Vol 14, No 3 (2023)

Congenital hyperinsulinism is a rare hereditary disease characterized by inadequate hypersecretion of insulin by pancreatic β-cells, clinically manifested by persistent hypoglycemia, which poses a great threat to patient survival and a high risk of developing severe neurological complications.

The article presents the results of clinical, hormonal and molecular genetic examination and treatment of 10 patients with congenital hyperinsulinism caused by mutations in the genes of ATP-dependent potassium channels (KCNJ11, ABCC8), hospitalized in Saint Petersburg State Pediatric Medical University clinic in 2010–2023. In all the studied patients, the disease manifested from the 1^st to the 3^rd day of life, and the median age of diagnosis of congenital hyperinsulinism in the study group was 1 month (min 14 days; max 3 years 9 months). In 8 out of 10 patients, a severe course of hypoglycemic syndrome was noted at the onset of the disease. According to the molecular genetic investigation results, 8 different mutations were identified: in the KCNJ11 (2/8) and ABCC8 (6/8) genes. Identical variants were found in two pairs of related patients. In children with mutations in the ABCC8 gene (n = 8), 2 variants with unknown clinical significance were identified, which were not previously described in allelic databases and scientific literature. According to the analysis of anamnestic and clinical and laboratory data, 80.0% of children, including patients with new, previously not described in the scientific literature, variants in the ABCC8 gene have a severe progressive course of congenital hyperinsulinism, requiring the appointment of insulinostatic therapy.

BACKGROUND: One of the tasks of modern medicine is to reduce the level of perinatal losses, for which it is necessary to know their main causes.

AIM: To determine the course of an infectious disease in the genesis of perinatal losses.

MATERIALS AND METHODS: In order to determine the role of infection in the genesis of perinatal losses, a retrospective study was conducted with two groups: the main group — 307 women with perinatal fetal death, the control group — 357 women without perinatal losses. An analysis was also made of the data of the statistical form No. 32 (annual) “Information on medical care for pregnant women, women in childbirth and puerperas”, presented by the Medical Information and Analytical Centers of St. Petersburg and the Leningrad Region for 2006–2018 and annual reports of the Leningrad Regional Pathological Anatomical Bureau for 2006–2016.

RESULTS: In 2006–2018, the leading causes of perinatal death were intrauterine hypoxia and asphyxia during childbirth (ICD 10: P20, P21), that is, not diseases, but symptomatic conditions. Such features of reporting documentation complicate the analysis of the causes of perinatal losses and the implementation of a set of preventive measures, including at the state level. Also, according to the official report, it is impossible to assess the contribution of a specific virus and a specific localization of the lesion to the genesis of perinatal losses. In the main group, hematogenous viral and ascending bacterial infection of the placenta was detected 4 times more often. With a combination of bacterial and viral infection of the placenta, the risk of a fatal outcome increases. Infectious pathogens most frequently encountered in perinatal losses have been established.

CONCLUSIONS: The cause of more than half of the cases of perinatal losses in women who gave birth in maternity hospitals in St. Petersburg and Leningrad Region in 2009–2018 is an infectious pathology: viral, bacterial and viral-bacterial, and not intrauterine hypoxia/asphyxia during childbirth, as stated by the official statistics. In this regard, the main direction in the prevention of perinatal losses is the timely detection and treatment of infectious pathology.

BACKGROUND: The interest in infectious mononucleosis caused by the Epstein–Barr virus (EBV) is currently apparent. Epstein–Barr virus reaches tropism for reticular and lymphoid tissues, does not eliminate from the body and causes an immunopathological process in which the endocrine system develops. Thyroxine (T₄), triiodothyronine (T₃), and thyroid-stimulating hormone determinations are the most widely used diagnostic tests to assess thyroid function.

AIM: To study changes in T₃, T₄, thyroid-stimulating hormone in children of older sex and age at the height and convalescence of infectious mononucleosis, the period of Epstein–Barr virus.

MATERIALS AND METHODS: Under the supervision of the child were 94 aged from 1 to 17 years, among them from 1 to 5 years – 22%, from 5 to 10 years — 39%, from 10 to 15 years — 27%, from 15 to 17 years — 12% , diagnosed with Epstein–Barr virus – mononucleosis, moderate severity. The diagnosis was made on the basis of clinical, anamnestic and laboratory data. The studies leading to the diagnosis were carried out in the laboratory of the Saint Petersburg State Pediatric Medical University. In addition to routine settings (clinical minimum), detection of M- and G- antibodies to Epstein–Barr virus, detection of the genome in the blood by PCR, determination of the levels of T₃, T₄, thyroid-stimulating hormone by enzyme-linked immunosorbent assay in blood serum.

