Наследственная тирозинемия 1-го типа, или гепаторенальная тирозинемия, – тяжелое орфанное аутосомно-рецессивное заболевание с нарушением обмена тирозина, вызванное дефицитом фермента фумарилацетоацетатгидролазы (fumarylacetoacetate hydrolase, FAH). Заболевание встречается с частотой 1:100 000-1:120 000 случаев живорождения, в ряде регионов (например, на территории Чеченской Республики) наследственная тирозинемия 1-го типа может встречаться значительно чаще. При наследственной тирозинемии 1-го типа отмечается повышение тирозина, сукцинилацетона и других токсических метаболитов в крови, а также их накопление в органах-мишенях, что приводит к поражению печени с развитием цирроза и печеночно-клеточной недостаточности, почечных канальцев – с развитием синдрома Фанкони и гипофосфатемического рахита, а также центральной нервной системы. В ряде случаев в патологический процесс может вовлекаться миокард с формированием гипертрофической кардиомиопатии. Заболевание представляет большую сложность для дифференциальной диагностики ввиду полиорганности поражения, частого сочетания с другими наследственными патологиями. Лечение наследственной тирозинемии 1-го типа на современном этапе основано на применении элиминационной диетотерапии и препаратов для патогенетической терапии. Активно изучаются возможности генно-инженерных методов в этиотропной терапии данного заболевания. В представленной статье описан случай острой формы наследственной тирозинемии 1-го типа у ребенка с множественными врожденными пороками развития центральной нервной системы, включающими в себя синдром Денди – Уокера, с нарушением формирования челюстно-лицевого аппарата, с проявлениями иммунодефицитного состояния и тяжелым генерализованным редицивирующим инфекционным процессом, обусловленным полирезистентной смешанной бактериально-грибковой флорой. Описана динамика неврологической симптоматики у пациента на первом году жизни на фоне патогенетической терапии основного заболевания, приведены лабораторные показатели функции печени. Hereditary tyrosinemia type 1 or hepatorenal tyrosinemia is a severe orphan autosomal-recessive disorder of tyrosine metabolism caused by a deficiency of the enzyme fumarylacetoacetate hydrolase (FAH). The disease is diagnosed in approximately 1:100 000-1:120 000 cases of live births, and in certain regions (such as the Chechen Republic in Russian Federation) the estimated frequency of diagnosis can be significantly higher. In hereditary tyrosinemia type 1, blood levels of tyrosine, succinylacetone and other toxic metabolites are increased, which results in the accumulation of the toxic metabolites in target organs causingliver damage with progressive development of liver failure and liver cirrhosis, damage to the renal tubules resulting in Fanconi syndrome and hypophosphatemic rickets, and central nervous system. In some patients, myocardium could be involved in the pathological process, resulting in the development of hypertrophic cardiomyopathy. The disease presents a great challenge for differential diagnosis due to its polyorganic nature and frequent combination with other hereditary disorders. The modern treatment of hereditary tyrosinemia type 1 includes an elimination-based diet and pathogenetic drug therapy. The potential of genetic engineering methods in target therapy of hereditary tyrosinemia type 1 is being actively researched. Within the article if presented a case of early onset hereditary tyrosinemia type 1 in an infant with multiple congenital defects of central nervous system, including Dandy – Walker syndrome, and congenital defects of maxillofacial area, with signs of an immunodeficiency state and a severe generalized recurring infectious process involving poly-resistant mixed flora. The dynamic changes of neurologic signs are provided for the first year of life of the patient receiving the pathogenetic therapy for the main disease. Laboratory findings are provided, showing the dynamic changes in liver function of the patient.

