Introduction. Spinal muscular atrophy (SMA) is among the most severe inherited neuromuscular diseases. The development of pathogenetic treatment methods, including gene therapy, and their widespread clinical adoption has ushered in a new era in SMA treatment, making it possible not only to halt the progression of the disease but also to improve patients’ functional capabilities.

Aim: to evaluate the efficacy of gene therapy in a real-world clinical practice with a 2-year follow-up study of patients with SMA type I who received treatment with onasemnogene abeparvovec.

Materials and methods. The study included 73 patients with SMA type I. The disease was confirmed by molecular genetic testing.The diagnosis of SMA type I in 22 patients (30.1%) was established due to the development of the clinical picture of the disease and after confirmatory DNA diagnostics. In 51 patients (69.9%), initially identified as part of expanded neonatal screening, the diagnosis was established immediately after the onset of the first SMA symptoms. The mean age at the time of gene therapy was 2.78±1.87 months (95% CI 2.35–3.22), min 1.00, max 7.00. A comprehensive assessment of treatment effectiveness included clinical (the main the motor development milestones according to WHO, HINE-2 and CHOP-INTEND scores) and electroneuromyographic (latency, amplitude and area of the negative peak of the distal compound muscle action potential during electrical stimulation of the ulnar nerve at the wrist, the motor nerve conduction velocity of the ulnar nerve on the forearm) parameters before the initiation of gene therapy and 6, 12, 18 and 24 months after its implementation.

Results. Following gene therapy, a large number of patients with SMA type I were able to achieve basic motor skills: 42.5% had good head control in the prone position; 78.1% rolled over from a supine to prone position; 47.2% sitting without support; 31.9% standing with assistance; 23.2% hands-&-knees crawling; 20.0% walking with assistance; 13.2% standing alone; 5.7% walking alone. However, most patients reached motor development milestones later than the WHO standards. By the end of the observation period, the HINE-2 score in patients with SMA type I significantly increased and amounted to Me 18.50 (16.00–24.00) points, with three children achieving the maximum score. The CHOP-INTEND scale score also increased significantly and amounted to Me 60.00 (58.00–64.00) points by the end of the 2-year observation period, with 17 children (23.3%) achieving the maximum score. Before gene therapy, patients with type I SMA had low values of the amplitude [Me 0.32 mV (0.15–0.81)] and area [Me 0.80 ms×mV (0.36–1.70)] of the compound muscle action potential. 24 months after gene therapy, the values of the amplitude and area significantly increased [Me 0.80 mV (0.60–1.20) and Me 1.40 ms×mV (1.00–2.10), respectively]. However, they did not reach the electroneuromyographic values of children without neurological pathology. During clinical and electroneuromyographic assessment in the dynamics of 2-year follow-up, it was not possible to establish statistically significant differences in patients with SMA type I depending on the onset of expanded neonatal screening.

Conclusion. Gene therapy in patients with SMA type I results in significant improvements in motor development. Despite persistent delays in motor skill development, a large number of patients achieved key milestones in early motor development, as demonstrated by significant increases in HINE-2 and CHOP-INTEND scores and improved electroneuromyographic parameters.

Introduction. In children, cardiomyopathies with a morphofunctional phenotype similar to sarcomeric hypertrophic cardiomyopathies are associated with various syndromes and diseases in almost half of cases, and for some of these nosologies, etiopathogenetic therapy is currently possible.

Aim: to determine the clinical, laboratory-instrumental, and genetic characteristics of the most common monogenic orphan diseases accompanied by a hypertrophic cardiomyopathy phenotype in children.

Methods. The study included 335 patients diagnosed with hypertrophic cardiomyopathies who were regularly followed up at the cardiology department of the National Medical Research Center for Children’s Health, Ministry of Health of the Russian Federation, from 2014 to 2025. All patients underwent molecular genetic analysis of target genomic regions containing 420 genes, in which pathogenic variants have been described in patients with a hypertrophic cardiomyopathy phenotype, using high-throughput sequencing. According to the study design, a comparative analysis of the course of the hypertrophic cardiomyopathy phenotype in children was performed based on the etiological cause—within the framework of inherited metabolic disorders, due to mitochondrial pathology, and RAS-pathy syndromes (n=114).

