Mutation screening versus gene scanning for genotyping phenylketonuria patients

Phenylketonuria (PKU) and its milder variant non-PKU hyperphenylalaninaemia (non-PKU HPA) (McKusick 261600) are recessively inherited disorders of phenylalanine metabolism (Scriver et al 1989). The biochemical abnormality causing elevated blood levels of phenylalanine in affected individuals is a complete or partial deficiency of hepatic phenylalanine hydroxylase (PAH), the enzyme catalysing the conversion of phenylalanine to tyrosine. Initial clinical studies and molecular studies based on RFLP haplotype analysis have indicated that PAH deficiency is a highly heterogeneous disease. To date, more than 60 different point mutations have been characterized in the PAH gene in various ethnic groups (Eisensmith and Woo 1992)