78 results about "Classic phenylketonuria" patented technology

A nutritional formula for PKU patients. The nutritional formula has, as a protein source, a mixture of caseino-glyco-macropeptide and complementary essential amino acids other than Phe to provide a balanced amino acid profile. Vitamins and minerals sufficient to meet daily requirements are also included. When used as a complete diet, the nutritional formula includes a carbohydrate source and a fat source. However the nutrutional formula may also be used as a protein supplement in which case the carbohydrate source and the fat source may be omitted. The nutritional formula has a pleasant taste.

Provided herein are phenylalanine ammonia-lyase (PAL) variants produced by prokaryotes, wherein such prokaryotic PAL variant has a greater phenylalanine-converting activity and / or a reduced immunogenicity as compared to a wild-type PAL. Further provided are compositions of prokaryotic PAL and biologically active fragments, mutants, variants or analogs thereof, as well as methods for the production, purification, formulation, and use of such compositions for industrial and therapeutic purposes, e.g., treating hyperphenylalaninemia, including phenylketonuria, and other disorders, including cancer.

The present invention provides, among other things, methods of treating phenylketonuria (PKU), including administering to a subject in need of treatment a composition comprising an mRNA encoding phenylalanine hydroxylase (PAH) at an effective dose and an administration interval such that at least one symptom or feature of PKU is reduced in intensity, severity, or frequency or has delayed in onset. In some embodiments, the mRNA is encapsulated in a liposome comprising one or more cationic lipids, one or more non-cationic lipids, one or more cholesterol-based lipids and one or more PEG-modified lipids

The present invention is directed to a novel methods and compositions for the therapeutic intervention in hyperphenylalaninemia. More specifically, the specification describes methods and compositions for treating various types of phenylketonurias using compositions comprising BH4. Combination therapies of BH4 and other therapeutic regimens are contemplated.

The invention provides formula powder for phenylketonuria children and a preparation method thereof. The formula powder comprises solid glucose syrup, amino acid, fatty acid, nucleotide, fish oil, dietary fiber, composite vitamins, composite mineral substances and an emulsifier, and is prepared by using a wet-method preparation process of materials. According to the formula powder, special free amino acid is adopted, a proper amount of free L-tyrosine is screened and optimized, and phenylalanine is removed, so that the physiological needs of sick children are met, and at the same time hypersensitivity of phenylketonuria infants is effectively prevented; in the formula, the components have the mutual synergistic effect, the powder is approximate to breast milk in absorption, taste and the like, children can absorb sufficient nutrition after taking the powder, and meanwhile anaphylaxis such as diarrhea can be effectively reduced; and the formula powder is simple in preparation method and applicable to requirements of large-scale industrial production.

Disclosed is a composition that includes a tetrahydrobiopterin in a controlled-release pharmaceutical preparation. Also disclosed is a method of treating a patient with phenylketonuria that includes administering, to the patient, a composition that contains tetrahydrobiopterin in a controlled-release pharmaceutical preparation. Also disclosed is a method of treating a patient with ADHD that includes administering a tetrahydropterin to the patient. Compositions for the treatment of ADHD are also described.

Medical foods containing glycomacroprotein and additional supplemented amounts of arginine, leucine, and optionally other amino acids, such as tyrosine, are disclosed. The medical foods can be used to provide the complete protein requirements for patients having metabolic disorders such as phenylketonuria.

The invention discloses a new system for screening and diagnosing phenylketonuria.41 common phenylalanine hydroxylase gene mutation sites and 4 most common 6-pyruvoyl tetrahydrobiopterin synthetase (PTPS) gene (PTS) mutation sites are screened to form the gene mutation detection system of phenylketonuria.The system is low in cost and high in throughput.Compared with the prior art, the system has the advantages that most mutation sites can be detected in one system, and 45 mutation sites can be detected; the comprehensive cost is the lowest, and the total cost of the system is lower than built methods using the DNA chip technology, the 'molecular switch' technology, the high-resolution melting curve method and the SNaPShot technology to detect PAH gene mutation; most mutation sites can be detected, the number of the detected mutation sites is twice as the number of the detected PAH gene mutation sites of the high-resolution melting curve method built by Xiamen University, the number of the detected mutation sites is 4 times as the number of the detected mutation sites of the DNA chip technology and the SNaPShot technology, and the number of the detected mutation sites is 6 times as the number of the detected mutation sites of the 'molecular switch' technology.