Prader–Willi syndrome (PWS) is a genetic disorder caused by a lack of expression of the paternally inherited chromosome 15q11.2-q13. PWS is a serious medical and social problem that requires the attention of a wide range of specialists. PWS is characterized by variability of symptoms and complex disease progression. The main clinical manifestation of the syndrome is severe hypotonia, or “floppy baby syndrome”, which is typical for the neonatal period. As a child grows, hyperphagia appears with the development of morbid obesity, as well as delay in growth, neuropsychiatric and sexual development, behavioral disorders, and cardiopulmonary complications. The diagnosis of the disease is based on clinical criteria and molecular genetic testing. The treatment of PWS is symptomatic. In addition to the use of growth hormone, examinations are carried out to evaluate the efficacy and safety of other groups of pharmacological agents for the treatment and correction of existing symptoms and complications of PWS. Timely diagnosis improves long-term outcomes and quality of life of children with this genetic pathology. The article presents current approaches to the diagnosis and management of patients with PWS. Key words: Prader–Willi syndrome, floppy baby syndrome, stigmas of dysembryogenesis, hypotonia, hyporeflexia, obesity, hyperphagia, neurodevelopmental disorders, hypogonadism

Objective. To demonstrate the clinical features of Prader–Willi syndrome (PWS) in the neonatal period, to assess the impact of perinatal factors on the development and severity of PWS, and to compare the data obtained with literary sources. Patients and methods. This cross-sectional open-label retrospective study was conducted between 2022 and 2023. It included 5 neonates with severe hypotonia and subsequently confirmed PWS. Anamnestic, anthropometric, age- and sex-related characteristics of children with PWS and anamnestic data of their mothers, as well as clinical manifestations of PWS were investigated. Results. Most of the children with PWS were born prematurely, with a mean birth weight of 2512.0 ± 549.5 g, height of 48.2 ± 5.1 cm, and head circumference of 32.9 ± 2.5 cm, which is below the standard values for preterm infants. The mean Apgar score was 5.8 ± 2.8/7.2 ± 1.9. Three out of five children were not appropriate for gestational age, having low values according to the INTERGROWTH-21st standards. Children were born to mothers aged 35 ± 5 years, and 3 (60%) out of 5 women had an aggravated somatic and/or obstetric and gynecological history. Evaluation of clinical manifestations of PWS revealed post-hypoxic injury of the central nervous system (CNS) (100%), respiratory disorders (100%), infectious toxicosis and intrauterine pneumonia (80%). Objective examination revealed hypotonia, hyporeflexia, reduced motor function in all patients, and 80% of children had poor sucking reflex. The most common phenotypic features were high forehead, almondshaped eyes, dolichocephaly, narrow temporal bones, thin upper lip, down-turned corners of the mouth; orbital hypertelorism, acromicria, and hypogonadism were observed less frequently. Conclusion. Early diagnosis of PWS is possible with a comprehensive differential diagnosis in children with the “floppy baby syndrome”. Special attention should be paid to children with intrauterine growth restriction, typical stigmas of dysembryogenesis, respiratory disorders, and hypoxic CNS injury. Genetic counseling and karyotyping should be performed as early as possible in all newborns with suspected PWS to prevent the development of complications. Key words: Prader–Willi syndrome, floppy baby syndrome, stigmas of dysembryogenesis, hypotonia, hyporeflexia, poor sucking reflex, feeding disorders, developmental delay, hypogonadism

