Introduction. The Wilson–Konovalov disease (WKD) is a rare genetic disorder characterized by polymorphism of clinical manifestations and a progressive course with the development of irreversible and life-threatening conditions. The study of WKD phenotypes is complicated by the number of potential factors that play a role in its formation, their possible combination.

To identify the significance of these factors in the formation of clinical heterogeneity of the disease, it is advisable to conduct an analysis in siblings who not only have the same genotype, but are also under the influence of similar environmental factors.

Objective. To evaluate the features of intrafamilial clinical polymorphism of WKD in childhood siblings and determine the range of factors influencing the course of the disease.

Materials and methods. In a retrospective study, we analyzed the health data of twenty two sibs from 11 families: 1 pair of monozygotic twins and 10 pairs of full sibs with a diagnosis of WKD established on the basis of a molecular genetic study or the diagnostic algorithm “Leipzig, 2001”.

Results. The same phenotype was observed in 8 out of 11 families: in 7 families H2/H2, in 1 family-H2+N. A different phenotype was observed in 3 families: in one — with the development of fulminant hepatitis in one of the siblings, in the other two — with the presence of neurological changes in the older sibling (H2+N/H2). In the groups of patients with neurologic changes, the values of the mean age of onset and diagnosis of WKD were significantly higher than in the group of children without these manifestations. The mean ceruloplasmin level was 14.2 ± 10.2 mg/dL in older children and 12.8 ± 5.7 mg/dL in younger children, while the median 24-hour urine copper levels were 223.6 [35.8; 1301] μg/dL and 45.2 [5.8; 414] μg/dL, respectively. Patients with at least one “severe” mutation in the genotype had lower values of ceruloplasmin (p = 0.013) and high copper in daily urine (p = 0.02) compared to patients with two “mild” mutations in the genotype.

Conclusion. The phenotypic variability of WKD in sibs is formed mainly by the accession of neurologic changes and acute liver failure developed as a result of late diagnosis or environmental factors. The ATP7B gene genotype and some epigenetic modifications may also determine the clinical picture, but further studies are required to assess their contribution.

Contribution:
Komarova A.D. — concept and design, statistical processing, writing text;
Vorobyeva N.L. — collection and processing of material;
Dzhurtubaeva D.R. — collection and processing of material;
Potapov A.S. — research concept, text editing;
Savostyanov K.V. — research concept, text editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: November 12, 2024
Accepted: December 3, 2024
Published: January 31, 2025

Introduction. In children with spinal muscular atrophy (SMA), reliable indicators (biomarkers) are needed to predict the disease, which could reflect the underlying process of the disease. It is believed that the parameters of motor nerve conduction studies (MNCV) (amplitude and area of the compound muscle action potential (CMAP), the motor unit number estimation) may correlate with the degree of denervation in SMA and with the severity of motor disorders.

The purpose of the study. To detect the trend in MNCV parameters in SMA type I patients with clinical manifestations of the disease and children at the presymptomatic stage of the disease, against the background of treatment with onasemnogen abeparvovek.

Materials and methods. The study included sixty eight SMA children, including 42 boys (53.2%). All children received gene therapy with the onasemnogen abeparvovek. 33 children were treated at the presymptomatic stage (age at the time of treatment was 2.12 ± 0.91 years (95% CI 1.80–2.45), min — 1.00, max — 5.00). In 35 SMA type I children, treatment started when clinical symptoms of the disease were already present (age at the time of treatment was 3.40 ± 1.85 years (95% CI 3.10–4.25), min — 1.00, max — 7.00). All children included in this study underwent MNCV before the start of therapy and for the next 2 years. The amplitude of the negative peak of the CMAP from the abductor digiti minimi muscle during stimulation of the ulnar nerve and nerve conduction velocity (NCV) along the distal part of the ulnar nerve were determined. Due to the fact that the values of most of the MNCV parameters did not obey the normal distribution, they were described using the values of the median (Me) and the lower and upper quartiles (Q1–Q3), minimum (min) and maximum (max).

