BACKGROUND: Phenylalanine hydroxylase (PheOH) deficiency is inherited as an autosomal recessive trait. The associated hyperphenylalaninemia phenotype is highly variable, primarily due to great allelic heterogeneity in the PAH locus. The goal of our study was to assess the relationship between individual PAH locus mutations and biochemical and metabolic phenotypes in phenylketonuria (PKU) and mild hyperphenylalaninemia (MHP) patients. MATERIAL/METHODS: In this study, a total of 184 independent PAH chromosomes (92 unrelated patients with PKU and MHP residing in Lithuania) were investigated. All 13 exons of the PAH gene of all PKU probands tested were scanned for DNA sequence alterations by denaturing gradient gel electrophoresis (DGGE); mutations were identified by direct fluorescent automated sequencing or by restriction enzyme digestion analysis of the relevant exons. PAH genotype-based prediction of metabolic PhOH deficiency phenotype in PKU/MHP patients form Lithuania was estimated by the assigned value (AV) and functional hemizygosity methods. RESULTS: Our data provide evidence that a simple genotype-phenotype correlation does exist in most patients with PheOH deficiency: we observed a perfect match between the expected and observed phenotypes in 96% of the cases investigated. CONCLUSIONS: The results obtained confirm that methods of functional hemizygosity and AV sum are applicable for the estimation of the genotype-phenotype correlation in the investigated group of PKU/MHP patients.

Keywords: Phenylalanine - blood, Phenylalanine Hydroxylase - genetics, Phenylketonurias - blood, Phenylketonurias - enzymology, Phenylketonurias - genetics