Heterogeneity of mutations in Bulgarian phenylketonuria haplotype 1 and 4 alleles

A study of Bulgarian patients with classical PKU demonstrated that haplotypes 1 and 4 carry a significant number of rare molecular defects resulting from independent mutational events. Differences in mutations associated with these common haplotypes exist even between populations which share a common major PKU mutation. Some amino acid substitutions, previously reported to lead to mild phenylalanine hydroxylase deficiency, were detected in the present study in compound heterozygotes with severe PKU. These findings preclude carrier testing and hyperphenylalaninemia typing by genomic analysis at least in the heterogeneous Bulgarian population.