Background There is a vast number of screening studies described in the literature from the beginning of the twenty-first century to the present day. Many of these studies are related to the estimation of Fabry disease (FD) morbidity among patients from high-risk groups, including adult patients with hypertrophic cardiomyopathy (HCM) and left ventricular hypertrophy (LVH). These studies show diverse detection frequencies (0–12%) depending on the methodology. Our study is the only example of large-scale selective FD screening based on the implementation of next-generation sequencing technology (NGS) as a first-level test to estimate FD morbidity in the Russian population over 18 years of age burdened with HCM. Methods The study included 1009 patients (578 males and 431 females), with a median age of 50 years, who were diagnosed with HCM according to current clinical guidelines. In the first stage of screening, all patients underwent molecular genetic testing (NGS method) of target regions. These regions included the coding sequences of 17 genes and mutations that can lead to the development of HCM. Lysosomal globotriaosylsphingosine (lyso-Gb3) concentrations and α-galactosidase A (α-gal A) enzyme activity were measured in the second stage of screening to reveal pathogenic or likely pathogenic variants in the GLA gene. Results We revealed 8 (0.8%) patients (3 (37.5%) males and 5 (62.5%) females) with an average age of 59 ± 13.3 years who had pathogenic, likely pathogenic variants and variants of uncertain significance (VUS) in the GLA gene (NM_000169.2) as a result of selective screening of 1009 Russian patients with HCM. FD was confirmed via biochemical tests in a male with the pathogenic variant c.902G > A, p.R301Q as well as in two females with likely pathogenic variants c.897C > A, p.D299E and c.1287_1288dup, p.*430Fext*?. These tests showed reduced enzymatic activity and increased substrate concentration. However, a female with the pathogenic variant c.416A > G, p.N139S and with normal enzymatic activity only had increased substrate concentrations. The revealed nucleotide variants and high values of biochemical indicators (lyso-Gb3) in these 4 patients allowed us to estimate the FD diagnosis among 1009 Russian patients with HCM. Mild extracardiac manifestations were observed in these four patients; however, both biochemical values within the reference range in females with the c.971T > G, p.L324W (VUS) variant. α-gal A activity and lyso-Gb3 concentrations were also within the normal range in two males with hemizygous variants, c.546T > C, p.D182D and c.640-794_640-791del (we regarded them as VUS), and in one female with the c.427G > A, p.A143T variant (with conflicting interpretations of pathogenicity). Conclusion The prevalence rate of FD among 1,009 adult Russian patients with HCM was 0.4%. We recommend FD screening among adult patients of both sexes with HCM and an undefined genetic cause via NGS method with subsequent analysis of α-gal A activity and lyso-Gb3 concentration in patients with pathogenic, likely pathogenic variants, and VUS. This strategy identifies patients with an atypical form of FD that is characterized by high residual activity of α-gal A, low concentrations of lyso-Gb3, and minor extracardiac manifestations.

The few foreign papers of the last decade have shown the relationship of various pathogenic variants of the ELAC2 gene to heterogeneous phenotypic manifestations, for which the unfavorable prognosis is common, caused by severe cardiomyopathy in the first year of life. The article presents the first clinical observation of a rare variant of the hypertrophic phenotype cardiomyopathy with a fatal outcome in the first year of life, and variants c.887T>C, p.L296P and c.1979A>T, p.K660I of the ELAC2 gene in Russia.The purpose of the work is to present clinical observation of a child with an early manifestation of a hypertrophic phenotype of cardiomyopathy caused by pathogenic variants of the ELAC2 gene.

Aim of the study: to determine the features of the formation of psychophysiological and cognitive functions in 6-17 year children using a comprehensive and screening software of the original package of the complex “Psychomat”. Materials and methods. A screening examination of 184 apparently healthy 6-17 year schoolchildren was carried out using a complex of psychophysiological tests and original methods for studying higher mental functions (24 tests, 66 parameters). To verify the screening program, a comprehensive examination of 60 apparently healthy schoolchildren of the same age was carried out. Results. The patterns of formation of cognitive and psychophysiological functions in 6-17 year children have been established. No gender differences were found in the analysis of cognitive and psychophysiological functions in children. Significant differences in the rate of formation of psychophysiological functions have been identified in children of primary school age (8-10 years) and are associated mainly with the speed of response and coordination. As the age of children increases, test parameters reflecting the characteristics of perception, memory, attention, analytical and synthetic processes also undergo changes: both the total and average time for completing tasks and the number of errors decrease, and the pace of execution increases. Conclusion. The original software package «Psychomat» allows using comprehensive and screening assessment of both psychophysiological and cognitive functions in 6-17 year children. The screening software as the sensitive method for detecting violations of psychophysiological and cognitive functions in the conditions of a mass examination of children can be used as a test system.

A unique clinical case of a combination of malformations of the anterior abdominal wall (omphalocele of large size) and malformation of the lymphatic system (congenital chyloperitoneum) is presented. Each of these defects can lead to a fatal outcome, and the combination of them has greatly increased the risk of developing an unfavourable outcome. The use of immunosuppressive therapy with Sirolimus used for the first time during the newborn period made it possible to completely stop the chyloperitoneum. This clinical example shows that in the treatment of surgical patients with multiple congenital malformations, a multidisciplinary approach and observation is necessary for timely response to the patient’s condition.