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
Validation

Diseases presenting "common mutations" symptom

alexander disease

alpha-thalassemia

congenital adrenal hyperplasia

dentinogenesis imperfecta

familial mediterranean fever

gm1 gangliosidosis

homocystinuria without methylmalonic aciduria

krabbe disease

lamellar ichthyosis

phenylketonuria

primary hyperoxaluria type 1

x-linked adrenoleukodystrophy

zellweger syndrome

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