The Molecular Bases of Phenylketonuria (PKU) in New South Wales, Australia: Mutation Profile and Correlation with Tetrahydrobiopterin (BH4) Responsiveness.

[phenylketonuria]

Phenylketonuria (PKU ) is an autosomal recessive inborn error of phenylalanine metabolism predominantly caused by mutations in the phenylalanine hydroxylase (PAH ) gene . Mutation screening was carried out in a large cohort of PKU patients from New South Wales , Australia . Pathogenic mutations were identified in 99 % of the alleles screened , with the two most common mutations (p .R 408 W and IVS 12 +1 G >A ) accounting for 30 .7 % of alleles . Most individuals were compound heterozygotes for previously reported mutations , but four novel mutations (c .163 +1 G >T , c .164 -2 A >G , c .461 A >T [p .Y 154 F ], and c .510 -1 G >A ) and a novel polymorphism (c .60 +62 C >T ) were also identified . A number of patients have been previously tested for their response to dietary supplementation of tetrahydrobiopterin (BH 4 ), the cofactor of PAH . Correlation between genotype and the responses revealed that although genotype is a major determinant of BH 4 responsiveness , patients with the same genotype may also show disparate responses to this treatment . A clinical and biochemical evaluation should be undertaken to determine the effectiveness of PKU treatment by supplementation of BH 4 .

Diseases
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Diseases presenting "large cohort" symptom

adrenal incidentaloma

adrenomyeloneuropathy

cadasil

child syndrome

congenital diaphragmatic hernia

cushing syndrome

cystinuria

erdheim-chester disease

esophageal adenocarcinoma

esophageal carcinoma

esophageal squamous cell carcinoma

fabry disease

familial mediterranean fever

inclusion body myositis

junctional epidermolysis bullosa

kabuki syndrome

krabbe disease

oligodontia

pendred syndrome

phenylketonuria

thoracic outlet syndrome

waldenström macroglobulinemia

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