The correlation of genotype and phenotype in Portuguese hyperphenylalaninemic patients

To understand the basis for the clinical heterogeneity of phenylalanine hyd roxylase deficiency among Portuguese hyperphenylalaninemic patients, genoty pe-phenotype correlations were established. A group of 61 patients was comp letely genotyped, leading to the identification of 20 different mutant alle les in 36 different genotypic combinations, including a mutant allele not r eported previously. The severity of those mutations found within this hyper phenylalaninemic population, which have not been previously expressed in vi tro, were assessed. The results obtained by the present study exhibit a str ong correlation between the predicted residual enzyme activity, as deduced from the genotype of the patients, and the biochemical phenotype represente d by the diagnostic parameters (phenylalanine levels before the beginning o f treatment and the dietary phenylalanine tolerance). It was observed that only a judicious follow-up and compliance with the appropriate diet permits the correct assessment of the clinical phenotype of the patients. Addition ally, based upon the correlation observed between genotypes and diagnostic parameters, it was possible to predict the potential residual enzyme activi ty of those mutations (identified in our patients) which have not yet been studied in vitro. (C) 2000 Academic Press.