RESULTS: Regular changes in T₃ concentrations were registered in both girls and boys of all three age groups: the concentration of T₃, T₄ in the period of the peak of the disease was reduced compared to the period of convalescence. Significant changes in thyroid-stimulating hormone were registered in girls and boys of all three age groups: the concentration of thyroid-stimulating hormone during the peak of the disease slightly decreased compared to the period of convalescence in boys and increased compared to the period of convalescence in girls.

CONCLUSIONS: The changes in the levels of T₃, T₄, thyroid-stimulating hormone in children during the peak of infectious mononucleosis depends on the severity of the disease, the presence and nature of complications.

BACKGROUND: There is little information concerning the health parameters of children who are in the conditions of military hostilities.

AIM: The aim of the study is to develop and study the impact of a comprehensive integration and rehabilitation program on heart rate variability in primary school children who have experienced the stress of military operations.

MATERIALS AND METHODS: 128 children of primary school age who found themselves in the zone of active hostilities were under observation. The comparison group consisted of 68 children who lived in territories where military operations were not carried out. The assessment of vegetative functions was carried out according to the indicators of the analysis of temporal and spectral indicators of heart rate variability using the hardware and software complex Poly-Spectrum-12.

RESULTS: The power of the “very” low-frequency component (VLF, ms²) of the spectrum in group I of children was also increased by 23.79% in comparison with the comparison group. The respiratory component (HF, ms²) of the general spectrum also had a statistical difference (25.27%) with the indicators of the comparison group at the time of the first study (p < 0.05) in the younger schoolchildren evacuated to Rostov-on-Don. Upon repeated examination, it was found that the indicators of mode and variation range increased in all subgroups, except for a subgroup of children who were in the combat zone and were not included in the comprehensive integration and rehabilitation program.

CONCLUSIONS: According to the results of spectral and temporal analysis of the heart rate, the vagosympathetic balance in younger schoolchildren who experienced the impact of the military operation in the Donbass Region reflects the activation of the sympathetic department of the autonomic nervous system. The developed comprehensive integration and rehabilitation program has shown its greatest effectiveness in children evacuated to Rostov-on-Don.

BACKGROUND: The evolutionarily formed biomechanism of childbirth in humans causes a high incidence of head injuries during the reproductive process. One of the indicators of cranial injury is cephalohematoma. Despite the presence of a number of protective and adaptive mechanisms on the part of the fetus, the frequency of subperiosteal hemorrhages remains high and does not tend to decrease. Modern knowledge about the etiology of cephalohematomas does not always fit into the framework of classical ideas about the causes of hemorrhage under the periosteum. The lack of a unified understanding of the pathomechanisms occurring in a long-term subperiosteal hemorrhage leads to a mismatch of tactical actions during their treatment and the development of complications.

AIM: To assess the role of etiological factors in the formation of subperiosteal hemorrhage in newborns and to determine the main direction of the pathophysiological process during repair with various types of cephalohematomas and methods of treatment.

MATERIALS AND METHODS: A study of 243 newborns with the presence of cephalohematomas of various localization for the period from 2018–2022 was carried out, an analysis of the etiological prerequisites, features of the reparative process with various volumes of hemorrhages and methods of treatment using descriptive statistics methods was carried out.

RESULTS: The predominance of children with the presence of cephalohematomas with a history of the absence of hydraulic protection of the head due to early rupture of amniotic fluid was revealed in relation to other mechanical factors of intranatal damage. The greatest number of subperiosteal hemorrhages was noted in newborns from multiparous mothers. The main non-traumatic factor contributing to the formation of cephalohematomas was the factor of infectious effect on the fetus. The predominance of osteomalacic processes with medium and large volumes of cephalohematomas in relation to small-sized cephalohematomas, which had a tendency to early ossification, was noted. The effectiveness of therapeutic aspiration was noted in all cases of observation of newborns from the surgical subgroup.

CONCLUSIONS: One of the most significant etiological factors for the occurrence of cephalohematomas in the observation group was the factor of intranatal mechanical trauma to the soft tissues of the head, due to the lack of hydraulic protection. The numerical predominance of newborns with subperiosteal hemorrhages from multiparous mothers contradicts the basic physiological canons of the biomechanism of labor and may be due to the high incidence of the infectious factor. The direction of the pathophysiological process in the course of repair in case of periosteal detachment may depend not only on microenvironmental factors, but also be determined by the amount of hemorrhage. The use of puncture treatment for cephalohematomas can significantly reduce the number of complications associated with long-term persistence of subperiosteal hemorrhage.

