Phenylketonuria (PKU) is an inborn error of metabolism that results from a deficiency of phenylalanine hydroxylase (PAH). We characterized the PAH mutations of 79 independent Korean patients with PKU or hyperphenylalaninemia. PAH nucleotide sequence analysis revealed 39 different mutations, including ten novel mutations. The novel mutations consisted of nine missense mutations (P69S, G103S, N207D, T278S, P281A, L293M, G332V, S391I, and A447P) and a novel splice site variant (IVS10-3C>G). R243Q, IVS4-1G>A, and E6-96A>G were the most prevalent mutations, as they accounted for 32% of the total mutant alleles in this study. Although some common characteristics of allele frequency and distribution were identified among oriental populations, several distinctive characteristics were revealed in Korean patients. Although the R413P allele is the most prevalent form (30.5%) in Japanese, we detected it in only five chromosomes from 158 independent chromosomes (3.2%). The A259T allele, which has not yet been found in oriental populations, was frequently found in this study. We also observed that tetrahydrobiopterin (BH4) responsiveness was associated with specific genotypes (R53H, R241C, and R408Q), suggesting there are some correlations between phenotype and genotype.
- Phenylalanine hydroxylase