Genotype-phenotype correlation in phenylketonuria

Abstract

Introduction. Phenylketonuria is an inborn metabolism error with a high phenotypical variability, due in part to the large number of implicated genetical variants (over 1200 reported) but also due to other factors. Establishing a genotype=phenotype correlation, accessible today through molecular testing, is an important instrument for diagnostical accuracy, personalized therapy, better evaluation of the prognostic and an optimal genetical advice. Objective. The article aims to make an analyze of the most recent progress made in the effort of increasing the predictive value of genotyping in establishing the evolution and the severity of the disease. Material and method. For this review there were analyzed article from specialty journals indexed to Pubmed database, published mainly in the last 10 years. Results. Genotype-phenotype correlations can be established in most patients, but in approximative 10% of cases there are discordances between previously reported data and the result found in some studies. This mismatch results from the allelic interaction in compound heterozygous, not yet fully understood, from the existence of variants with unpredictable evolution and from other, non-genetical factors. Conclusions. The genotype-phenotype relationship is increasingly better understood. Molecular testing in phenylketonuria and phenotypical predictions based on the genotype, obtained by comparison with international databases, have clinical importance for the genetic advice given to the family and for the therapeutic decision, among other reasons.