Biochemical phenotype and its relationship with genotype in hyperphenylalaninemia heterozygotes

The molecular detection of heterozygotes for hyperphenylalaninemia is diffi cult due to the large number of mutations in the PAH gene. For this reason, various indexes that measure plasma concentrations of phenylalanine (Phe) and tyrosine (Tyr), as an expression of Phe metabolizing capacity, have bee n used for the detection of carriers for mutations in the PAH gene. In this Study, we contrast the biochemical and the molecular data in order to know if this is an accurate method. Familial genetic analysis of the PAH gene i n 93 parents of hyperphenylalaninemia patients allows the study of the bioc hemical expression of the different mutant alleles. Molecular study was per formed by SSCP and DGGE analyses of PAH genes, and plasma amino acid analys is by ion-exchange chromatography. Then the biochemical and molecular data were compared by the Student t test. The results found show a relationship between the severity of PKU/HPA mutations in the PAH gene and their biochem ical phenotype (Phe/Tyr, Phe(2)/Tyr) as an expression of the residual enzym atic activity. The study adds further information about the prevalent Medit erranean allele mutations. (C) 1999 Academic Press.