Results of genotyping program of PKU and HPA patients

Introduction: Phenylketonuria (PKU) - a hereditary metabolic disease that arises from mutations in the PAH gene, the part of the program of neonatal screening in the Russian Federation. Patients with PKU need to follow a diet for life, limiting the intake of natural protein in the body to prevent the development of clinical manifestations of the disease, the main of which is a delay in mental development. Data on the genotype of patients with PKU make it possible to predict their sensitivity to the cofactor therapy, which allows to expand significantly the diet and improve the quality of life. Patients and methods: The study was conducted between December 2016 and January 2018 at the DNA Diagnostics Laboratory of the Federal State Budgetary Institution «Research Centre for Medical Genetics». Material from 1254 unrelated probands was examined for the presence of 25 frequent mutations of the PAH gene. Results: Pathogenic variants are revealed on 86,3% of the investigated chromosomes. In 75.3% of patients, the diagnosis of «phenylketonuria» caused by mutations in the PAH gene was confirmed by molecular genetic methods. Only one pathogenic variant was found in 22.1% of probands, 2.6% did not reveal pathogenic variants of the PAH gene. The allelic frequencies of 25 frequent mutations of the PAH gene are determined. Regional differences in the prevalence of the R408W mutation, as well as the heavy and soft mutations of the PAH gene, are revealed. According to the results of the study, 56.9% of patients are «non-responders» to BH4 therapy, 21.8% - are potential «responders». Discussion: Using the Hardy-Weinberg ratio, we can calculate the total allelic frequency of 25 mutations and the frequency of R408W, calculate the number of patients with mutations in the BH4 synthesis and metabolism genes and the number of R408W homozygous patients not included in the genotyping program.

фенилаланингидроксилаза, тетрагидробиоптерин, сапроптерин, phenylalanine hydroxylase, tetrahydrobiopterin, sapropterin

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