Results. In the cohort of presymptomatic patients, the CMAP and NCV parameters did not significantly differ from the normative data before the start of therapy, and against the background of treatment with onasemnogen abeparvovek, an increase in the CMAP and NCV amplitude of the was noted with increasing age in patients. The amplitude of the CMAP and NCV before treatment were 5.00 mV (4.30–5.30), min — 1.40, max — 8.00 and 33.60 m/s (32.40–38.10), min — 27.40, max — 48.90, and at the age of 13 to 24 months — 6.25 mV (5.20–6.85), min — 4.70, max — 7.80 and 55.20 m/s (52.80–57.60), min — 49.10, max — 60.30, respectively. All SMA type I patients showed a significant decrease in the amplitude of the M-response both before therapy and during 2-year follow-up after the start of treatment. The amplitude of the CMAP and NCV before treatment were 0.28 mV (0.13–0.65), min — 0.05, max — 2.20 and 31.90 m/s (27.50–35.90), min — 22.30, max — 52.00, and at the age of 13 to 24 months — 0.70 mV (0.46–1.15), min — 0.17, max — 4.60 and 48.40 m/s (43.95–50.98), min — 38.90, max — 56.10, respectively.

Conclusion. When comparing the MNCV parameters in presymptomatic with SMA type I patients, significant differences were shown, which were manifested in symptomatic patients with a low amplitude of the CMAP and reduced values of NCV both before therapy and during 2-year follow-up after treatment with onasemnogen abeparvovek. Thus, conducting MNCV in children with SMA is an easily feasible study, and evaluating the amplitude of the CMAP makes it possible to reliably, albeit indirectly, verify degeneration of spinal cord motor neurons in symptomatic patients against the background of pathogenetic treatment.

Compliance with ethical standards. Permission was obtained from the local ethics committee of the National Medical Research Center for Children’s Health to conduct this study Minutes of the meeting of the local ethics committee from October 06, 2022, No. 10.

Contribution:
Fisenko D.A. — concept and design of the review, writing the text, editing;
Kurenkov A.L. — concept and design of the review, writing the text, editing;
Kuzenkova L.M. — concept and design of the review, editing;
Chernikov V.V. — statistical data processing;
Uvakina E.V. — concept and design of the review, editing;
Popovich S.G. — editing;
Bursagova B.I. — editing;
Belousova T.N. — editing;
Kniazeva N.Y. — editing;
Novikov M.Y. — editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: November 14, 2024
Accepted: November 29, 2024
Published: January 31, 2025

Introduction. In 2025, we will commemorate the 100^th anniversary of the first pediatric case of Guillain–Barré Syndrome (GBS), initially documented by M. Monnier-Vinard. This significant milestone invites a reevaluation of our contemporary understanding of GBS in children. While the original description of GBS was thorough, the categorization has expanded over time to include a wider array of conditions, resulting in the term applied to various acute demyelinating polyneuropathies. The atypical forms of GBS present notable diagnostic challenges for healthcare providers.

Objective. To analyze the demographic and clinical characteristics, treatment methods, and prognosis of GBS in children in Russia.

Materials and methods. The study included fifty 6 months – 15 years patients with typical and atypical forms of Guillain-Barré syndrome (GBS). Neurological status was assessed using the Medical Research Council sum score and the Hughes disability scale. Additionally, data from cerebrospinal fluid analysis, nerve conduction study, magnetic resonance imaging of the spine, and peripheral nerves ultrasound was evaluated.

Results. The classic ascending subtype of GBS was diagnosed in 30 (60%) patients, while atypical manifestations were observed in 17 (34%). Three (6%) patients had an overlap syndrome: GBS with acute myelitis. The median age of the patients was 7 [5.0; 11.0] years. Two peaks of GBS incidence associated with respiratory and gastrointestinal infections were identified. The most common initial symptoms were pain (80%), weakness in the legs (64%), and difficulty walking (54%). All 26 (100%) GBS patients were followed for 12 months from the onset of the disease regained the ability to walk.

Conclusion. Both typical and atypical forms of GBS can occur in children. Overlap syndrome (GBS with acute myelitis) is a rare complication following COVID-19 and may go undiagnosed. With appropriate therapy the prognosis for both typical and atypical forms of GBS is generally favourable.

