MUTATIONAL SPECTRUM OF PHENYLALANINE-HYDROXYLASE DEFICIENCY IN SICILY- IMPLICATIONS FOR DIAGNOSIS OF HYPERPHENYL-ALANINEMIA IN SOUTHERN EUROPE

Hyperphenylalaninemia due to a deficiency of hepatic phenylalanine hyd roxylase (PAH) is the most common inborn error of amino acid metabolis m. Clinically, the disorder is highly heterogeneous, spanning from non phenylketonuria hyperphenylalaninemia to classical phenylketonuria. On ly little is known about the molecular defects underlying hyperphenyla laninemia in Southern Europe. In this study, we conducted a systematic analysis of 53 patients from the Sicilian population. Each patient in cluded in the study had persistently elevated blood levels of phenylal anine and met the differential criteria for PAH deficiency. Genomic DN A was analysed by scanning all PAH-coding exons for mutations by PCR i n combination with denaturing gradient gel electrophoresis (DGGE). 52 patients were completely genotyped. A spectrum of 40 different mutatio ns was established including 17 novel PAH mutations. Our results expla in the clinical heterogeneity of hyperphenylalaninemia in Southern Eur ope, and form the basis for the establishment of phenotype - genotype correlations in Sicily and surrounding countries.