The article provides information about the nature of atherogenic disorders in children. Much attention is devoted to the problem of the pathogenesis of atherosclerosis, the substantiation of its stress theory, whereas nosological essence is rejected. Atherosclerosis is considered as an evolutionary, genetically determined pathophysiological process that accompanies a person from conception to death, affecting the health quality and life expectancy. Attention is drawn to the issues of susceptibility to atherogenic disorders in children, which explanation allows us to solve the problems of their prevention and prophylaxis.

The review of the literature presents the clinical phenotype and genotype pathogenesis, renal prognosis of isolated and extra-renal manifestation form of hereditary nephrotic syndrome in children. The clinical and genetic features of hereditary steroid-sensitive and steroid-resistant nephrotic syndrome in children caused by mutations of genes encoding the main components of the slit diaphragm, glomerular basement membrane, structural and functional proteins of the podocyte are highlighted. Literature data demonstrate an unfavorable renal prognosis in children with hereditary steroid-resistant nephrotic syndrome with focal segmental glomerulosclerosis and diffuse mesangial sclerosis with clinical manifestation at the age of 0–17 years with progression to terminal renal failure at the age of 0.4–18 years. Renal replacement therapy with dialysis and kidney transplantation improves the prognosis, survival, and quality of life of children with hereditary nephrotic syndrome.

Idiopathic nephrotic syndrome is the most common glomerular disease in children, with a prevalence of 1.15–16.9 cases per 100,000 children per year worldwide. In some cases, nephrotic syndrome has a frequently relapsing course or dependence on steroid therapy is formed, which leads to the appointment of immunosuppressive therapy. So far, in clinical practice, there is no unambiguous approach among physicians to the management of patients with nephrotic syndrome, especially when it comes to the further choice of immunosuppressive therapy. Because of the serious side effects of long-term corticosteroid use, doctors prescribe steroid adjuvants to maintain remission and limit the cumulative effect of glucocorticosteroids. Among adjuvants, mycophenolate mofetil, with mycophenolic acid as the active ingredient, is believed to be the most preferred option due to fewer adverse events, acceptable tolerability and, at the same time, high efficacy. This article describes the advantages and features of the use of mycophenolic acid in clinical practice, provides data on pharmacodynamics and drug monitoring, and discusses issues of personalized medicine.

Marfan syndrome is an inherited connective tissue disease with autosomal dominant inheritance and pronounced phenotypic variability, which is highly likely to be caused by genetic modifiers. This review presents the molecular characterization of fibrillin-1, the protein product of the disease-associated FBN1 gene, the genotype-phenotype correlations studied to date, and the results of the search for possible genetic modifiers.

Allergy to cow’s milk proteins is the most common cause of allergic reactions in young children, with a significant impact on the quality of life of children and their families. The most significant biomarker of herbivore milk allergy is allergen-specific IgE (sIgE), which can be assessed both for the whole allergen (for example, cow’s milk (CM), mare’s milk, goat’s milk, etc.) and a specific molecule, included in their composition. This article focuses on the use of sIgE in infants with suspected cow’s milk protein allergy.

Intrauterine infections are serious diseases that largely determine the level of infant mortality. Newborns who have had intrauterine infections often have long-term consequences, leading to disability. One of the intrauterine infections is a congenital infection caused by the herpes simplex virus (neonatal herpes). Neonatal herpes occurs less frequently (1:2000 live births) than cytomegalovirus fection, but the clinical symptoms in this disease are characterized by multiorgan damage.

Purpose. To determine the role of immune factors in the development of congenital generalized HSV infection.

Material and methods. Twenty-two newborns with a severe form of congenital generalized infection caused by the herpes simplex virus infection were examined (group I). The control group consisted of 26 healthy newborns born to women with uncomplicated pregnancy and childbirth. Determination of the population and subpopulation composition of peripheral blood lymphocytes and monocytes, the level of expression of activation markers, T-regulatory cells (Treg) was carried out by laser fl w cytometry using reagents from Immunotex (France), Caltag (USA), HyCultbiotechnology (Netherlands): FITC (fl           escein isothiocyanate) — labeled CD3+, CD4+, CD8+, CD 16+, CD19+, CD282+ and PE (phycoerythrin)-labeled CD95+, CD25+, CD14+. Determination of the number of lymphocytes that have entered apoptosis using a diagnostic kit including Annexin-V, labeled with FITC and propidium iodide (PI), (Caltag, USA). The concentration of IFN-γ, IFN-α, IL-12 in the blood serum of newborns was determined by ELISA using BenderMedsistems test systems.

Results. The development of a congenital generalized infection caused by the herpes simplex virus is associated with a lack of IFN-α, IFN-γ, IL-12 production, a decrease in the number of monocytes expressing TLR-2, a decrease in the relative number of CD8+, CD16+ lymphocytes, CD25+ activation markers, on the surface of NK cells, in combination with an increase in CD16 + CD95 +, AnnexinV + PI +, the number of Tregs.

Conclusion. The results of the work indicate suppression of the early stages of the innate immune response, impaired effector function of immunocompetent cells, apoptosis processes

Purpose. To study the patient’s characteristics and hospital outcomes in subgroups depending on the PNCAS scale score.