Results. Molecular genetic examination of patients with a hypertrophic cardiomyopathy phenotype verified rare hereditary diseases, including mitochondrial disorders (causal variants in mitochondrial or nuclear DNA), Pompe disease, Danon disease, PRKAG2 syndrome, and various RAS-pathy syndromes. A comparative characterization was performed, showing a high frequency of the hypertrophic cardiomyopathy phenotype in children with early-onset RAS-pathy syndromes. Myocardial hypertrophy exceeding 30 mm was rarely recorded; a symmetric form of the disease was significantly more common in mitochondrial pathology, asymmetric in RAS-pathy syndromes, and biventricular in inherited metabolic disorders. In addition to myocardial hypertrophy, patients with inherited metabolic disorders and mitochondrial pathology exhibited left ventricular dilation and reduced contractility. Patients with RAS-pathy syndromes had more pronounced (grade II–III) mitral regurgitation and a high frequency of pulmonary valve insufficiency (30.8%). Wolff–Parkinson–White syndrome (WPW) phenomenon and nonsustained supraventricular tachycardia were recorded in inherited metabolic disorders. In mitochondrial pathology, an increase in creatine phosphokinase-MB (CK-MB) with normal CK levels was noted; in inherited metabolic disorders, high values of CK, lactate dehydrogenase, and transaminases were observed. No significant difference in the frequency of elevation or in NT-proBNP levels was found between patients. Surgical treatment in the form of septal myectomy was performed mainly in RAS-pathy syndromes (23; 20%) and in one case of PRKAG2 syndrome. During the follow-up period, 17 (14.7%) children died; heart transplantation and cardioverter defibrillator implantation were performed in patients with Danon disease and PRKAG2 syndrome.

Conclusion. Myocardial hypertrophy in children may be the first symptom of numerous non-sarcomeric monogenic diseases with varying etiologies, prognoses, and treatments. Understanding the features of the hypertrophic cardiomyopathy phenotype course allows for differential diagnosis before molecular genetic results are available and enables timely treatment adjustments. The introduction of high-throughput sequencing into clinical practice allows simultaneous analysis of a large number of genes causing the hypertrophic cardiomyopathy phenotype, opening new possibilities for early diagnosis of rare diseases in children and providing a better evidence base for further research.

Introduction. Endoscopic diagnosis of eosinophilic esophagitis in children remains challenging due to insufficient familiarity among endoscopists with characteristic endoscopic findings, the non-specific nature of mucosal changes, and the necessity of differential diagnosis with other esophageal disorders.

Aim: to develop endoscopic differential diagnostic criteria for distinguishing eosinophilic esophagitis from other pediatric esophageal diseases.

Materials and methods. Differential diagnostic features were identified through retrospective analysis of upper endoscopy data from 102 children with histologically confirmed eosinophilic esophagitis (≥15 eosinophils/high-power field) and 110 pediatric controls with non-eosinophilic esophageal diseases: reflux esophagitis (n=62), esophageal candidiasis (n=32), and Crohn’s disease with esophageal involvement (n=16).

Results. Reflux esophagitis was characterized by longitudinal erosions predominantly localized to the distal third of the esophagus. White plaques were absent, and mucosal striation (both longitudinal and transverse) was mild and transient. Esophageal candidiasis presented with discrete white plaques exhibiting characteristic distribution and morphology, a preserved mucosal vascular pattern, and absence of striation; diagnosis was confirmed by cytological examination. Esophageal involvement in Crohn’s disease was distinguished by aphthous or linear ulcerations, longitudinal striation associated with mucosal healing, and a previously established diagnosis of Crohn’s disease. Marked eosinophil-predominant inflammation (≥15 eosinophils/hpf ) was exclusively observed in the eosinophilic esophagitis cohort and was absent in all control groups. eosinophilic esophagitis in children with comorbid neurological disorders exhibited endoscopic and histologic activity profiles comparable to those observed in neurologically intact pediatric patients.

Conclusion. The differential diagnostic features proposed herein enable reliable endoscopic distinction of eosinophilic esophagitis from esophagitis of alternative etiologies in children. Implementation of these criteria may enhance diagnostic accuracy for eosinophilic esophagitis, and reduce unnecessary invasive procedures in cases of non-eosinophilic esophagitis.

Phantom pain syndrome, which occurs in a significant proportion of patients after limb amputation, is a pathophysiologically complex pain phenomenon that significantly reduces the quality of life of patients. Recent data have convincingly proved that neuroplastic changes in the spinal cord are a critically important early link in the pathogenesis of this pathology.

This review presents an analysis of current understanding of the pathophysiological basis of spinal neuroplasticity in phantom pain syndrome after traumatic amputation. The contribution of central sensitization, structural reorganization and neuroinflammation to the formation of specific symptoms of the disease (spontaneous and stimulus-induced pain, somatotopic reorganization, etc.) is discussed. Special attention is paid to the analysis of the clinical significance of the discussed pathophysiological processes: from explaining the effectiveness of existing treatment methods to the prospects for the development of new targeted strategies aimed at modulating spinal neuroplasticity for the prevention of the development and therapy of the formed phantom pain syndrome.

