCGCCTTCCTGCTGACCCTAC Attorney Docket No.07039-2225WO1 / 2023-182 TGCTGCAGCTCCTGCCGCCCGGCCTGCTCCCGGGCTGCGCGATCTTCCAGGACCTGATCCGC TATGGGAAAACCAAGTGTGGGGAGCCGTCGCGCCCCGCCGCCTGCCGAGCCTTTGATGTCCC CAAGAGATATTTTTCCCACTTTTATATCATCTCAGTGCTGTGGAATGGCTTCCTGCTTTGGT GCCTTACTCAATCTCTGTTCCTGGGAGCACCTTTTCCAAGCTGGCTTCATGGTTTGCTCAGA ATTCTCGGGGCGGCACAGTTCCAGGGAGGGGAGCTGGCACTGTCTGCATTCTTAGTGCTAGT ATTTCTGTGGCTGCACAGCTTACGAAGACTCTTCGAGTGCCTCTACGTCAGTGTCTTCTCCA ATGTCATGATTCACGTCGTGCAGTACTGTTTTGGACTTGTCTATTATGTCCTTGTTGGCCTA ACTGTGCTGAGCCAAGTGCCAATGGATGGCAGGAATGCCTACATAACAGGGAAAAATCTATT GATGCAAGCACGGTGGTTCCATATTCTTGGGATGATGATGTTCATCTGGTCATCTGCCCATC AGTATAAGTGCCATGTTATTCTCGGCAATCTCAGGAAAAATAAAGCAGGAGTGGTCATTCAC TGTAACCACAGGATCCCATTTGGAGACTGGTTTGAATATGTTTCTTCCCCTAACTACTTAGC AGAGCTGATGATCTACGTTTCCATGGCCGTCACCTTTGGGTTCCACAACTTAACTTGGTGGC TAGTGGTGACAAATGTCTTCTTTAATCAGGCCCTGTCTGCCTTTCTCAGCCACCAATTCTAC AAAAGCAAATTTGTCTCTTACCCGAAGCATAGGAAAGCTTTCCTACCATTTTTGTTTTAAGT TAACCTCAGTCATGAAGAATGCAAACCAGGTGATGGTTTCAATGCCTAAGGACAGTGAAGTC TGGAGCCCAAAGTACAGTTTCAGCAAAGCTGTTTGAAACTCTCCATTCCATTTCTATACCCC ACAAGTTTTCACTGAATGAGCATGGCAGTGCCACTCAAGAAAATGAATCTCCAAAGTATCTT CAAAGAATAAATACTAATGGCAGATCTGCGATTTCTGGGTCCACTTTCTGAGATGCTTTCTA AAACCAACCAACTGATAAAAAGTAGATGAGACTTCTCCAAGCTGCTTCACAAGCAAACTAAC CGAAAAACCGAAAATATACAAACAGCTTCACACACACACACACACACACACACACACACACA CACACACAAAGGAAGATCATCAATGGCTGCGGTAGCCTAGTAGGAATGGACTATATAATAAT ATAGCAGGTGCTCAATAACTGTTTGTTGCATTTCAGTAAAAGCAGAATAACCTTTCAAAATA ATAACAGGCTGGGTGCAATGGCTCACACCTGTTAATCCCAGCACTTCGGGAGGCCAAGGTGG GCAGTTCGCTTGGGCCCAAGAGTTCGAGACCAGCCTGGGCAACATGGTGAAACCCTATCTCC GTGAAAAAATATGAAAATTAGCCAAGAGTGGTGGCACATGCCTGTAGTCCCAGATACTTGGG AGTGGGCTGAGATGGGAGAATCGCTTGAGCCCAGGAGGTCAAGGGTACAGTGAGCCGAGGTC ATGCCACTGCACTCCAGCCTGGCCTGGGCAACAGAGCAAGACCCTGTCTCAAAATAATAATA ATATATAATTTTACACCAAAAGTTTCAGGAAAAAACGAGTTTGTTGGAGTTAGTTTATACTT TCACATATCACCACAAAGATCTCCAGTTAAATAACTATCAATATCCATTTCCATTCATCTCC CCCTCAAATCATAGCCTAACAGAACACTTTGAAAGCTCTTTTATTTAATATTTTTTTACATC CTTTGAAGGGAGTGCTTCAAAAATGAAAGCATCAGAAGATAAAATATTTTTATATTTATGCA TAGCAAGCCTTCGTGAACGGAAGTGACACACTCTGGATTGAATAATACTGTAGCCTCATTCA TATGTAGTTATTCAAATTGGATTAATGTCTGTGTGAGTTTATTTGAACTAGCAGAAAGTATC TGAAGATATTCAGGAATAAAGTTTATACTTAAAATAGCTTATGTTAAAGAAAATACCTGTGA TTAATTCAGAGGGAAATAAATGCATGGTATAAAAGAAAACCAAAAACTTAAAAAATAATACT ATAGCCTGAGCAACACATTAAAACTGCACACTTGTGCAGCGTAAGATTCTCTGGCTTATTGG CTGAGGTGTTAAGTTTATTCCTTTTATGAAGATGTCCTATTACAGTCAGCTAAGCACTAAAG CTTTGCATTTATATGTACTTTGCTATGGGGGAAAGAACCTTATGATTAATAAGACACATATC AAATGCATAGTCAATCATTCCCACCCCCATCCCTGGAGCTGTAACCCAAAACTGTTAAACTA AGATTCCTTTGTTTTTTTTGTTTTTTTGAGATGGAGTCTCACTCTGTCGCCCAGACTGGAGT GCAGTGGTGGGATCCTGGCTCACTGCAACCTCCGCCTTCTGGGTTCCAGCGATTCTCCTCTG Attorney Docket No.07039-2225WO1 / 2023-182 CCTCAGCCTCCCAAGTAGCTGGGATTACAGGCACATGCCACCATGCCCAGGTAATTGTTGTA TTTTTAGTAGAGATAGAGTTTCACCATGTTGGCCAGGCTGGTCTCAAACTCCTGACCTCAGG TGATCCACCTGCTTCGGCCTCCCAAAGTGCTGGGATTACAGGTGTAAGTCACTGCTCCCGGA TGCATGTCAAGCACATTGGAAAGTTCTTACAACAATTCTGATGGAGGATTTTCTCTCCCATC AACCAAACACCACTTAAGATTAACCTGTGGCTCAGTCTACTTAAATAAATGCCATATTTATT TTACTTATCATTTAGAATTTGCCATTCTCAGGAACAAAACTTTTTGTACATTGGAAATGGAA AACATTGCAGTTTGGTCTTAATTTCCACATGAATATCAAGTGTAATTTTTAATAAATTATTT GGAGAAAAATGTATTTTATTTTAGCATGCAATTTTATGCCCAGGTTAGACTAGAGATTTGGC TGATGTTCTGGAATCTCATTGTACTCTTAAGTAAAATAACGAGCATCCCATGACGCACCCTG TCAGGGGTTGTGAGAAAGCTGCAGTGTCCAGTTTCCCACCCCTGTTTCCTGCTGTCTCTCTC CCACTCATCCCTGTTTCTTACTCATCCCTTTTCCTTCTTTGCCCAAACATCATATTTCTAGG CAAAGATAAGAGAGGAGATAGTGATGTCCTGAAAGGGGTTCAGAACAACGTAGCATGGCCTT TGGTGAAAGCGTCACCGATGGGAAATAATTGAGAATTGTGCAGTGCTTGCAGCGTCAGAATC AGCACTGTTTTTTGTGTTGGTGAAAATATTCCATGTGCGTAAAGGGAGAGCATCAGGGACTT TGCAAATTCTTCACAAGGACCCAGAAATAGCTTAAAGATTCATGGTTTTCCTGTTGGCTTAA ATAGCCTTAATCTTTCATTTTCTACTACCATTAAGTCGGGGAAATGACATTGAACTACCTCA TTAGCAGCCTTCCCTTGATTAACTACTGACTAAAAGTGTGCTGAAAATGGCCTTTGTTTTTG TGAAGCTCATCCTATACACTAACATTTGCTTAACCATGGATTATTTTGTCTCTACAAAGCTG TGCCCTGTATTCGATTTTTACTTCAATGAGTGGTTATTGCTAGAATTCCTACAAAAAAAAAA AAAACCGTTGCAGATATTTTTGTATGTAGCTTAATAGATATTTAGTTTAAGGAGACTGCAAC ATTTGCATAAGGTGCCTAAAAACTCAAGAACCATTGATAAGTGAGATCACTCAAAATGAGCT GATATATTAAAGAAGACCTTAAAACAGTAAA (SEQ ID NO: 176) Exemplary MAN1B1 polypeptide MAACEGRRSGALGSSQSDFLTPPVGGAPWAVATTVVMYPPPPPPPHRDFISVTLSFGENYDN SKSWRRRSCWRKWKQLSRLQRNMILFLLAFLLFCGLLFYINLADHWKALAFRLEEEQKMRPE IAGLKPANPPVLPAPQKADTDPENLPEISSQKTQRHIQRGPPHLQIRPPSQDLKDGTQEEAT KRQEAPVDPRPEGDPQRTVISWRGAVIEPEQGTELPSRRAEVPTKPPLPPARTQGTPVHLNY RQKGVIDVFLHAWKGYRKFAWGHDELKPVSRSFSEWFGLGLTLIDALDTMWILGLRKEFEEA RKWVSKKLHFEKDVDVNLFESTIRILGGLLSAYHLSGDSLFLRKAEDFGNRLMPAFRTPSKI PYSDVNIGTGVAHPPRWTSDSTVAEVTSIQLEFRELSRLTGDKKFQEAVEKVTQHIHGLSGK KDGLVPMFINTHSGLFTHLGVFTLGARADSYYEYLLKQWIQGGKQETQLLEDYVEAIEGVRT HLLRHSEPSKLTFVGELAHGRFSAKMDHLVCFLPGTLALGVYHGLPASHMELAQELMETCYQ MNRQMETGLSPEIVHFNLYPQPGRRDVEVKPADRHNLLRPETVESLFYLYRVTGDRKYQDWG