Clinical and Genetic Characteristics of Phenylketonuria in Ryazan Region

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Abstract

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.

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About the authors

Grigorii I. Yakubovskii

Ryazan State Medical University; Ryazan Regional Perinatal Center

Author for correspondence.
Email: yakubgreg@mail.ru
ORCID iD: 0000-0003-1266-0818
SPIN-code: 5726-5132
ResearcherId: AAK-6684-2020

MD, PhD, Associate Professor of the Histology, Pathological Anatomy and Medical Genetics Department, Ryazan State Medical University; Head of Medical and Genetic Consultation, Regional Clinical Perinatal Center

Russian Federation, Ryazan; Ryazan

Olga B. Serebriakova

Ryazan Regional Perinatal Center

Email: 3871117@mail.ru
ORCID iD: 0000-0002-5591-856X
SPIN-code: 2821-1790
ResearcherId: AAK-9841-2020

Doctor Laboratory Geneticist of Medical and Genetic Consultation, Regional Clinical Perinatal Center

Russian Federation, Ryazan

Alina G. Yakubovskaya

Ryazan State Medical University

Email: info@eco-vector.com
ORCID iD: 0000-0002-6994-1947
SPIN-code: 8685-0410
ResearcherId: AAM-8936-2020

MD, PhD, Associate Professor of the Polyclinic Therapy and Preventive Medicine Department, Ryazan State Medical University

Russian Federation, Ryazan

Nadezhda V. Ruban

Ryazan Regional Perinatal Center

Email: info@eco-vector.com
ORCID iD: 0000-0002-1565-3624
SPIN-code: 3212-0101
ResearcherId: AAK-8816-2020

Doctor of Clinical Laboratory Diagnostics of Medical and Genetic Consultation, Regional Clinical Perinatal Center

Russian Federation, Ryazan

Angelina A. Lyakhovets

Ryazan State Medical University

Email: info@eco-vector.com
ORCID iD: 0000-0001-7281-2612
SPIN-code: 6399-8884

Student, Ryazan State Medical University

Russian Federation, Ryazan

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Copyright (c) 2021 Iakubovskii G., Serebriakova O.



Свидетельство о регистрации СМИ ПИ № ФС77-76803 от 24 сентября 2019 года выдано Федеральной службой по надзору в сфере связи, информационных технологий и массовых коммуникаций (Роскомнадзор).


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