Введение. Геморрагическая болезнь новорожденных – патологическое состояние новорожденных и детей первых месяцев жизни, обусловленное дефицитом витамин К-зависимых факторов свертывания крови и проявляющееся повышенной кровоточивостью. Частота возникновения геморрагической болезни новорожденных варьирует в разных регионах мира, в России, согласно литературным данным, она составляет от 0,25% до 1,7%. Для геморрагической болезни новорожденных характерно развитие кровотечений и кровоизлияний, которые негативно влияют на функцию и в дальнейшем на развитие ряда органов и систем ребенка, в особенности на центральную нервную систему и желудочно-кишечный тракт. Основываясь на этиологии развития заболевания, геморрагическая болезнь новорожденных классифицируется на первичную (идиопатическую) и вторичную. В зависимости от возраста дебюта выделяют раннюю, которая проявляется в первые 24 часа жизни, классическую (развивается на 2-7 сутки) и позднюю, проявляющуюся после 1 недели жизни (редко возникает до шести месяцев жизни, а некоторые авторы указывают возраст детей до 1 года), формы геморрагической болезни новорожденных. Ключевым приоритетом неонатологов является выделение из числа родившихся детей новорожденных, составляющих группу риска по геморрагической болезни новорожденных с целью профилактического введения им витамина К, что позволяет предотвращать тяжелые нежелательные последствия заболевания. Генетическое исследование методом логистического регрессионного анализа подтвердило более высокий риск внутрижелудочковых геморрагий у новорожденных при полиморфизмах в гене VKORC1, отвечающем за связывание витамина К1 цистеином и, таким образом, за снижение его концентрации у носителей данного гена. Несмотря на вариабельность в подходах к дозам, способам и срокам введения, парентеральное введение витамина К – единственный надежный и предпочтительный способ профилактики данного заболевания. В случае развития геморрагической болезни новорожденных в настоящее время разработаны современные подходы к диагностике и лечению данной патологии. Результаты. В статье приводятся современные подходы к профилактике, диагностике и терапии витамин К-зависимой геморрагической болезни новорожденных. Background. Hemorrhagic disease of the newborn is a pathological condition in newborns and children during the first months of life, caused by vitamin K deficiency of dependent blood coagulation factors and manifested by increased bleeding. The incidence of hemorrhagic disease of the newborn varies in different regions of the world, in Russia, according to the literature data, it ranges from 0.25 to 1.7%. Hemorrhagic disease of the newborn is characterized by the development of bleeding and hemorrhage, which negatively affect the function and further development of a number of organs and systems of the child, especially the central nervous system and the gastrointestinal tract. Based on the etiology of the development of the disease described above, HDN is classified into primary (idiopathic) and secondary. Depending on the age of onset, early is distinguished – it manifests itself in the first 24 hours of life, classical – develops on the 2-7th day and late, manifesting itself after 1 week of life (rarely occurs at the age of up to 6 months of life, and some authors indicate the age children under 1 year of age) hemorrhagic disease of the newborn forms. The key priority of neonatologists is to single out from the number of born children, newborns who are at risk for HRD for the purpose of prophylactic administration of vitamin K to them, which will prevent severe undesirable consequences of the disease.A genetic study using logistic regression analysis confirmed a higher risk of intraventricular hemorrhages in newborns with polymorphisms in the VKORC1 genes, which is responsible for the binding of vitamin K1 to cysteine, and thus for a decrease in its concentration in carriers of this gene. Despite the variability in approaches to doses, methods and timing of administration, parenteral administration of vitamin K is the only reliable and preferred way to prevent this disease. In the case of the development of hemorrhagic disease of the newborn, modern approaches to the diagnosis and treatment of this pathology have been developed. Results. The article presents modern approaches to the prevention, diagnosis and therapy of vitamin K-dependent hemorrhagic disease of the newborn.

Aim: Genetic, clinical, laboratory-instrumental and morphological characteristics of genetic dysfunctions of the surfactant system in children, therapy and outcomes of the disease. Design: Multicentre, ambispective, open-label, descriptive pilot longitudinal study. Materials and methods. We observed 17 children from 16 families with identified mutations in the SFTPC, ABCA3, NKX2-1 genes. Methods used: genealogical, Sanger sequencing, clinical exome sequencing, computed tomography and histological examination of the lungs. Results. The study included 8 children with congenital deficiency of surfactant protein C, 8 children with brain-lung-thyroid syndrome and 1 patient with congenital deficiency of protein ABSA3. Based on the results of a genetic examination of patients, nucleotide variants c.218T>C were identified in 2 out of 8 patients with a mutation in the SFTPC gene, which is the most common according to the literature. In 5 children, the mutations were hereditary. Congenital deficiency of surfactant protein C, ABCA3 protein and brain-lung-thyroid syndrome were characterized by clinical, computed tomography, and morphological signs of interstitial lung disease. Despite complex respiratory, anti-inflammatory therapy, the frequency of deaths in congenital deficiency of surfactant protein C was 37.5%. Conclusion. Children with severe respiratory distress syndrome of newborns, interstitial lung disease with the development of severe chronic respiratory failure, burdened with a family history should undergo genetic testing to detect mutations in the genes SFTPB, SFTPC, ABCA3. The patient's combination of respiratory symptoms with congenital hypothyroidism and neurological pathology is the basis for genetic examination for NKX2-1 gene mutations to exclude the brain-lung-thyroid syndrome. Keywords: genetic dysfunctions of the surfactant system, congenital deficiency of surfactant protein C, congenital deficiency of ABCA3 protein, brain-lung-thyroid syndrome, NKX2-1 gene, children.