WEILQSFSRFTRVPSGGYSSINNVQDPQKPEPRDKMESFFLGETLKYLFLLFSDDPNLLSLD AYVFNTEAHPLPIWTPA (SEQ ID NO:177) Attorney Docket No.07039-2225WO1 / 2023-182 Nucleic acid encoding an exemplary MAN1B1 polypeptide GTTGACGGCGCTGCGATGGCTGCCTGCGAGGGCAGGAGAAGCGGAGCTCTCGGTTCCTCTCA GTCGGACTTCCTGACGCCGCCAGTGGGCGGGGCCCCTTGGGCCGTCGCCACCACTGTAGTCA TGTACCCACCGCCGCCGCCGCCGCCTCATCGGGACTTCATCTCGGTGACGCTGAGCTTTGGC GAGAACTATGACAACAGCAAGAGTTGGCGGCGGCGCTCGTGCTGGAGGAAATGGAAGCAACT GTCGAGATTGCAGCGGAATATGATTCTCTTCCTCCTTGCCTTTCTGCTTTTCTGTGGACTCC TCTTCTACATCAACTTGGCTGACCATTGGAAAGCTCTGGCTTTCAGGCTAGAGGAAGAGCAG AAGATGAGGCCAGAAATTGCTGGGTTAAAACCAGCAAATCCACCCGTCTTACCAGCTCCTCA GAAGGCGGACACCGACCCTGAGAACTTACCTGAGATTTCGTCACAGAAGACACAAAGACACA TCCAGCGGGGACCACCTCACCTGCAGATTAGACCCCCAAGCCAAGACCTGAAGGATGGGACC CAGGAGGAGGCCACAAAAAGGCAAGAAGCCCCTGTGGATCCCCGCCCGGAAGGAGATCCGCA GAGGACAGTCATCAGCTGGAGGGGAGCGGTGATCGAGCCTGAGCAGGGCACCGAGCTCCCTT CAAGAAGAGCAGAAGTGCCCACCAAGCCTCCCCTGCCACCGGCCAGGACACAGGGCACACCA GTGCATCTGAACTATCGCCAGAAGGGCGTGATTGACGTCTTCCTGCATGCATGGAAAGGATA CCGCAAGTTTGCATGGGGCCATGACGAGCTGAAGCCTGTGTCCAGGTCCTTCAGTGAGTGGT TTGGCCTCGGTCTCACACTGATCGACGCGCTGGACACCATGTGGATCTTGGGTCTGAGGAAA GAATTTGAGGAAGCCAGGAAGTGGGTGTCGAAGAAGTTACACTTTGAAAAGGACGTGGACGT CAACCTGTTTGAGAGCACGATCCGCATCCTGGGGGGGCTCCTGAGTGCCTACCACCTGTCTG GGGACAGCCTCTTCCTGAGGAAAGCTGAGGATTTTGGAAATCGGCTAATGCCTGCCTTCAGA ACACCATCCAAGATTCCTTACTCGGATGTGAACATCGGTACTGGAGTTGCCCACCCGCCACG GTGGACCTCCGACAGCACTGTGGCCGAGGTGACCAGCATTCAGCTGGAGTTCCGGGAGCTCT CCCGTCTCACAGGGGATAAGAAGTTTCAGGAGGCAGTGGAGAAGGTGACACAGCACATCCAC GGCCTGTCTGGGAAGAAGGATGGGCTGGTGCCCATGTTCATCAATACCCACAGTGGCCTCTT CACCCACCTGGGCGTATTCACGCTGGGCGCCAGGGCCGACAGCTACTATGAGTACCTGCTGA AGCAGTGGATCCAGGGCGGGAAGCAGGAGACACAGCTGCTGGAAGACTACGTGGAAGCCATC GAGGGTGTCAGAACGCACCTGCTGCGGCACTCCGAGCCCAGTAAGCTCACCTTTGTGGGGGA GCTTGCCCACGGCCGCTTCAGTGCCAAGATGGACCACCTGGTGTGCTTCCTGCCAGGGACGC TGGCTCTGGGCGTCTACCACGGCCTGCCCGCCAGCCACATGGAGCTGGCCCAGGAGCTCATG GAGACTTGTTACCAGATGAACCGGCAGATGGAGACGGGGCTGAGTCCCGAGATCGTGCACTT CAACCTTTACCCCCAGCCGGGCCGTCGGGACGTGGAGGTCAAGCCAGCAGACAGGCACAACC TGCTGCGGCCAGAGACCGTGGAGAGCCTGTTCTACCTGTACCGCGTCACAGGGGACCGCAAA TACCAGGACTGGGGCTGGGAGATTCTGCAGAGCTTCAGCCGATTCACACGGGTCCCCTCGGG TGGCTATTCTTCCATCAACAATGTCCAGGATCCTCAGAAGCCCGAGCCTAGGGACAAGATGG AGAGCTTCTTCCTGGGGGAGACGCTCAAGTATCTGTTCTTGCTCTTCTCCGATGACCCAAAC CTGCTCAGCCTGGATGCCTACGTGTTCAACACCGAAGCCCACCCTCTGCCTATCTGGACCCC TGCCTAGGGTGGATGGCTGCTGGTGTGGGGACTTCGGGTGGGCAGAGGCACCTTGCTGGGTC TGTGGCATTTTCCAAGGGCCCACGTAGCACCGGCAACCGCCAAGTGGCCCAGGCTCTGAACT GGCTCTGGGCTCCTCCTCGTCTCTGCTTTAATCAGGACACCGTGAGGACAAGTGAGGCCGTC AGTCTTGGTGTGATGCGGGGTGGGCTGGGCCGCTGGAGCCTCCGCCTGCTTCCTCCAGAAGA CACGAATCATGACTCACGATTGCTGAAGCCTGAGCAGGTCTCTGTGGGCCGACCAGAGGGGG Attorney Docket No.07039-2225WO1 / 2023-182 GCTTCGAGGTGGTCCCTGGTACTGGGGTGACCGAGTGGACAGCCCAGGGTGCAGCTCTGCCC GGGCTCGTGAAGCCTCAGATGTCCCCAATCCAAGGGTCTGGAGGGGCTGCCGTGACTCCAGA GGCCTGAGGCTCCAGGGCTGGCTCTGGTGTTTACAAGCTGGACTCAGGGATCCTCCTGGCCG CCCCGCAGGGGGCTTGGAGGGCTGGACGGCAAGTCCGTCTAGCTCACGGGCCCCTCCAGTGG AATGGGTCTTTTCGGTGGAGATAAAAGTTGATTTGCTCTAA (SEQ ID NO: 178) Example 5: Identifying Subjects as Having PMM2-CDG. A blood sample (e.g., a serum sample) obtained from a human having a CDG is assessed to determine whether the sample includes one or more of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and / or (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. If the sample includes one or more of (1)-(8) (e.g., as compared to a control sample), then the human is identified as having PMM2-CDG. Example 6: Identifying Subjects as Having a CDG that is not PMM2-CDG. A blood sample (e.g., a serum sample) obtained from a human having a CDG is assessed to determine whether the sample includes: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and Attorney Docket No.07039-2225WO1 / 2023-182 (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. If the sample lacks each of (1)-(8) (e.g., as compared to a control sample), then the human is identified as having a CDG that is not PMM2-CDG. Example 7: Treating PMM2-CDG. A blood sample (e.g., a serum sample) obtained from a human having a CDG is assessed to determine whether the sample includes one or more of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and / or (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. If the sample includes one or more of (1)-(8) (e.g., as compared to a control sample), then the human is administered, or instructed to self-administer, a PMM2 polypeptide (or nucleic acid encoding a PMM2 polypeptide) or one or more gene therapy components designed to correct an endogenous nucleic acid encoding a PMM2 polypeptide (e.g., a pathogenic PMM2 gene variant). Example 8: Treating PMM2-CDG. A blood sample (e.g., a serum sample) obtained from a human having a CDG is assessed to determine whether the sample includes one or more of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, Attorney Docket No.07039-2225WO1 / 2023-182 (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and / or (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. If the sample lacks each of (1)-(8) (e.g., as compared to a control sample), then the human is administered, or instructed to self-administer, a treatment different from a PMM2- CDG treatment. Example 9: Exemplary Embodiments. Embodiment 1. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) identifying said mammal as having a phosphomannomutase 2 (PMM2)-CDG. Embodiment 2. The method of embodiment 1, wherein said mammal is a human. Embodiment 3. The method of embodiment 1 or embodiment 2, wherein said method comprises determining the presence of (1). Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 4. The method of any one of embodiments 1-3, wherein said method comprises determining the presence of (2). Embodiment 5. The method of any one of embodiments 1-4, wherein said method comprises determining the presence of (3). Embodiment 6. The method of any one of embodiments 1-5, wherein said method comprises determining the presence of (4). Embodiment 7. The method of any one of embodiments 1-6, wherein said method comprises determining the presence of (5). Embodiment 8. The method of embodiment 7, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 9. The method of any one of embodiments 1-8, wherein said method comprises determining the presence of (6). Embodiment 10. The method of clam 9, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Embodiment 11. The method of any one of embodiments 1-10, wherein said method comprises determining the presence of (7). Embodiment 12. The method of embodiment 11, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 13. The method of any one of embodiments 1-12, wherein said method comprises determining the presence of (8). Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 14. The method of any one of embodiments 1-13, wherein said method comprises determining the presence of each of said (1)-(8). Embodiment 15. The method of any one of embodiments 1-14, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 16. The method of any one of embodiments 1-15, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Embodiment 17. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) identifying said mammal as having a CDG that is not a phosphomannomutase 2 (PMM2)-CDG. Embodiment 18. The method of embodiment 17, wherein said mammal is a human. Embodiment 19. The method of embodiment 17 or embodiment 18, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 20. The method of any one of embodiments 17-19, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 21. The method of any one of embodiments 17-20, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 22. The method of any one of embodiments 17-21, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 23. The method of any one of embodiments 17-22, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Embodiment 24. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) selecting said mammal to receive a PMM2-CDG treatment. Embodiment 25. The method of embodiment 24, wherein said PMM2-CDG treatment comprises administering a PMM2 polypeptide (or nucleic acid encoding said PMM2 polypeptide) to said mammal. Embodiment 26. The method of embodiment 25, wherein the PMM2 polypeptide comprises an amino acid set forth in SEQ ID NO:1 or a variant thereof. Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 27. The method of any one of embodiments 24-26, wherein said method further comprises administering said PMM2-CDG treatment to said mammal. Embodiment 28. The method of any one of embodiments 24 – 27, wherein said mammal is a human. Embodiment 29. The method of any one of embodiments 24-28, wherein said method comprises determining the presence of (1). Embodiment 30. The method of any one of embodiments 24-29, wherein said method comprises determining the presence of (2). Embodiment 31. The method of any one of embodiments 24-30, wherein said method comprises determining the presence of (3). Embodiment 32. The method of any one of embodiments 24-31, wherein said method comprises determining the presence of (4). Embodiment 33. The method of any one of embodiments 24-32, wherein said method comprises determining the presence of (5). Embodiment 34. The method of embodiment 33, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 35. The method of any one of embodiments 24-34, wherein said method comprises determining the presence of (6). Embodiment 36. The method of clam 35, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 37. The method of any one of embodiments 24-36, wherein said method comprises determining the presence of (7). Embodiment 38. The method of embodiment 37, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 39. The method of any one of embodiments 24-38, wherein said method comprises determining the presence of (8). Embodiment 40. The method of any one of embodiments 24-39, wherein said method comprises determining the presence of each of said (1)-(8). Embodiment 41. The method of any one of embodiments 24-40, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 42. The method of any one of embodiments 24-41, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Embodiment 43. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and Attorney Docket No.07039-2225WO1 / 2023-182 (b) selecting said mammal to receive a CDG treatment that is not a PMM2-CDG treatment. Embodiment 44. The method of embodiment 43, wherein said CDG treatment comprises administering one or more monosaccharides or derivatives thereof to said mammal. Embodiment 45. The method of embodiment 44, wherein said one or more monosaccharides or derivatives thereof comprise one or more of galactose, mannose, and mannose-1-phosphate. Embodiment 46. The method of any one of embodiments 43-45, wherein said method further comprises administering said CDG treatment to said mammal. Embodiment 47. The method of any one of embodiments 43-46, wherein said mammal is a human. Embodiment 48. The method of any one of embodiments 43-47, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 49. The method of any one of embodiments 43-48, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Embodiment 50. The method of any one of embodiments 43-49, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 51. The method of any one of embodiments 43-50, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 52. The method of any one of embodiments 43-51, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 53. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) administering a PMM2-CDG treatment to said mammal. Embodiment 54. The method of embodiment 53, wherein said PMM2-CDG treatment comprises administering a PMM2 polypeptide (or nucleic acid encoding said PMM2 polypeptide) to said mammal. Embodiment 55. The method of embodiment 54, wherein the PMM2 polypeptide comprises an amino acid set forth in SEQ ID NO:1 or a variant thereof. Embodiment 56. The method of any one of embodiments 53 – 55, wherein said mammal is a human. Embodiment 57. The method of any one of embodiments 53 – 56, wherein said method comprises determining the presence of (1). Embodiment 58. The method of any one of embodiments 53-57, wherein said method comprises determining the presence of (2). Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 59. The method of any one of embodiments 53-58, wherein said method comprises determining the presence of (3). Embodiment 60. The method of any one of embodiments 53-59, wherein said method comprises determining the presence of (4). Embodiment 61. The method of any one of embodiments 53-60, wherein said method comprises determining the presence of (5). Embodiment 62. The method of embodiment 61, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 63. The method of any one of embodiments 53-62, wherein said method comprises determining the presence of (6). Embodiment 64. The method of clam 63, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Embodiment 65. The method of any one of embodiments 53-64, wherein said method comprises determining the presence of (7). Embodiment 66. The method of embodiment 65, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 67. The method of any one of embodiments 53-66, wherein said method comprises determining the presence of (8). Embodiment 68. The method of any one of embodiments 53-67, wherein said method comprises determining the presence of each of said (1)-(8). Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 69. The method of any one of embodiments 53-68, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 70. The method of any one of embodiments 53-69, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Embodiment 71. A method for treating a CDG, wherein said method comprises administering a PMM2-CDG treatment to a mammal that was identified as having a blood sample comprising the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. Embodiment 72. The method of embodiment 71, wherein said PMM2-CDG treatment comprises administering a PMM2 polypeptide (or nucleic acid encoding said PMM2 polypeptide) to said mammal. Embodiment 73. The method of embodiment 72, wherein the PMM2 polypeptide comprises an amino acid set forth in SEQ ID NO:1 or a variant thereof. Embodiment 74. The method of any one of embodiments 71 – 73, wherein said mammal is a human. Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 75. The method of any one of embodiments 71 – 74, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (1). Embodiment 76. The method of any one of embodiments 71-75, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (2). Embodiment 77. The method of any one of embodiments 71-76, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (3). Embodiment 78. The method of any one of embodiments 71-77, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (4). Embodiment 79. The method of any one of embodiments 71-78, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (5). Embodiment 80. The method of embodiment 79, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 81. The method of any one of embodiments 71-80, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (6). Embodiment 82. The method of clam 81, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Embodiment 83. The method of any one of embodiments 71-82, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (7). Embodiment 84. The method of embodiment 83, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 85. The method of any one of embodiments 71-84, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of (8). Embodiment 86. The method of any one of embodiments 71-85, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of each of said (1)-(8). Embodiment 87. The method of any one of embodiments 71-86, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 88. The method of any one of embodiments 71-87, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Embodiment 89. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) administering a CDG treatment that is not a PMM2-CDG treatment to said mammal. Embodiment 90. The method of embodiment 89, wherein said CDG treatment comprises administering one or more monosaccharides or derivatives thereof to said mammal. Attorney Docket No.07039-2225WO1 / 2023-182 Embodiment 91. The method of embodiment 90, wherein said one or more monosaccharides or derivatives thereof comprise one or more of galactose, mannose, and mannose-1-phosphate. Embodiment 92. The method of any one of embodiments 89 – 91, wherein said mammal is a human. Embodiment 93. The method of any one of embodiments 89 – 92, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 94. The method of any one of embodiments 89-93, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Embodiment 95. The method of any one of embodiments 89-94, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 96. The method of any one of embodiments 89-95, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 97. The method of any one of embodiments 89-96, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Embodiment 98. A method for treating CDG, wherein said method comprises administering a CDG treatment that is not a PMM2-CDG treatment to a mammal that was identified as having a blood sample that lacks the presence of each of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, Attorney Docket No.07039-2225WO1 / 2023-182 (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide. Embodiment 99. The method of embodiment 98, wherein said CDG treatment comprises administering one or more monosaccharides or derivatives thereof to said mammal. Embodiment 100. The method of embodiment 99, wherein said one or more monosaccharides or derivatives thereof comprise one or more of galactose, mannose, and mannose-1-phosphate. Embodiment 101. The method of any one of embodiments 98 – 100, wherein said mammal is a human. Embodiment 102. The method of any one of embodiments 98 – 101, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207. Embodiment 103. The method of any one of embodiments 98-102, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207. Embodiment 104. The method of any one of embodiments 98-103, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207. Embodiment 105. The method of any one of embodiments 98-104, wherein each Hex in said (1)-(8) is a mannose (Man). Embodiment 106. The method of any one of embodiments 98-105, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc). Attorney Docket No.07039-2225WO1 / 2023-182 OTHER EMBODIMENTS It is to be understood that while the invention has been described in conjunction with the detailed description thereof, the foregoing description is intended to illustrate and not limit the scope of the invention, which is defined by the scope of the appended claims. Other aspects, advantages, and modifications are within the scope of the following claims.