Neuroblastoma is the most common extracranial solid tumor in childhood, accounting for 8–15% of all malignant neoplasms in children. The uniqueness of the neuroblastoma etiology and pathogenesis creates significant difficulties for doctors due to the unpredictability of the course of the disease: the tumor can regress and lead to death in a short time, showing significant immunity to ongoing therapy. Early diagnosis of a tumor is necessary to understand the risk factors, the etiology, the mechanisms of neuroblastoma occurrence and further development. To date, a number of different risk factors have been identified, related both to genetic aspects and to aspects related to the course of pregnancy, birth and lifestyle of the child’s parents. The list of these risk factors is still incomplete and research to identify new factors continues to this day. Morphological and molecular genetic diagnostics play an important role in this. Undifferentiated and low-differentiated variants of neuroblastoma are often associated with MYCN amplification and other chromosomal aberrations determined by molecular genetic research. Chromosomal instability plays an important role in the process of early tumor development, which probably causes the possibility of acquiring certain genetic changes, which also determines the prognosis and further therapeutic options. In this article, we have identified the most significant risk factors by comparing the results of various studies.

Kabuki syndrome is a rare hereditary disease that has a specific clinical picture: facial features, growth retardation, muscular hypotonia, skeletal abnormalities, dermatoglyphic abnormalities, mild to moderate mental retardation, and postnatal growth deficiency. Kabuki syndrome (Kabuki mask syndrome / Kabuki makeup syndrome) got its name for the specific features of the appearance of patients who have a facial expression similar to a special makeup that highlights the eyes and eyebrows of the characters of the Japanese Kabuki theater. The main reasons for the development of Kabuki syndrome in 75% are mutations in the KMT2D gene (KS type 1) and in 5% are mutations in the KDM6A gene (Kabuki syndrome type 2), the etiology of about 20% of cases remains unknown. Most mutations in type 1 Kabuki syndrome are formed de novo, and cases of autosomal dominant inheritance have also been described. Type 2 Kabuki syndrome has sex-linked (X-linked) inheritance. Because Kabuki syndrome is a low-prevalence, multisystem disease, patients require a variety of diagnostic and screening tests with multidisciplinary evaluation of outcomes at different stages of their lives. Early diagnosis of the disease is crucial for timely treatment and rehabilitation measures and improving the prognosis and quality of life of the child. The interest of the presented clinical observation of Kabuki syndrome lies in the importance of early recognition of clinical manifestations, timely surgical treatment, hearing rehabilitation and improving the prognosis of the patient’s life. The article describes a clinical observation, genetically confirmed type 1 Kabuki syndrome, in a child born in 2015 (type of inheritance not established). The interest of the presented clinical observation of Kabuki syndrome, manifested by characteristic facial features, skeletal anomalies, postnatal growth retardation, dermatoglyphic anomalies, intellectual retardation, lies in the need for a multidisciplinary approach to the diagnosis and treatment of the patient.

Mayer–Rokitansky–Küstner–Hauser syndrome is a congenital anomaly in the development of the female reproductive system, the essence of which is a violation of the intrauterine development of the Müllerian ducts, causing complete aplasia of the vagina and uterus. Deviation is a total or partial absence uterus, two upper thirds of the vagina, most often in combination with various anomalies of organs and systems, such as excretory, cardiovascular. Currently, the causes of this pathology are not fully understood studied. According to the World Health Organization, the percentage of hereditary factors intrauterine development disorders is approximately 10 to 25%. It is known that patients with this pathology often suffer from diseases of the urinary system (pyelonephritis). Chronic pyelonephritis is a common pathology in any age group due to excessive growth of the bacterial flora. The main causative agent, most often, are representatives of the intestinal microbiota (Escherichia coli, Enterococcus, Staphylococcus). Determination of the genus and species composition of the intestinal microbiota can serve as one of the diagnostic signs that contribute to the timely correction of the main therapy. Presented clinical case demonstrates a change in the biodiversity of the intestinal microbiota in a patient with Mayer–Rokitansky–Küstner–Hauser syndrome, which entails timely correction of drug therapy regimens in relation to chronic pyelonephritis and achieving remission. Thus, the study of changes in the composition of the intestinal microflora can become a new criterion in the diagnosis and treatment of this disease at an early stage.