Clinical and Genetic Characteristics of Phenylketonuria in Ryazan Region

Aim. This investigation seeks to determine the incidence of phenylketonuria in the Ryazan region, assess the spectrum of mutations in the PAH gene (phenylalanine hydroxylase), investigate the interrelationship between the disease's clinical course, the phenylalanine blood level, and the patient's genotype. Materials and Methods. The incidence of phenylketonuria was studied based on the data of massive neonatal screening for the period from 2000 to 2019. Molecular genetic examination of mutations was conducted in 39 patients using the allele-specific multiplex ligation method. The interrelationship between the phenylalanine blood level on the fifth day of life and retest, the disease's clinical course, and the patient's genotype was assessed according to the medical record data of 33 patients under dispensary observation in a medico-genetic clinic. The patients were divided into two groups. The first group (n=21) had two «severe» mutations (residual activity of phenylalanine hydroxylase <10%). The second group (n=12) had one «severe» and one «mild» mutation (the residual activity of the enzyme >10%). Results. The incidence of phenylketonuria in the Ryazan region was one in 5054 newborns, exceeding the Russian Federation's average parameters. Eighteen mutations were discovered in the PAH gene. The most frequent was the R408W mutation (56.4% alleles). The second most frequent mutations were the IVS10-11G>A (6.4%) and P281L (5.1%). The R158Q and Y418C mutations occurred with a frequency of 4.1% and Е280К mutation of 2.7%. All the rest of the mutations occurred as single cases. Investigation of the interrelationship between the phenylalanine blood level, the disease's clinical course, and the patient's genotype revealed a reliably higher content of amino acid in the first group on retest (32.1±1.7 mg/% vs. 17.7±1.5 mg/% in the second group, р<0.001) and predomination of more severe forms of phenylketonuria (90.5% vs. 41.7%, respectively, р<0.001). Disorders in neuropsychic and speech development were present in 28.6% of patients in the first group but were absent in the second group. Conclusion. By conducting the study, the incidence of phenylketonuria was determined in the Ryazan region. The spectrum of mutations in the PAH gene was defined. The interrelationship between the disease's clinical portrait, the phenylalanine blood level, and the patient's PAH genotype was revealed.