Claims

Attorney Docket No.07039-2225WO1 / 2023-182 WHAT IS CLAIMED IS:

1. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) identifying said mammal as having a phosphomannomutase 2 (PMM2)-CDG.

2. The method of claim 1, wherein said mammal is a human.

3. The method of claim 1, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

4. The method of clam 1, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

5. The method of claim 1, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.

6. The method of any one of claims 1-5, wherein said method comprises determining the presence of each of said (1)-(8).Attorney Docket No.07039-2225WO1 / 2023-182 7. The method of any one of claims 1-5, wherein each Hex in said (1)-(8) is a mannose (Man).

8. The method of any one of claims 1-5, wherein each HexNAc in said (1)-(8) is an N- acetylglucosamine (GlcNAc).

9. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) identifying said mammal as having a CDG that is not a phosphomannomutase 2 (PMM2)-CDG.

10. The method of claim 9, wherein said mammal is a human.

11. The method of claim 9 or claim 10, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

12. The method of claim 9 or claim 10, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

13. The method of claim 9 or claim 10, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.Attorney Docket No.07039-2225WO1 / 2023-182 14. The method of claim 9 or claim 10, wherein each Hex in said (1)-(8) is a mannose (Man).

15. The method of claim 9 or claim 10, wherein each HexNAc in said (1)-(8) is an N- acetylglucosamine (GlcNAc).

16. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) selecting said mammal to receive a PMM2-CDG treatment.

17. The method of claim 16, wherein said PMM2-CDG treatment comprises administering a PMM2 polypeptide (or nucleic acid encoding said PMM2 polypeptide) to said mammal.

18. The method of claim 17, wherein the PMM2 polypeptide comprises an amino acid set forth in SEQ ID NO:1 or a variant thereof.

19. The method of any one of claims 16-17, wherein said method further comprises administering said PMM2-CDG treatment to said mammal.Attorney Docket No.07039-2225WO1 / 2023-182 20. The method of any one of claims 16-17, wherein said mammal is a human.

21. The method of claim 16, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

22. The method of clam 16, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

23. The method of claim 16, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.

24. The method of any one of claims 16-23, wherein said method comprises determining the presence of each of said (1)-(8).

25. The method of any one of claims 16-23, wherein each Hex in said (1)-(8) is a mannose (Man).

26. The method of any one of claims 16-23, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc).

27. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide,Attorney Docket No.07039-2225WO1 / 2023-182 (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) selecting said mammal to receive a CDG treatment that is not a PMM2-CDG treatment.

28. The method of claim 27, wherein said CDG treatment comprises administering one or more monosaccharides or derivatives thereof to said mammal.

29. The method of claim 28, wherein said one or more monosaccharides or derivatives thereof comprise one or more of galactose, mannose, and mannose-1-phosphate.

30. The method of any one of claims 27-29, wherein said method further comprises administering said CDG treatment to said mammal.

31. The method of any one of claims 27-29, wherein said mammal is a human.

32. The method of any one of claims 27-29, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

33. The method of any one of claims 27-29, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

34. The method of any one of claims 27-29, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.

35. The method of any one of claims 27-29, wherein each Hex in said (1)-(8) is a mannose (Man).

36. The method of any one of claims 27-29, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc).Attorney Docket No.07039-2225WO1 / 2023-182 37. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; and (b) administering a PMM2-CDG treatment to said mammal.

38. The method of claim 37, wherein said PMM2-CDG treatment comprises administering a PMM2 polypeptide (or nucleic acid encoding said PMM2 polypeptide) to said mammal.

39. The method of claim 37, wherein the PMM2 polypeptide comprises an amino acid set forth in SEQ ID NO:1 or a variant thereof.

40. The method of any one of claims 37-39, wherein said mammal is a human.

41. The method of claim 37, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

42. The method of clam 37, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

43. The method of claim 37, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.Attorney Docket No.07039-2225WO1 / 2023-182 44. The method of any one of claims 37-43, wherein said method comprises determining the presence of each of said (1)-(8).

45. The method of any one of claims 37-43, wherein each Hex in said (1)-(8) is a mannose (Man).

46. The method of any one of claims 37-43, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc).

47. A method for treating a CDG, wherein said method comprises administering a PMM2-CDG treatment to a mammal that was identified as having a blood sample comprising the presence of at least one of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide.