Compliance with ethical standards. The study was conducted as part of the research project “Dysimmune Polyneuropathies in Children: Clinical and Diagnostic Features and Prognosis,” approved by the Ethics Committee (Protocol No. 192 dated January 27, 2020) of the Pirogov Russian National Research Medical University.

Contribution:
Kozyreva A.A. — concept, research design, research coordination, material collection and data processing, review of publications on the topic, text writing, article editing;
Bembeeva R.Ts. — concept, research design, text writing, article editing;
Druzhinina E.S. — text writing, article editing, peripheral nerve ultrasound and nerve conduction studies;
Shakaryan А.К. — material collection, article editing;
Guseva G.D. — material collection, article editing;
Besedin S.G. — material collection, article editing;
Zavadenko N.N. — concept, research design, research coordination, article editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: November 1, 2024
Accepted: November 11, 2024
Published: January 31, 2025

Merosin-deficient muscular dystrophy is a rare neuromuscular disease characterized by diffuse muscular and epileptic seizures. The disease is inherited in an autosomal recessive type and occurs as a result of biallelic variants in the LAMA2 gene. In this gene there are described all types of violations of the normal nucleotide sequence (single nucleotide variants, variations in the number of DNA copies) which can lead to difficulties in genetic search. The combination of phenotype features (hypomimia, elongated face, ophthalmoparesis, muscle hypotonia, and weakness, spinal rigidity, contractures of large joints), laboratory and instrumental research results (increased activity of creatinephosphokinase in the blood, leukopathy on brain MRI) will help you choose the right diagnostic search tactics. In this article, we present a clinical case of a patient with three identified variants in the LAMA2 gene: two point substitutions (c.4048C>T and c.4860+75G>C) and deletion of exons 2 and 3. The use of several methods of genetic testing (high-throughput sequencing, chromosomal microarray analysis, Sanger sequencing) allowed the establishing of the diagnosis, which subsequently led to successful prenatal diagnosis and the birth of healthy siblings.

Contribution:
Monakhova A.V. — writing text;
Vlodavets D.V. — concept, editing;
Kanivets I.V. — editing.
All co-authors — approval of the final version of the manuscript, responsibility for the integrity of all parts of the manuscript.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: November 13, 2024
Accepted: November 11, 2024
Published: January 31, 2024

L-aromatic amino acid decarboxylase deficiency (AADC) is a rare autosomal recessive neurometabolic disease characterized by impaired biosynthesis of neurotransmitters and manifested by disorders of movement and autonomic regulation.In the article there is discussed the diagnostic path and treatment options for a 7-year patient with severe AADC deficiency. Combination of severe neurological disorders (muscular hypotension, dystonia, hyperkinesis, oculogyric crises) and autonomic disorders (increased sweating, hypersalivation, thermoregulation disorders, nasal congestion, dyspepsia, etc.) is clearly demonstrated to require the detection of 3-O-methyldopa in dried blood spots to exclude AADC deficiency. Given the emergence of gene therapy, which is available to patients with a confirmed diagnosis of AADC deficiency in Russia within the criteria of the Circle of Kindness Foundation, it is necessary to popularize information about L-aromatic amino acid decarboxylase deficiency in the general medical community, to improve the prognosis and quality of life in AADC patients.

Contribution:
Uvakina E.V. — concept and design of the study, writing the text, editing;
Kuzenkova L.M. — concept and design of the study, writing the text, editing;
Gukosyan D.I. — concept and design of the study, writing the text, editing;
Popovich S.G. — editing;
Podkletnova T.V. — editing;
Lyalina A.A. — editing;
Pushkov A.A. — editing;
Savostyanov K.V. — editing;
Kurova Y.A. — editing;
Nikolenko D.S. — editing.
All co-authors are responsible for the integrity of all parts of the manuscript and approval of its final version.

Acknowledgements. The study had no sponsorship.

Conflict of interest. The authors declare no conflict of interest.

Received: December 17, 2024
Accepted: January 10, 2025
Published: January 31, 2025