The invention relates to a kit for detecting 7 hot mutant sites of a phenylketonuria PAH gene and a PCR amplification method thereof. The invention is characterized in that in the PCR reaction in which high-fidelity DNA polymerase participates, the product of a mutation detection primer which is modified in a 3'-5' exonuclease digestion resistance way, has very high specificity, and people can directly observe the existence of the strips obtained by gel electrophoresis to judge the genotype of the corresponding mutant sites of the PAH gene. The invention has the advantages of simple operation and economical performance, does not need sequencing, and can be operated in a common molecular biology laboratory. The method of the invention is combined with the fluorescence quantitative PCR technology, and can realize automation and high flux of clinic detection of the biological sample, thereby greatly enhancing the detection accuracy and efficiency.

Disclosed is a composition that includes a tetrahydrobiopterin in a controlled-release pharmaceutical preparation. Also disclosed is a method of treating a patient with phenylketonuria that includes administering, to the patient, a composition that contains tetrahydrobiopterin in a controlled-release pharmaceutical preparation. Also disclosed is a method of treating a patient with ADHD that includes administering a tetrahydropterin to the patient. Compositions for the treatment of ADHD are also described.

The invention discloses a PKU (Phenylketnuria) gene detection kit. According to the kit, a multiple ligase detection reaction (MLDR) technology is adopted, specific probes and label probes on seven polymorphic sites on PKU determining genes (PAH) are adopted, the genotypes of seven common polymorphic sites on the PAH genes in Chinese population are detected, the genotypes of four or five detected samples can be simultaneously and accurately judged by utilizing a multiple fluorescent capillary electrophoresis detection technology, and the phenylketonuria can be diagnosed and screened. The kit disclosed by the invention can be used for rapidly and efficiently detecting the genotypes of seven polymorphic sites on the PAH genes and is a rapid, simple, convenient, economical and high-efficiency PKU gene screening and diagnosing kit.

The invention discloses a kit for synchronously detecting 12 mutation hotspots of the Chinese population phenylketonuria PAH (phenylalanine hydroxylase) gene. In the kit, 12 loca on the Chinese population PAH gene are used as detection objects; an amplification primer and an extension primer are respectively designed for the mutation type of each locus; each destination section is subjected to PCR amplification and mark extension at the same time; and the gene types of the 12 mutation hotspots are obtained at the same time through capillary electrophoresis analysis. The invention provides a phenylketonuria PAH gene mutation screening kit which is simple, has the advantages of high flux, high performance, low cost and high detection accuracy, is suitable for the Chinese people and suitable for the group screening of the Chinese population phenylketonuria.

The invention discloses a PKU (Phenylketonuria) pathogenic gene mutation detection method and device based on semiconductor sequencing. A local mutation database is constructed to comprehensively reflect background noise which possibly exists in a detection range and true and false positive results of mutation can be effectively distinguished; the problem that the background noises of PKU detection are great, caused by inherent homopolymerize basic group sequencing errors of a semiconductor sequencing platform, is solved; influences of different batches sequencing quality can be controlled relatively well and the accuracy and stability of detection are improved; the PKU pathogenic gene mutation detection method and device are especially suitable for a Proton platform.

A yeast in the form of micro capsule for controlling the release of protein medicine to treat uremia, hepatal failure, phenylketonuria, cancer, etc has the sodium alginate-chitosan-sodium alginate structure, and the yeast is dispersed proportionally in the liquid contained in the micro capsule.

The invention discloses a set of primer group and a detection method capable of simultaneously detecting relevant gene mutation of mediterranean anemia, epicophosis, phenylketonuria and hepatolenticular degeneration. The primer group is composed of a primer pool 1 comprising 9 pairs of primers, a primer pool 2 comprising 10 pairs of primers, and a primer pool 3 comprising 8 pairs of primers, wherein upstream and downstream primer sequences are sequentially shown as SEQ ID NO.1-54. The three primer pools of the primer group can carry out multiplex PCR amplification simultaneously, in combination with a high-throughput sequencing technology, common pathopoiesis mutation sites capable of simultaneously detecting the four genetic diseases including mediterranean anemia, epicophosis, phenylketonuria and hepatolenticular degeneration are established, and in addition, the method is efficient, rapid and accurate, is good in repeatability, and has a very good application prospect.

The present invention relates to a method for preparing a recombinant Phe-free or Phe-low protein, the method comprising using B. subtilis or B. licheniformis as an expression system and / or a recombinant host cell into which a nucleotide encoding a recombinant Phe-free or Phe-low protein has been inserted into the genome.

