Tetrahydrobiopterin-deficient hyperphenylalaninemia in the Chinese

Background: Hyperphenylalaninemia (HPA) may be caused by either a deficiency in phenylalanine-4-hydroxylase or in tetrahydrobiopterin (BH4), the essential cofactor required for the hydroxylation of aromatic amino acids. The most common forms of BH4 deficiency are 6-pyruvoyl-tetrahydropterin synthase (PTPS) deficiency (MIM 261640) and dihydropteridine reductase (DHPR) deficiency (MIM 261630), which require a different treatment from classical HPA. Results: Approximately 86% of BH4-deficient HPA in the Chinese population was found to be caused by PTPS deficiency. Eleven missense (73C→G, 120T→G, 155A→G, 166G→A, 200C→T, 209T→A, 226C→T, 259C→T, 286G→A, 317C→T, 430G→C), one splicing (IVS3+1G→A) and two deletion mutations (116-119delTGTT, 169-171delGTG) were identified in 37 unrelated PTPS-deficient Chinese families. Among these, 155A→G, 259C→T and 286G→A mutation accounted for about 80% of the mutant alleles. The 155A→G and 286G→A mutations were found to be the common mutation in southern and northern Chinese, respectively. Only two Chinese DHPR-deficient families were detected among about 300 Chinese hyperphenylalaninemia cases. A single base transition 508G→A on the DHPR cDNA was identified in two consanguineous DHPR-deficient siblings. A reduced level of DHPR mRNA expression was found in the other DHPR-deficient patient, which suggested that the mutation might lie in the regulatory region of the DHPR gene. Conclusions: The BH4-deficient HPA was estimated to make up around 30% of the Chinese population in Taiwan suffering from HPA, which is much higher than in Caucasian populations (1.5–2% of HPA).