Material and methods. The cohort study included data from 604 trips of the transport team to newborns hospitalized in medical organizations of the Sverdlovsk region from August 1, 2017, to December 31, 2018. Median birth weight [IQR] 2515 [1600; 3275] grams, median gestational age [IQR] 36 [32; 38] weeks. The total sample was divided into subgroups depending on the assessment of the score, followed by a comparison of characteristics and outcomes in these subgroups.

Results. There are significant differences in the structure of birth weight and gestational age, as the PNCAS score increases, there is a significant increase in the proportion of patients weighing less than 1000 grams and a decrease in the proportion of patients weighing 2500–3499 grams. The largest proportion of extremely premature newborns was observed in 6–8 points and 9–14 points subgroups, 30.16% and 24.00%, respectively. Assessment of the intensive care showed an increase in the proportion of patients requiring HFOV, dopamine and epinephrine infusion while increasing PNCAS score. Analysis of the outcomes showed a significant increase of mortality while increasing PNCAS score, 0.76% [0.02; 4.18] in the 0–2 points subgroup and 42.86% [21.82; 65.98] in the 9–14 points subgroup. There is also an increase in the proportion of patients who have formed severe IVH, 0.00% [0.00; 2.78] in the 0–2 points subgroup and 19.05% [5.45; 41.91] in the 9–14 points subgroup. A similar pattern is observed in the frequency of late onset sepsis.

Conclusion. The PNCAS scale we studied demonstrates a reliable division of patients by severity and predicts the outcomes of the hospital stage of treatment.

Volatility of certain bronchial asthma (BA) phenotype markers is not enough investigated during maturation of pediatric patients. Material and methods. One hundred thirty-one patients with non-severe BA were included; by the age on inclusion date subgroups of “Children” (62 patients aged 6 to 11 years) and “Adolescents” (69 patients aged 12–17 years) were allocated. Every 6 months patients were examined, fulfi   d asthma control questionnaires, performed spirometry with salbutamol test, provided hematology results with absolute eosinophil count and height and weight data. Exacerbation and hospitalization numbers, BA severity and controller treatment step were considered. Acquired data were archived; patients’ management was driven by real clinical practice algorithms.

Results. Ninety-three patients included (71%) completed at least decade observation. Adolescents and young adults had body mass index higher than 90th percentile by age more often than younger children; some patients had normalized their body mass during observation. BMI and ACT results had moderate reverse correlation (r=–0.64). Eosinophil counts more than 300 cells per microliter conserved longer in older patients: duration median and [Q1; Q3] for “Adolescents” were 11,7 [9,6; 15,3] months and 9.3 [4.8; 11.1] months for “Children” subgroup, difference was significant (р=0.043). Most lung functional parameters were in age normal range. Rare cases of functional obstruction were not stable and did not differ in duration between “Children” 7.3 [6.2; 8.8] months and “Adolescents” 8.4 [6.5; 10.4] months.

Conclusion. Phenotype markers of future BA exacerbation risk are quite volatile in pediatric patients and young adults. We recommend repeated evaluation of such markers every 12–18 month of observation to decide on asthma controller change. Simultaneous detection of several markers was quite often but did not lead to more severe asthma course in most patients. Longer duration of elevated BMI or peripheral blood eosinophils were typical for patients with more often BA exacerbations.

The impact of gut microbiota on the development of various diseases is of great interest to researchers. However, data on the taxonomic diversity of the intestinal microbiota in chronic liver diseases in children are lacking.

Purpose. To study the taxonomic diversity of the fecal microbiota in children with chronic liver diseases in comparison with healthy patients.

Material and methods. A metagenomic analysis of the intestinal microbiota of 24 children with chronic liver diseases (mean age 10.3 ± 4.7 years) was carried out with the isolation of the target fragment of the 16S rRNA gene. The group included 18 children with autoimmune liver diseases and 6 children with non-autoimmune liver diseases. The comparison group consisted of fecal samples of 34 apparently healthy children.

Results. The conducted study revealed 684 types of microorganisms in the studied samples of patients’ feces. An analysis of the conducted studies showed that fecal samples of healthy children and patients with chronic liver diseases differ in bacterial diversity. The dominant taxa in healthy children were Neisseria flavescens, in patients with chronic liver diseases, the dominant taxa were Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis. At the same time, Bifidobacterium longum, Bifidobacterium adolescentis, Blautia massiliensis in fecal samples of patients with chronic liver diseases was 8 times as high.

Conclusion. Studies have shown differences in the composition of the intestinal microbiota in healthy children and children with chronic liver diseases.

Currently, it has been established that obesity in children with bronchial asthma leads to a more severe course of the disease, a worse quality of life, and a reduced response to treatment.

Purpose. To study the incidence and risk factors of simple obesity in children with bronchial asthma. The aim of the study was to study the incidence and risk factors of simple obesity in children with bronchial asthma.

Material and methods. The study included 484 patients aged 7 to 14 years: the main group consisted of 237 patients with atopic bronchial asthma, the comparison group consisted of 247 children without a diagnosis of bronchial asthma.

