Generalized data on the role of medical genetics in the development of pediatric nephrology are given on the basis of the authors’ observations and modern literature. It is shown that the introduction of genetic researches into the practice of a pediatric nephrologist can change the view of the etiology of many diseases, decipher the essence of a number of nephropathies, the cause of which was unclear, and reduce the number of idiopathic diseases. This is particularly important for the determination of therapeutic tactics and the emergence of new pathogenic agents that can improve prognosis and quality of life in patients in a number of genetic diseases. Particular attention is drawn to hereditary nephropathy accompanied by hematuria and particularly to Alport syndrome characterized by a progressive course. The development of genetics and clinical introduction of its advances have recently led to the identification of a new nosological entity — hereditary C3 glomerulonephritis as a result of CFHR5 gene mutation. Thanks to the development of genetic technologies, new genetic kidney diseases are certain to be disclosed in the next future. 

It is widely known that mitochondrial DNA mutations may have a substantial impact on the development and course of different multisystem diseases. However, the mitochondrial genome is highly variable; even in the absence of pathological mutations, it carries important individual traits. Some mitochondrial DNA polymorphisms have been fixed by inheritance for thousands of years; they have phylogenetically developed as mankind has been settling in new places. Up to date, these polymorphisms are arranged into the socalled haplogroups. The purpose of this review is to analyze the recent literature on the relationship of the inheritance pattern of the mitochondrial genome (i.e. haplogroups) to phenotypic features. The structure of mitochondrial DNA can phenotypically manifest itself as the body’s physiological properties, predisposition to one or other type of a sport load, and longevity. On the other hand, the individual mitochondrial DNA structure can influence the risk of developing metabolic disturbances, brain disorders, immune system diseases, mental disorders, inflammation, or sepsis. Many investigations deal with the impact of mitochondrial DNA characteristics on predisposition to cancer and the course of this disease. The influence of mitochondrial DNA characteristics on susceptibility to different treatment modalities, such as transplantation, antiretroviral therapy, etc., deserves special attention. This review not only identifies the most interesting recent investigations, but also considers up-to-date methodological approaches to studying mitochondrial haplogroups. Due to the global disembodied results of an analysis of haplogroups today, it is very important to highlight ongoing studies as widely as possible. 

The common cause of mitochondrial diseases is hereditary defects in mitochondrial respiratory chain complex I, which account for about 30% of the cases of mitochondrial diseases in children. Complex I is the largest and most complicated enzyme complex of the respiratory electron chain. The function of Complex I is controlled by both nuclear and mitochondrial genomes and it seems to be determined by at least 300 genes. Complex I is comprised of 45 subunits: 7 of them are encoded by mitochondrial DNA, the others are by nuclear DNA. Besides, there are additional factors that are located outside Complex I, but determine its stability and activity. The paper analyzes the clinical forms of Complex I deficiency-induced diseases; the most common of them is Leigh syndrome. The diseases are generally characterized by an early onset, severe involvement of the nervous, muscular, and cardiovascular systems. If the treatment is ineffective, it is particularly important to identify a gene mutation to verify the diagnosis, as well as antenatal diagnosis. 

Hypertrophic cardiomyopathy is the most common inherited disease of the myocardium. The causes of the disease are heterogeneous; its primary form results from mutations in the genes encoding cardiac sarcomeric proteins; its secondary (metabolic and syndromic) forms develop due to mutations in the genes encoding non-sarcomeric proteins. Glycogenosis is the most common cause of the metabolic ones of hypertrophic cardiomyopathy. Danon’s disease (lysosome-associated membrane protein 2 (LAMP2-cardiomyopathy) is a form of glycogenosis and it is characterized by a typical triad: hypertrophic cardiomyopathy, mental retardation, and skeletal myopathy. The disease occurs with mutations in the LAMP2 gene; X-linked dominant inheritance. LAMP2-cardiomyopathy does not virtually differ in its clinical manifestations from the severe form of hypertrophic cardiomyopathy, which results from mutations in the sarcomeric protein genes. The disease is characterized by a poor progressive course with the high probability of causing sudden death or with the progression of severe heart failure. Implantation of a cardioverter defibrillator is a main method to prevent sudden cardiac death. 

The literature review summarizes current information on the causes of and mechanisms for the development of anemia in children with chronic kidney disease. It demonstrates the relationship between the severity of anemia and iron metabolism, hepcidin, erythropoietin deficiency, and changes in the levels of hypoxia-inducible factor 1 (HIF-1) and HIF-2 in different stages of chronic kidney disease in children. There are data on the value of HIF-1α in stimulating erythropoiesis in the early stages of chronic kidney disease. The studies have shown a reduction in HIF-1α in the later stages of this disease. 

The article reviews studies dealing with the use of the polypeptide nootropic and neurometabolic stimulant cortexin in the multimodal rehabilitation of patients with central nervous system diseases. The high efficiency of using cortexin is shown to be due to a combination of nootropic, neurotrophic, neuroprotective, reparative, and anticonvulsive effects, as well as antioxidant, metabolic, and antistress activities, which determines its high therapeutic efficacy in multimodal correction. 