48. The method of claim 47, wherein said PMM2-CDG treatment comprises administering a PMM2 polypeptide (or nucleic acid encoding said PMM2 polypeptide) to said mammal.

49. The method of claim 47, wherein the PMM2 polypeptide comprises an amino acid set forth in SEQ ID NO:1 or a variant thereof.

50. The method of any one of claims 47-49, wherein said mammal is a human.Attorney Docket No.07039-2225WO1 / 2023-182 51. The method of claim 47, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

52. The method of clam 47, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

53. The method of claim 47, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.

54. The method of any one of claims 47-53, wherein said mammal is a mammal that was identified as having a blood sample comprising the presence of each of said (1)-(8).

55. The method of any one of claims 47-53, wherein each Hex in said (1)-(8) is a mannose (Man).

56. The method of any one of claims 47-53, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc).

57. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal lacks the presence of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide, (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide; andAttorney Docket No.07039-2225WO1 / 2023-182 (b) administering a CDG treatment that is not a PMM2-CDG treatment to said mammal.

58. The method of claim 57, wherein said CDG treatment comprises administering one or more monosaccharides or derivatives thereof to said mammal.

59. The method of claim 57, wherein the one or more monosaccharides or derivatives thereof comprise one or more of galactose, mannose, and mannose-1-phosphate.

60. The method of any one of claims 57-59, wherein said mammal is a human.

61. The method of claim 57, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

62. The method of claim 57, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

63. The method of claim 57, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.

64. The method of any one of claims 57-63, wherein each Hex in said (1)-(8) is a mannose (Man).

65. The method of any one of claims 57-63, wherein each HexNAc in said (1)-(8) is an N-acetylglucosamine (GlcNAc).

66. A method for treating CDG, wherein said method comprises administering a CDG treatment that is not a PMM2-CDG treatment to a mammal that was identified as having a blood sample that lacks the presence of each of: (1) an elevated level of a C4 (Asn226: Hex5HexNAc2) polypeptide, (2) an elevated level of an ORM1 (Asn103: Hex1HexNAc2) polypeptide,Attorney Docket No.07039-2225WO1 / 2023-182 (3) an elevated level of an ORM2 (Asn103: Hex1HexNAc2) polypeptide, (4) an elevated level of an F12 (Asn249: Hex1HexNAc2) polypeptide, (5) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide, (6) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide, (7) an elevated level of a HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide, and (8) an elevated level of a C7 (Asn202: Hex3HexNAc2) polypeptide.

67. The method of claim 66, wherein said CDG treatment comprises administering one or more monosaccharides or derivatives thereof to said mammal.

68. The method of claim 66, wherein the one or more monosaccharides or derivatives thereof comprise one or more of galactose, mannose, and mannose-1-phosphate.

69. The method of any one of claims 66-68, wherein said mammal is a human.

70. The method of claim 66, wherein said HP (Asn211: Hex5HexNAc4NeuAc2Fuc1) polypeptide is not glycosylated at Asn207.

71. The method of claim 66, wherein said HP (Asn211: Hex5HexNAc4NeuAc2) polypeptide is not glycosylated at Asn207.

72. The method of claim 66, wherein said HP (Asn211: Hex5HexNAc4NeuAc1) polypeptide is not glycosylated at Asn207.

73. The method of claim 66, wherein each Hex in said (1)-(8) is a mannose (Man).

74. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of:Attorney Docket No.07039-2225WO1 / 2023-182 (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide; (2) an elevated level of an alpha-2-HS-glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide; and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide; and (b) identifying said mammal as having a mannose phosphate isomerase (MPI)-CDG.

75. The method of claim 74, wherein said mammal is a human.

76. The method of any one of claims 74-75, wherein each Hex in said (1)-(4) is a mannose (Man).

77. The method of any one of claims 74-75, wherein each HexNAc in said (1)-(4) is an N-acetylglucosamine (GlcNAc).

78. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide; (2) an elevated level of an alpha-2-HS-glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide; and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide; and (b) selecting said mammal to receive a MPI-CDG treatment.Attorney Docket No.07039-2225WO1 / 2023-182 79. The method of claim 78, wherein said MPI-CDG treatment comprises administering a MPI polypeptide (or nucleic acid encoding said MPI polypeptide) to said mammal.

80. The method of claim 79, wherein the MPI polypeptide comprises an amino acid set forth in SEQ ID NO:173 or a variant thereof.

81. The method of any one of claims 78-80, wherein said method further comprises administering said MPI-CDG treatment to said mammal.

82. The method of any one of claims 78-81, wherein said mammal is a human.

83. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 2 (IGHG2) (Asn176: Hex5HexNAc3NeuAc1Fuc2) polypeptide; (2) an elevated level of an alpha-2-HS-glycoprotein (AHSG) (Asn176:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex2HexNAc2) polypeptide; and (4) an elevated level of a factor 12 (Asn249:Hex1HexNAc2) polypeptide; and (b) administering a MPI-CDG treatment to said mammal.

84. The method of claim 83, wherein said MPI-CDG treatment comprises administering a MPI polypeptide (or nucleic acid encoding said MPI polypeptide) to said mammal.

85. The method of claim 84, wherein the MPI polypeptide comprises an amino acid set forth in SEQ ID NO:173 or a variant thereof.

