Biochemical Phenotype and Its Relationship with Genotype in Hyperphenylalaninemia Heterozygotes

The molecular detection of heterozygotes for hyperphenylalaninemia is difficult 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 been 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 in 93 parents of hyperphenylalaninemia patients allows the study of the biochemical expression of the different mutant alleles. Molecular study was performed by SSCP and DGGE analyses of PAH genes, and plasma amino acid analysis 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 biochemical phenotype (Phe/Tyr, Phe2/Tyr) as an expression of the residual enzymatic activity. The study adds further information about the prevalent Mediterranean allele mutations.