The morphogenesis of additional smooth muscle structures of the visceral arteries of the fetus and placenta in its hypoplasia was examined to identify the features of their structure, localization, and values for circulation. Histological, histochemical, and morphometric studies were used to investigate the fragments of ventricles, lung, liver, kidney, brain, placenta, and umbilical cord from 34 fetuses that had died from chronic placental insufficiency at 28–29 weeks’ gestation. A comparison group included 10 cases in the same period, fetal and placental masses, and gestational age. The development of a set of smooth muscle structures of the inner coat of vessels is shown to be stimulated in the arterial bed of the fetus and placenta in placental hypoplasia in circumstances where the terminal villi and lumen of their capillaries are reduced. The regulatory adaptive elements involved in arterial luminal changes are divided into polypoid cushions, sphincters, and intimal muscles; they promote the rational distribution of blood streams in the organs and placenta, by reducing trophic and oxygen deprivation in the fetus. 

The results of following up infants with intrauterine infections and malformations were retrospectively analyzed. Infants with malformations were diagnosed as having congenital cytomegalovirus infection and congenital toxoplasmosis in 127 and 69 cases, respectively. The aim of the study was to characterize malformations in infants with congenital cytomegalovirus and congenital Toxoplasma infections. The infants with malformations in congenital cytomegalovirus infection were found to have higher mortality rates (61,4%) than those with congenital toxoplasmosis (34,8%). Postmortem analysis indicated that there was a predominance of embryopathies in infants with congenital cytomegalovirus infection and that of fetopathies in those with congenital toxoplasmosis. The dead infants with congenital cytomegalovirus infection had more commonly developed visceral defects, including heart diseases, pneumopathies, gastrointestinal and genitourinary abnormalities; fetopathies of the central nervous system and eye were prevalent in congenital toxoplasmosis. The surviving children with congenital toxoplasmosis were more frequently observed to have disabling CNS and ocular sequels as obstructive hydrocephalus, infantile cerebral palsy, complete or partial blindness, and cerebrasthenic disorders than those with congenital cytomegalovirus infection. 

The paper comparatively analyzes the Federal State Statistics Service’s (Posstat) data on stillbirth rates in the Russian Federation and its federal districts in 2010 and 2012. It is established that there is a preponderance of an antenatal component in the pattern of stillbirth in all the districts. According to the Rosstat data, the most common cause of stillbirth is fetal hypoxia that amounted to 74,6% and 73,9% of the total stillbirths in 2010 and 2012, respectively. The increase in the total stillbirth rates in 2012, by considering the fetal deaths occurring in earlier stages (at 22 to 28 weeks’ gestation), was attended by a decline in the proportion of stillbirths due to hypoxia and by a rise in the proportion of congenital malformations as a cause of death. 

The article presents the results of an investigation of the frequency of genetic markers of the folate cycle in 24 neonates with the hypotrophic or hypoplastic types of intrauterine growth retardation (IUGR). The investigators examined the polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene, such as S677S, C677T, and T677T, the methionine synthase (MTR) gene, such as A2756A, A2756G, and G2756G, and the methionine synthase reductase (MTRR) gene, such as G66G, G66A, and A66A. The analysis established an association of the occurrence of IUGR in neonates with MTHFR T677T, MTR G2756G, and MTRR A66A polymorphisms; this is especially relevant in the hypotrophic type of IUGR and in boys. Identification of risk groups and genetic analysis of folic acid metabolism allow the choice of an effective package of measures to prevent IUGR. 

Two Azerbaijani families were examined to determine the nature of neonatal hyperbilirubinemia. Blood samples from neonatal infants with jaundice, their siblings, and parents were an object of this investigation. The pedigrees of the probands were compiled and analyzed. The levels of hemoglobin, red blood cells, and bilirubin and the activity of glucose-6-phosphate dehydrogenase (G6PD) were determined; DNA sequencing of the G6PD gene was carried out. The probands were found to have G6PD deficiency and to be hemizygous for this gene. In probands’ families, the parents and siblings were also established to be homozygous, heterozygous, and hemizygous. The examined families showed two Mediterranean G6PD gene variants: c.563 C>T and c.1311 C>T, which influenced the clinical polymorphism of G6PD deficiency. The determination of total and conjugated bilirubin levels and G6PD activity in newborn infants may reduce the severe consequences of hyperbilirubinemia and prevent the risk of irreversible neurological disorders caused by jaundice. 

Studies of arterial hypertension in adults could identify factors aggravating its course and increasing the risk of poor outcomes as myocardial infarction, stroke, etc. Myocardial hypertrophy is a major marker for disease severity in children. It may be underestimated in certain situations, in obesity in particular. This investigation analyzed the impact of the most common myocardial mass (MM) indices on the detection rate of myocardial hypertrophy in hypertensive adolescents: 1) ММ/Height2,7 (>45 g/m2,7); 2) ММ/Height2,7(>48 g/ m2,7), 3) MM/Height2,7 (>51 g/m2,7); 4) zMM(F) (>1,65); 5) ММ/BSA(>115 g/m2); 6) MM/Body weight (>3,0 g/kg). The findings depended on the used index and varied from 11,3 to 35,9%. The myocardial mass correlated with systolic blood pressure and exercise time. Hypertrophy was frequently encountered in persistent hypertension (28,6%; p<0,05) and obesity (p<0,05). ММ/Height2,7(>48 g/m2,7) and zMM(F) (>1,65) are the most adequate indices for the detection of myocardial hypertrophy in these patients. 