86. The method of any one of claims 83-85, wherein said mammal is a human.Attorney Docket No.07039-2225WO1 / 2023-182 87. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide or an apoB100 (Asn3465:Hex3HexNAc3) polypeptide; (2) an elevated level of an alpha-2-macroglobulin (?2M) (Asn869:Hex3HexNAc2) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide; and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide; and (b) identifying said mammal as having a steroid 5-alpha-reductase 3 (SRD5A3)- CDG.

88. The method of claim 87, wherein said mammal is a human.

89. The method of any one of claims 87-88, wherein each Hex in said (1)-(4) is a mannose (Man).

90. The method of any one of claims 87-88, wherein each HexNAc in said (1)-(4) is an N-acetylglucosamine (GlcNAc).

91. The method of any one of claims 87-90, wherein said HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide is not glycosylated at Asn207.

92. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of:Attorney Docket No.07039-2225WO1 / 2023-182 (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide or an apoB100 (Asn3465:Hex3HexNAc3) polypeptide; (2) an elevated level of an alpha-2-macroglobulin (?2M) (Asn869:Hex3HexNAc2) polypeptide; (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide; and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide; and (b) selecting said mammal to receive a SRD5A3-CDG treatment.

93. The method of claim 92, wherein said SRD5A3-CDG treatment comprises administering a SRD5A3polypeptide (or nucleic acid encoding said SRD5A3 polypeptide) to said mammal.

94. The method of claim 93, wherein the SRD5A3 polypeptide comprises an amino acid set forth in SEQ ID NO:175 or a variant thereof.

95. The method of any one of claims 92-94, wherein said method further comprises administering said SRD5A3-CDG treatment to said mammal.

96. The method of any one of claims 92-95, wherein said mammal is a human.

97. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an apolipoprotein B-100 (apoB100) (Asn3465:Hex3HexNAc2) polypeptide or an apoB100 (Asn3465:Hex3HexNAc3) polypeptide; (2) an elevated level of an alpha-2-macroglobulin (?2M) (Asn869:Hex3HexNAc2) polypeptide;Attorney Docket No.07039-2225WO1 / 2023-182 (3) an elevated level of a complement C4 (Asn226:Hex5HexNAc2) polypeptide; and (4) an elevated level of a HP (Asn211:Hex4HexNAc3NeuAc1) polypeptide; and (b) administering a SRD5A3-CDG treatment to said mammal.

98. The method of claim 97, wherein said SRD5A3-CDG treatment comprises administering a SRD5A3 polypeptide (or nucleic acid encoding said SRD5A3 polypeptide) to said mammal.

99. The method of claim 98, wherein the SRD5A3 polypeptide comprises an amino acid set forth in SEQ ID NO:175 or a variant thereof.

100. The method of any one of claims 97-99, wherein said mammal is a human.

101. A method for assessing a mammal having a congenital disorder of glycosylation (CDG), wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) polypeptide or an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide; (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide; and (4) an elevated level of a C4B-binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide; and (b) identifying said mammal as having a mannosyl-oligosaccharide 1,2-alpha- mannosidase (MAN1B1)-CDG.

102. The method of claim 101, wherein said mammal is a human.Attorney Docket No.07039-2225WO1 / 2023-182 103. The method of any one of claims 101-102, wherein each Hex in said (1)-(4) is a mannose (Man).

104. The method of any one of claims 101-102, wherein each HexNAc in said (1)-(4) is an N-acetylglucosamine (GlcNAc).

105. A method for selecting a treatment for a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) polypeptide or an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide; (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide; and (4) an elevated level of a C4B-binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide; and (b) selecting said mammal to receive a MAN1B1-CDG treatment.

106. The method of claim 105, wherein said MAN1B1-CDG treatment comprises administering a MAN1B1 polypeptide (or nucleic acid encoding said MAN1B1 polypeptide) to said mammal.

107. The method of claim 106, wherein the MAN1B1 polypeptide comprises an amino acid set forth in SEQ ID NO:177 or a variant thereof.

108. The method of any one of claims 105-107, wherein said method further comprises administering said MAN1B1-CDG treatment to said mammal.Attorney Docket No.07039-2225WO1 / 2023-182 109. The method of any one of claims 105-108, wherein said mammal is a human.

110. A method for treating a mammal having a CDG, wherein said method comprises: (a) determining that a blood sample from said mammal contains the presence of at least one of: (1) an elevated level of an immunoglobulin heavy chain constant gamma 1 (IGHG1) (Asn180:Hex6HexNAc3NeuAc1) polypeptide or an IGHG1 (Asn180:Hex6HexNAc3NeuAc1Fuc1) polypeptide; (2) an elevated level of an apoB100 (Asn3224:Hex6HexNAc3NeuAc1) polypeptide; (3) an elevated level of an albumin (Asn123:Hex6HexNAc3NeuAc1) polypeptide; and (4) an elevated level of a C4B-binding protein beta chain (Asn64:Hex6HexNAc3NeuAc1) polypeptide; and (b) administering a MAN1B1-CDG treatment to said mammal.

111. The method of claim 110, wherein said MAN1B1-CDG treatment comprises administering a MAN1B1polypeptide (or nucleic acid encoding said MAN1B1polypeptide) to said mammal.

112. The method of claim 111, wherein the MAN1B1polypeptide comprises an amino acid set forth in SEQ ID NO:177 or a variant thereof.

113. The method of any one of claims 110-112, wherein said mammal is a human.

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