Search

Abstract The neuronal ceroid lipofuscinosis type 2 (CLN2) is a heterogeneous group of neurodegenerative lysosomal storage disorders caused by autosomal recessive inheritance of two pathogenic variants in trans in the TPP1 gene. Classical late‐infantile CLN2 disease has a very well‐defined natural history. However, a small number of patients with TPP1 enzyme deficiency present a later onset or protracted disease course within this group there are phenotypic variants. Our work aimed to identify pathological variants in the TPP1 gene that conditioned the development of CLN2 disease in Ukrainian patients, to compare these variants with those found in patients from other European and non‐European regions, and to make genotype–phenotype associations for this disease. The phenotypes and genotypes of the 48 CLN2‐affected individuals belonging to 43 families were profiled through clinical data collection, enzyme analysis, and genotyping. In most patients, genotype and phenotype correlation are in keeping with the data of previous studies. The clinical signs of the disease in patients with new, previously undescribed variants, allowed us to augment existing data about genotype–phenotype correlations for CLN2 disease. The combination of genotype and clinical form of the disease demonstrated that predicting the type and clinical course of the disease based on genotype is very complicated. The data we obtained supplements existing information on genotype–phenotypic correlations in this rare disease, which, in turn, lays the foundation for a personalized approach to the management of this disease.

Summary. The article is devoted to a topical issue in pediatrics - hepatomegaly syndrome in a rare metabolic pathology - mucopolysaccharidosis type I. Goal. To study the possibilities of early diagnosis of hepatomegaly syndrome as one of the most important clinical manifestations of type I MPS and to determine early diagnostic criteria for the course of the disease. Materials and methods. Retrospective clinical study of 24 children with type I mucopolysaccharidosis who were diagnosed in Ukraine for 17 years (from 2004 to 2021). Patients underwent a complete comprehensive examination of the manifestations of the disease and determined the activity of the enzyme a-L-iduronidase in the lysosomes of leukocytes using a biochemical method, the study of the level of excretion of glycosaminoglycans in the urine. Results. Clinical symptoms and examination results in 24 children diagnosed with type I mucopolysaccharidosis in Ukraine were analyzed. The conducted comprehensive examination revealed a significant frequency of hepatomegaly syndrome among patients of this study. Its combination with other clinical symptoms. Hepatomegaly syndrome in children was found in 79 %, which was combined with other clinical symptoms of mucopolysaccharidosis, but never was the cause of the initial examination of the patient and the key symptom. Hepatomegaly was most often observed in the symptom complex with contractures and stiffness of the joints, curvature of the spine, lesions of the valvular apparatus of the heart and umbilical hernias. In contrast to the previously described studies, only 20% of hepatomegaly syndrome was combined with splenomegaly. Biochemical studies did not reveal liver dysfunction. There was also a direct relationship between the degree of hepatomegaly and the severity of glycosaminoglycan secretion. Conclusions. Liver enlargement syndrome in many childhood diseases, including orphan metabolic diseases, remains an underestimated diagnostic criterion. Detection of hepatomegaly syndrome can direct the diagnostic search of the practitioner to exclude hereditary metabolic disorders, including mucopolysaccharidosis. Early detection of such a complex and severe disease in children as mucopolysaccharidosis type I will allow to start treatment in time and prevent disability and early death.

Phenylketonuria (PKU) is hyperphenylalaninemia that develops due to a deficiency of the phenylalanine hydroxylase enzyme (PAH). Identification of variants in the PAH gene is necessary for verification of the diagnosis, choice of treatment tactics, detection of heterozygous carriers. The aim of the study was to analyze the effectiveness of identification of selected pathological variants in the PAH gene during the newborn screening program. This study relied on the results of the examination of 257 patients (138 boys and 119 girls) with hyperphenylalaninemia from different regions of Ukraine. Genotyping was performed on nine pathogenic variants in PAH gene: I65T, R261Q, G272*, R252W, R261*, R408W, IVS12 + 1G > A, Y414C, IVS10-11G > A. According to the results of the study, variants R408W (AF = 52.7%), R252W (AF = 3.5%) and Y414C (AF = 1.8%) were the most common. More than half of the examined patients (51.7%) had a compound genotype with a major variant of R408W in one allele. Approximately a quarter of the examined patients (26.8%) had the R408W/R408W genotype. In 12.1% of patients, the applied panel of variants of the РАН gene did not allow us to identify the pathogenic variant in any allele. We conclude that the selected panel allowed us to identify the presence of variants in 87.9% of patients with PKU. The panel of genetic testing in the PAH gene for the newborns that we used for the study allows accurate prediction of some phenotypes for therapy planning. But in-depth analysis of pathological gene variants may be necessary for unclear and difficult cases of the disease, and for genetic counseling of patients families.