The paper estimates the subpopulation composition of peripheral blood lymphocytes in children residing in differently radionuclidecontaminated regions in different periods after the Chernobyl accident. The irradiated parents’ posterities (children from the parents living in the areas where the soil is polluted with a radioactive 137Cs level above 1665 kBq/m2) have been found to have antitumor defense activation that is characterized by higher CD16+ lymphocyte counts; the activation is less marked in children residing in the areas with a 137Cs soil contamination level below 1665 kBq/m2. There is a tendency towards lower counts of the cells involved in leukocyte activation with a pluripotency marker (cells with the marker CD38) and lower proliferating cells (cells with the marker CD71) in children from differently polluted areas. Virtually all the children from radionuclide-contaminated areas show higher relative counts of cells with an apoptotic marker (CD95+ lymphocytes). 

The paper describes the steps and problems of diagnosing congenital myopathy with early respiratory disorders. While differentially diagnosing, the authors consider congenital myopathies, in which early cardiac involvement is encountered. Since the course of the disease in an observed female patient differed from that of such nosological entities and appeared as not only muscle weakness, but also as early respiratory disorders, we could not identify what nosological entity the disease belonged to in view of its clinical presentation and the results of muscle histological examination and we decided to perform exome sequencing. Molecular genetic testing could find heterozygous mutations in the titin (TTN) gene. The findings are suggestive of congenital proximal myopathy with early respiratory failure, which is an allelic variant of Salih myopathy. This case is the first and so far only description of this disease in Russia. 

The article presents the state of the problem of acute flaccid paralysis (AFP) in the world and Russia. It emphasizes the relevance of clinical and epidemiological surveillance of all diseases accompanied by AFP syndrome in children under 15 years of age. A clinical observation of a child diagnosed with spinal muscular atrophy is used as an example to consider the differential diagnosis of AFP and hereditary neuromuscular diseases. 

In the past decades, there have been publications suggesting the positive effect of organic farming food products on the health of children, including allergic persons. The paper presents the results of assessing the tolerance of BIBICALL organic fruit-and-vegetable purées in atopic dermatitis infants of the first year of life. A pilot open-label uncontrolled trial was conducted in 80 healthy full-term babies aged 5 tо 10 months with atopic dermatitis who were breast or formula fed; their diet was tightly controlled in 22 infants. When additional foods were given, 78 patients were observed to have no exacerbation throughout the follow-up. It is concluded that organic food products even with high sensitizing activity (such as carrot purée) may be added to the diet of babies with atopic dermatitis remission in the absence of sensitization, gastrointestinal tract dysfunction. Addition of ORGANIC vegetable and fruit purées was shown to have a significant favorable regulatory impact on gastrointestinal function, which showed as normalization of motor disorders (including colic χ2=20,31; p<0,05, regurgitation χ2=18,37; p<0,01), tympanism (χ2=4,99; p<0,05), and adequate digestion. 

Gilbert’s syndrome is a common genetic disease caused by deficiency of the liver enzyme UDP-glucuronyl transferase. The objective of the investigation is to study pathology of different portions of the gastrointestinal tract in children with Gilbert’s syndrome. A total of 182 children aged 3 to 17 years with Gilbert’s syndrome, who had been admitted to the clinic with the signs of jaundice and different gastroenterological complaints and symptoms, were examined. According to comprehensive examination results, among the gastrointestinal diseases in the patients, there was a preponderance duodenal injuries (41,5% of all diagnoses), there were less common injuries of the stomach (23,7%), esophagus (20%), and large bowel (14,8%). There was an age-specific relationship of the rate of erosive-ulcerative lesion of the upper gastrointestinal tract: erosions and ulcers were much more frequently encountered in children older than 10 years, predominantly in 14-17-year olds. Thus, the duodenum has been established to be most commonly affected in children with Gilbert’s syndrome. The children with this syndrome belong to a group at increased risk for gastrointestinal tract diseases. It is important to initiate measures as early as possible to prevent gastrointestinal tract diseases in children with Gilbert’s syndrome. 

This article analyzes morbidity rates and developmental outcomes in very premature infants in the first 3 years of life. A total of 2860 premature infants, including 1386 infants with birth weight less than 1500 g, in the 1997–2008 and 2008–2014 periods were examined. In the past 10 years, improvement of nursing tactics for very premature infants has led to a considerable reduction in the rate of prematurity-related diseases: chronic respiratory diseases, severe neurological disorders, and severe retinopathy, as well as to an improvement of physical psychomotor development indices by 3 years of life. Emphasis is laid on the importance of a three-step follow-up system in timely detecting a disease and defining the optimal tactics of early intervention.