Neurofibromatosis type 1 is an inherited neurocutaneous disorder occurring with an incidence of 1 in 2,000–4,000 newborns. Epilepsy is one of its neurological manifestations; however, data on its frequency, pathogenesis, and treatment approaches have not been fully elucidated. Aim: to summarize current data on the pathogenesis, clinical features, diagnosis and treatment of epilepsy in type I neurofibromatosis based on literature analysis and the results of our own prospective patient observation.

This article presents an analysis of current literature on epilepsy in neurofibromatosis type 1, including data on molecular mechanisms (the «second hit», hyperactivation of the Ras/Raf/MAPK and PI3K-mTOR pathways). In addition, we present the results of a prospective observational study of 724 patients with neurofibromatosis type 1 (aged 1 to 19 years) from 2021 to 2026. According to the literature, the prevalence of epilepsy in neurofibromatosis type 1 ranges from 4% to 14%. Focal seizures predominate (up to 83%). In our own cohort (n=724), epileptiform activity was recorded in 34 patients (4.7%), and epilepsy was diagnosed in 28 of these (82.4% of those with epileptiform activity). Among patients with epilepsy (n=28), focal seizures prevailed (82.1%), while structural changes on magnetic resonance imaging (MRI) were identified in only 14.3% of cases, which is consistent with international data. Remission was achieved in 67.9% of patients. The article also presents a clinical case of a 14-year-old patient with neurofibromatosis type 1, plexiform neurofibromas, and photosensitive focal epilepsy. Epilepsy in neurofibromatosis type 1 is relatively uncommon, but establishing the diagnosis and determining treatment strategies requires mandatory additional investigations, including MRI and video-EEG monitoring. The pathogenesis involves a combination of structural changes (gliomas, cortical dysplasias, hippocampal sclerosis) and molecular neuronal dysfunction resulting from hyperactivation of the Ras-MAPK and PI3K-mTOR pathways. The prognosis is generally favourable, and clinical remission can be achieved in most cases. Surgical treatment options should be considered in drug resistant forms of epilepsy. Patients with negative MRI findings are potential candidates for pathogenetic therapy with MEK inhibitors.

Introduction. Niemann-Pick disease type A (NPD type A) is the most severe form of acid sphingomyelinase deficiency, a rare inherited disorder of the lysosomal storage disorders with autosomal recessive inheritance caused by biallelic pathogenic variants in the SMPD1 gene. Since 2023, enzyme replacement therapy with olipudase alfa has been used to treat patients with NPD in Russia. This therapy does not alter the prognosis for neurological forms of the disease, as it does not penetrate the blood-brain barrier. Therefore, the only effective treatment, along with symptomatic therapy, for the systemic manifestations of NPD type A is hematopoietic stem cell transplantation, which does not prevent central nervous system damage. Early laboratory diagnostics using biochemical and molecular genetic diagnostic methods are crucial for timely diagnosis and treatment of patients with this form of the disease.

Aim: to describe intrafamilial polymorphism of clinical symptoms of NPD, type A using the example of two siblings from the same family.

Materials and methods. Clinical observation and diagnostics were conducted at the National Medical Research Center for Children’s Health of the Russian Ministry of Health from 2012 to 2026 in a single family in which the first proband with clinical symptoms characteristic of NBP type A was identified in 2012. Acid sphingomyelinase activity was measured in dried blood spots using tandem mass spectrometry, and nucleotide variants in the SMPD1 gene were identified using Sanger sequencing. Familial segregation analysis was performed for the proband and eight family members.

Results. Diagnosis of the first proband revealed a significant decrease in acid sphingomyelinase activity in the patient’s spinal cord. Sequencing revealed the presence of two pathogenic heterozygous variants in the SMPD1 gene: c.996del (p.Phe333Serfs52) and c.1252C>T (p.Arg418). Carriage of the pathogenic causative variants in the SMPD1 gene was confirmed in the parents. The second proband was diagnosed on the second day of life. As a result of the timely diagnosis, immunotherapy (bone marrow transplant) was prescribed, which determined the child’s prognosis.

Conclusion. Using two siblings from the same family as an example, polymorphism in the clinical symptoms of NPD type A was demonstrated. Early diagnosis of this form of the disease significantly improves the prognosis and enables timely initiation of therapy.