The invention discloses a kit for detecting a PAH (phenylalanine hydroxylase) gene of phenylketonuria. The kit comprises (1) a gene chip with 13 mutation sites of the PAH gene and a normal control complementary nucleotide sequence probe thereof and (2) various primers for amplifying DNA sequences in clinical samples, wherein the probe is SEQ ID Nos: 1-26 or the sequence complementary to SEQ ID Nos: 1-26; the DNA sequences of the primers are SEQ ID Nos: 27-40. By virtue of the kit for detecting the PAH gene, which is disclosed by the invention, a joint detection platform for detecting 13 common mutation sites of the PAH gene is provided, a synchronous joint detection is achieved, the specificity of the detection is improved, the cost is reduced and the detection time is shortened; the kit is of great significance for screening phenylketonuria-infected patients and carrying out genetic counseling and prenatal diagnosis.

The invention discloses a detection kit of gene mutations associated with phenylketonuria. The detection kit comprises ddH2O, 10*buffer (Takara), 2*GC buffer I, dNTP, MgCl2, HSTaq, a multiple PCR mixed primer liquid and an Illumina I5 / I7 primer. The detection kit has a wide detection range, comprehensively detects phenylketonuria caused by five gene defects, sequencing detection is conducted on the upstream 500bp of a genetic transcription start site, 5'UTR, a coding region, 8pp intron sequences of a splice site and transcription terminators, it is predicted that the mutation detection rate can reach 95% or above, and the detection kit can be better applied to clinical practice.

A method of conveniently and quickly quantitating subject substances which comprises using as reaction reagents at least dehydrogenases specific respectively to branched amino acids containing D-galactose and L-leucine and phenylalanine, which are the substances contained in biological samples to be assayed, coenzymes, an electron mediator and a tetrazolium salt and detecting formazan, which has been finally formed depending on the concentrations of the subject substances by the enzymatic reactions and oxidation reactions of the biological samples with the reaction reagents, by using both or one of an optical detection procedure and an electrochemical detection procedure, thereby embodying a convenient and quick examination of three diseases with inborn errors of metabolism, i.e., galactosemia, maple syrup urine disease and phenylketonuria.

The invention discloses a probe for detecting common genetic diseases, a gene chip, a preparation method and application. The preparation method comprises the following steps of according to genes ofthalassemia, phenylketonuria, spinal muscular atrophy, hepatolenticular degeneration, pseudomuscular hypertrophy, glycogen storage disease Type II, methylmalonic academia, methylmalonic aciduria-accompanied type cysteine peptiduria Type cb1C, and oculocutaneous albinism Type 1, constructing a target capturing area, and designing a capturing probe, wherein the target capturing area comprises all globin genes, important regulating areas, deleted mutation breakpoints and SNP (single nucleotide polymorphism) sites of alpha and beta genes, and SMN1, PAH, ATP7B, DMD, GAA, MUT, MMACHC and TYR genes.The probe for the gene mutation of common genetic diseases can be designed according to the related genes of nine types of genetic diseases, and the prepared probe can be used for detecting the nine types of genetic diseases, and be suitable for large-scale population diagnosis and screening.

The invention belongs to the technical field of biology and particularly relates to a kit for detecting whether pathogenic genes of phenylketonuria are mutated. The kit contains the following main components: (1) 13 pairs of PCR (Polymerase Chain Reaction) amplification and sequencing primers of 1-13 exon areas of PAH (Polycyclic Aromatic Hydrocarbon) genes; (2) PCR amplification reagent; (3) PCR product purifying reagent; and (4) DNA sequencing reagent. The kit is used for detecting mutants of the PAH genes of the pathogenic genes of the phenylketonuria, and has the advantages that carriers and patients with the pathogenic genes can be rapidly and conveniently checked, the benefit for prenatal diagnosis and early stoppage of birthing of child patients is achieved, and the morbidity of the phenylketonuria is reduced.

The invention discloses a synthesizing method of methyl difluoride ether and amine, which is characterized by the following: neutralizing soluble organic solvent at 50-80 deg.c; reacting compound with monohydric hydrogen or nitrogen atom on the hydrogen and univalent metal hydroxide compound solution and difluo-monochloromethyl phenylketonuria or difluo-monochloromethyl phenylsulfone for 1-5h to produce the product with hydrogen replaced by fluorine methyl.

The invention discloses a mutant of phenylalanine deaminase with an anabaena source and belongs to protein engineering. The phenylalanine deaminase E75L obtained in the invention has trypsin degradation resistance and low pH resistance which are greatly improved compared with those of wild-type enzymes. The phenylalanine deaminase E75L provided by the invention achieves the effect of promoting application of the phenylalanine deaminase in oral medication of phenylketonuria (PKU) to a certain degree.

