IN-VIVO DISPOSAL OF PHENYLALANINE IN PHENYLKETONURIA - A STUDY OF 2 SIBLINGS

Mutation at the phenylalanine hydroxylase (PAH) locus is a cause of hy perphenylalaninaemia. Genotype-phenotype correlation relative to the p redicted PAH activity may differ at the metabolite level and at the IQ level in untreated phenylketonuria. Discordant metabolic phenotypes h ave been noted in siblings; influences on transport and metabolism of phenylalanine determining homeostasis may account for differing metabo lic phenotypes. We report two siblings of different sex and identical genotype at the PAH locus who demonstrate a difference in phenylalanin e disposal. A stable isotope infusion of [H-2(5)]phenylalanine was use d to measure protein turnover, phenylalanine hydroxylation and excreti on of phenylalanine transamination metabolites. The siblings were obse rved to have identical hydroxylation rates under the experimental cond itions of the study while manifesting differences in renal excretion r ates of phenylalanine transamination metabolites and protein accretion .