Results. Patients of the main group were obese more often (18.9%) than children of the comparison group (11.3%, p=0.019). During 5 years of bronchial asthma disease, a tendency (p=0.087) was revealed to increase the SDS body mass index indicator in the dynamics of the disease (from 0.32 to 0.45) and the number of patients with III and IV degrees of obesity (from 10.5% to 42.8%, p=0.025). In children of the main group with normal SDS body mass index before the diagnosis of bronchial asthma 5 years after the onset of the disease, in 8.5% of cases there was obesity (p<0.001) and in 23.9% — excess body weight (p<0.001), in children with initial excess body weight, obesity was diagnosed in 28.6% of cases (p=0.048), and among children who were obese at the time of bronchial asthma, 26.3% had an increase in its severity (p=0.023). In patients with bronchial asthma and obesity, according to the bioimpedance analysis findings, a pronounced imbalance between energy intake and its consumption was revealed, and according to the nutrition assessment data — an unbalanced diet, a violation of the diet and a sedentary lifestyle.

Conclusion. Simple obesity occurs in 18.9% of school-age children with atopic bronchial asthma, and over the course of 5 years of the disease, the number of patients with obesity increases and its severity progresses. Therefore training of patients and their parents, correction of nutrition and increasing the volume of physical activity are an important component of treatment.

Congenital methemoglobinemia, especially caused by pathological hemoglobin M, is an extremely rare cause of cyanosis in newborns. The time to onset and severity of clinical manifestations in hemoglobin M disease depends on which globin chain the mutation occurred in.

Purpose. To present the case of congenital methemoglobinemia associated with hemoglobin M disease, not recognized in the neonatal period, to summarize the data on diagnosis, therapy, and prognosis for this pathology.

Clinical case. In a full-term child without organ pathology, the development of diffuse cyanosis in the early neonatal period, a decrease in pSO2 of 70%, resistant to oxygen therapy, and increasing anemia were noted. The level of methemoglobin is up to a maximum of 17%. A decrease in the level of methemoglobin to 5.7% and stabilization of pSO2 >90% were obtained after two transfusions of erythrocyte suspension. No pathological forms of hemoglobin were detected during electrophoresis on the 5th day of life. Repeated electrophoresis at the age of 5 months revealed a pathological hemoglobin fraction of 8.9% corresponding to hemoglobin M Iwate. During the first year of observation, the growth and development of the child corresponds to the age norm. Stable acrocyanosis. Methemoglobin in the blood remains at the level of 8.7–8.9% without specific therapy for the last 6 months.

Conclusion. The diagnosis of congenital methemoglobinemia due to the presence of defective hemoglobin M (M-hemoglobinopathy) was established basing on the high persistent level of methemoglobin (9–12%) and hemoglobin electrophoresis identified an abnormal hemoglobin M (HbM Iwate) variant.

Barakat Syndrome (MIM#146255) is a rare autosomal dominant disease caused by GATA3 gene mutation and manifested by hypoparathyroidism (H), sensorineural deafness (D), and renal disease (R). HDR syndrome characterized by high clinical variability and prognosis. The exact prevalence of this disease is unknown, 180 cases are reported in the literature. Two clinical cases are presented. De novo heterozygous mutation in the GATA3 gene was detected in both patients. Our observations demonstrate variability of clinical phenotypes and poor prognosis in patients with Barakat Syndrome. The syndrome should be suspected in cases of early high-grade deafness and kidney disease presentation for the purpose of early diagnosis and appropriate therapy including the prevention of CKD progression.

Nephrotic syndrome is one of the most common glomerulopathies in children, accompanied by a high risk of thrombosis due to hypoalbuminemia, hypovolemia, hyperlipidemia, hyperfibrinogenemia, and antithrombin III deficiency. The article describes a clinical case of iliofemoral thrombosis in a 16-year-old boy with recurrent nephrotic syndrome and primary thrombophilia (heterozygote F5 — Leiden mutation) was diagnosed. The presented clinical observation indicates the multifactorial origin of thrombotic complications in nephrotic syndrome, caused by a combination of an imbalance between the proand anticoagulant components of the blood coagulation system and individual risk factors (severity of proteinuria, hypoalbuminemia, comorbidity, hereditary thrombophilia), and therefore further study is needed to determine the tactics of prevention and treatment.

The term «homocystinuria» combines a number of genetically determined nosological forms caused by defects of the metabolism of sulfur-containing amino acids (methionine, homocysteine), cobalamin and folate. The group of these diseases includes «classical» homocystinuria caused by insufficiency of cystathionine beta-synthase and forms associated with defects in methionine remethylation processes. More information is given about one of these forms — homocystinuria and megaloblastic anemia, type cblG, caused by MTR gene mutations. The results of observation of a child with this disease are presented. The clinical status includes: intellectual disability, autistic behavioral traits, stereotypes, nystagmus, visual impairment, macrocytic anemia, epilepsy in remission. Effective treatment requires the use of medications not registered in the Russian Federation — betaine and hydroxocobalamin.