Disclosed are methods for treating a subject suffering from phenylketonuria and / or phenylalanemia. The methods include, in part, enterally administering to the subject a LNAA supplement in which the weight ratio of Leu to Val is greater than 2:1; in which the weight ratio of Leu to iLeu is greater than 3:1; or which includes one or more LNAAs and which further includes Lys. LNAA supplements are also disclosed. Also disclosed are methods for treating a subject suffering from a condition involving a metabolic disorder involving the metabolism of a first amino acid X. The method includes enterally administering to the subject a composition which (i) is substantially free from the first amino acid X and (ii) which includes a second amino acid Y that competes with amino acid X at a gastrointestinal tract transporter.

Disclosed is a method for preparing a composition enriched for receptors (typically molecular impringet polymers, MIPs) that bind an agent, where said receptors each specifically bind at least two discrete sites on said agent, by subjecting a sample of receptors to a first step of affinity purification with the agent where one binding site on the agent is non-accessible for binding to the receptors and subsequently subjecting the purified receptors to at least one further step of affinity purification with the agent where a second binding site on the agent is non-accessible. Also disclosed is a method for treatment, amelioration or prophylaxis of a disease selected from the group consisting of phenylketonuria (PKU, Følling's disease), hyperphenylalaninemia (HPA), alcaptonuria (black urine disease), tyrosinemia, hypertyrosinemia, myasthenia gravis, histidinemia, urocanic aciduria, maple syrup urine disease (MSUD), isovaleric acidemia (isovaleryl-CoA dehydrogenase deficiency), homocystinuria, propionic acidemia, methylmalonic acidemia, and glutaric aciduria Type 1 (GA-I), galactosemia, comprising administering to the gastrointestinal tract of a patient in need thereof an effective amount of a composition of molecular imprinted polymers (MIPs), said composition being capable of binding a symptom provoking agent of said disease.

The present invention provides Phenylalanine Hydroxylase (PAH) fusion proteins and pharmaceutical compositions comprising the same, as well as encoding polynucleotides and vectors, and methods for treating hyperphenylalaninemia, including PKU, by enzyme replacement therapy. The fusion proteins have phenylalanine hydroxylase activity when administered: and have an increased half-life or persistence in circulation, as compared to unfused counterparts. The PAH fusion proteins are suitable for enzyme replacement therapy in PKU patients by converting phenylalanine in the circulation to tyrosine, thereby controlling phenylalanine levels.

The invention discloses a phenylketonuria detection primer group, a kit and a gene mutation detection method. The primer group covering six phenylketonuria related genes PAH, PTS, GCH1, QDPR, PCBD1 and SPR and upstream and downstream 10bp splice sites thereof are provided for the first time. The primer group in a multiplex PCR (polymerase chain reaction) reaction system is high in specificity, lowin primer mutual interference, high in uniformity and high in amplicon expression depth. The phenylketonuria detection primer group, the kit and the gene mutation detection method have advantages ofquickness, comprehensiveness, accuracy and simplicity in operation and are applicable to detection of samples of blood, blood spots, leukocytes and the like. Compared with the prior art, the phenylketonuria detection primer group, the kit and the gene mutation detection method have advantages of wide coverage, more detection sites and high accuracy, can be applied to disease prevention in terms ofphenylketonuria gene mutation detection, carrier detection, genetic counseling and the like and can also be applied to disease treatment guidance.

The invention relates to a method for analyzing and detecting L-phenylalanine based on a liquid crystal sensor. The method comprises the following steps: (1) diluting a sample to be tested in a TBS buffer solution to prepare a solution to be tested; (2) adding an alkaline phosphatase solution into the solution to be tested to prepare an enzyme reaction solution after a reaction; and (3) dripping the enzyme reaction solution onto the liquid crystal sensor modified by a sodium lauryl phosphate solution, and performing observation by using a polarizing microscope. The method for analyzing and detecting the L-phenylalanine in the urine of a patient with phenylketonuria based on the liquid crystal sensor provided by the invention has the advantages of low detection limit, easiness to obtain thedetection instrument, simple, rapid and sensitive detection method, less reagent consumption, short sample processing time and the like, the problems that the existing detection method is complicatedand high in cost are solved.

The present invention provides compositions and methods of treating hyperphenylalaninemia (e.g., phenylketonuria) in a subject in need thereof comprising administering to the subject an effective amount of a phenylalanine dehydrogenase (PheDH) polypeptide. The present invention also provides pharmaceutical formulations comprising PheDH for lowering the phenylalanine concentration in the subject (e.g., in the intestines and / or blood).

A DNA chip for diagnosing the phenylketonuria (PKU) features that an array of 6X4 DNA probes with 6-30 amino connecting arms of T base for detecting the gene mutation of phenylalamine hyroxylase is immobilized in a predefined area on the surface of glass, silicon chip, film, or high-molecular material, so the gene mutations at the sites R111X, Y204C, R243Q, W326X, Y356X and R419P can be simultaneously detected.