Overdiagnosis of congenital infections caused by Human Herpesvirus 6A/B (HHV-6A/B) in newborns with an inherited chromosomally integrated (ici) HHV-6A/B creates an unreasonable economic burden for the healthcare system and society. We assessed economic significance of detection and laboratory confirmation of iciHHV-6A/B in newborns with congenital infections during their inpatient treatment in Moscow in 2020. The introduction of a new method based on the quantitative detection of HHV-6A/B DNA in patient’s whole blood sample, nail plates and/or hair follicles by a real-time polymerase chain reaction will result in an economic effect with a minimum ratio of 1:68, will reduce healthcare costs in Moscow and optimize the epidemiological surveillance of vertically congenital infections in the region. The total estimated economic costs averted (including costs of pharmacotherapy, as well as clinical, laboratory, and instrumental examinations and other medical procedures in maternity and obstetric hospitals) will be approximately 6 million rubles per year for Moscow. Key words: economic significance, economic costs averted, Human Herpesvirus 6A/B, inherited chromosomally integrated Human Herpesvirus 6 A/B, newborns, congenital infections

The article presents data about maternal and prenatal influences lead to «programming» of arterial hypertension (AH) in the child's later life. A special group that is threatened by the development of AH at an older age is premature children and children with intrauterine development delay due to a small number of nephrons and the launch of prenatal programming of hypertension. The state of the mother's health before conception, as well as the use of assisted reproductive technologies, despite a normal pregnancy in general and the birth of a healthy newborn can provoke the development of hypertension in childhood.

The article is devoted to the study of features of lower respiratory tract infection associated with respiratory syncytial virus. 40 cases of RSV-bronchiolitis in preterm children under year with/without bronchopulmonary dysplasia were analyzed. It was established that disease in those groups of patients had severe course because of the respiratory failure, which dominates in clinical pictures as symptoms of bronchial obstruction and apnea. Treatment of severe RSV-infection often demand admission to intensive care unit, supplemental oxygen and/or mechanical ventilation.

The article is devoted to the study of features of lower respiratory tract infection associated with respiratory syncytial virus. 40 cases of RSV-bronchiolitis in preterm children under year with/without bronchopulmonary dysplasia were analyzed. It was established that disease in those groups of patients had severe course because of the respiratory failure, which dominates in clinical pictures as symptoms of bronchial obstruction and apnea. Treatment of severe RSV-infection often demand admission to intensive care unit, supplemental oxygen and/or mechanical ventilation.

The article is devoted to the study of features of lower respiratory tract infection associated with respiratory syncytial virus. 40 cases of RSV-bronchiolitis in preterm children under year with/without bronchopulmonary dysplasia were analyzed. It was established that disease in those groups of patients had severe course because of the respiratory failure, which dominates in clinical pictures as symptoms of bronchial obstruction and apnea. Treatment of severe RSV-infection often demand admission to intensive care unit, supplemental oxygen and/or mechanical ventilation.

The article is devoted to the study of features of lower respiratory tract infection associated with respiratory syncytial virus. 40 cases of RSV-bronchiolitis in preterm children under year with/without bronchopulmonary dysplasia were analyzed. It was established that disease in those groups of patients had severe course because of the respiratory failure, which dominates in clinical pictures as symptoms of bronchial obstruction and apnea. Treatment of severe RSV-infection often demand admission to intensive care unit, supplemental oxygen and/or mechanical ventilation.

Objective — to study the influence of chlamidia infection on the course of pregnancy, childbirth and the condition of newborns. Research was performed prospectively and retrospectively. It included 241 pregnant women. It is proved, that women with anamnesis of urogenital chlamidia infection have significantly higher risk of the complicated course of pregnancy concerning the threat of abortion, disturbances of a condition of fetoplacental complex. Strong connection between the development of hydramnion, bleeding in the afterbirth and postnatal period, and also disturbances of functional system mother-placenta-foetus during CT and the examination of newborn condition was revealed. The obtained data of an objective estimation of prognostic and diagnostic characteristics of the factor — «anamnesis of urogenital chlamidia infection» — allow to consider it as a significant risk factor which is necessary for taking into account in planning of complex actions at all stages of medical observation.