Schimke immuno-osseous dysplasia (SIOD) is a hereditary autosomal-recessive multi-system disorder with early mortality. It has variable clinical presentations, mainly characterised by disproportional short stature, steroid-resistant nephrotic syndrome, spondyloepiphyseal dysplasia, and T-cell immunodeficiency. In the majority of cases, SIOD is caused by pathogenic sequence variants (PSVs) in the SMARCAL1 gene that encodes protein involved in chromatin remodelling. SIOD is an ultra-rare condition, with an incidence of ~1 per 1–3 million live births; data on its genetic and clinical features are scarce. We conducted a retrospective study of 21 paediatric patients with SIOD diagnosed in our centre during the years 2003–2023. The most common extra-renal clinical features were short stature, osseous dysplasia, multiple stigmas, and leukopenia. Proteinuria of varying severity was observed in 16 cases. The five-year overall survival rate (OS) was 89% (95% CI 77–100%), and the ten-year OS was 10%. Next-generation sequencing (NGS) revealed the following PSVs in SMARCAL1 in 19 patients: c.355_500del, c.2542G>T, c.2290C>T, c.2562del, c.2533_2534del, c.1582A>C, c.1933C>T, c.1010T>C, c.1736C>T, c.2070dup, c.2551A>T, c.2149_2150dup, c.939delC, and c.1451T>A; the most common was c.2542G>T, resulting in premature translation termination (p.E848*), and it was found in 14 patients either in a homozygous (four patients) or compound-heterozygous (10 patients) state. According to microsatellite analysis, it is a “founder mutation” in Russia.

Introduction. Nephrocalcinosis (NC) is defined as the deposition of calcium oxalate or calcium phosphate in the intratubular lumen and/or kidney interstitium. Recent studies have reported that NC might be a specific sign of hereditary kidney diseases with various phenotypic manifestations. The rate of genetic mutation as a rule was higher in children with earlier onset and positive family history. Purpose. To study the causes, characterize the genotype and phenotype in Russian children with NC. Materials and methods. A single-center retrospective-prospective cohort study included 91 patient under the age of 18 years, 57 (62.6%) boys and 34 (37.4%) girls with bilateral NC. We analyzed the phenotype and kidney function in NC children classified into 3 groups according to etiology: 1) primary tubulopathies; 2) tubulopathies due to metabolic and endocrine disorders; 3) NC, unconfirmed by molecular genetic research. Results. Pathogenic nucleotide variants were identified in 51 (56%) children with a predominance in the genes CLCN5, CYP24A1, AGXT, HPRT1 described in patients with Dent disease (OMIM 300009), primary hyperoxaluria type 1 (OMIM 259900), idiopathic infantile hypercalcemia type 1 (OMIM 143880), Lesh–Nihan syndrome (OMIM 300322) respectively. The median age of detection of NC was 16 years, 4 [3.9; 52.2 months, among which 42 (46.1%) children were under the age of 1 year, 44 (48.4%) aged 1 to 10 years, 5 (5.5%) older than 10 years. Various bone deformities prevailed among the extrarenal manifestations (19 (20.4%)). Over 3 years of follow-up (n = 51) the average GFR changed from 102.5 ± 26.0 ml/min/1.73 m2 to 94.5 ± 21.9 ml/min/1.73 m2 (p = 0.002); over 5 years of follow-up (n = 31) from 104.7 ± 23.9 ml/min/1.73 m2 to 89.6 ± 25.1 ml/min/1.73 m2 (p = 0.002), that was statistically significant in the group of primary tubulopathies (p = 0.030; p = 0.002). At baseline, the average GFR value was lower in NC stages 2 and 3. Conclusion. Conducting a molecular genetic study in NC children, in addition to early diagnosis of diseases with variable renal prognosis and will also help to achieve effectiveness in the timely prescription of pathogenetic and symptomatic therapy.

Роль медицинской сестры в проведении перитонеального диализа при хронической почечной недостаточности у детей

Introduction. Nephrotic syndrome (NS) with an onset in the first year of life is one of the actual problems in pediatric nephrology due to the limited therapeutic options, the ineffectiveness of immunosuppressive therapy, and inevitable progression to chronic kidney disease (CKD). The basis of congenital NS (CNS) and infantile NS (INS) is a genetically determined pathology of podocytes. The timely verification of such pathology allows avoiding ineffective therapy and helps to predict outcomes. Aim. To determine CNS and INS’s clinical and molecular genetic characteristics in Russian children. Materials and methods. This study performed molecular genetic testing of 99 children with an early onset of NS. Results. In children with CNS and INS, the genetic cause of the disease was verified in 85%. Causative nucleotide variants prevailed in the NPHS1, NPHS2, WT1 genes. It became possible to identify the significant nucleotide variants for the Russian group of children. Children with NS at an early age turned out to be resistant to therapy with calcineurin inhibitors, which should be considered when choosing therapy tactics. Conclusion. We detected the genetic structure of congenital and infantile NS in the Russian Federation during the study. We analyzed the effectiveness of therapy with calcineurin inhibitors and the rate of CKD progression in this group.

Introduction. Nephropathic cystinosis (NC) is an extremely rare hereditary disease characterized by the intralysosomal accumulation of cystine crystals caused by mutations in the CTNS gene. NC is the most common cause of Fanconi syndrome in children, which has a poor prognosis without continued pathogenetic therapy, mainly affecting renal function. The aim of the work is to determine the features of the clinical course of NC, the experience of diagnosis and treatment in a multidisciplinary hospital of the federal center. Materials and methods. The retrospective study included 37 NC patients (19 girls, 18 boys) for the period from 2008 to 2024. Results. Manifestations of Fanconi syndrome were noted in all patients; the age of verification of symptoms ranged from 2 to 119 months, the median was 7 [6; 14] months. At the time of diagnosis at the age 8 to 294 months, median 27 [19; 71] months, in 17 (46%) children documented a decrease in eGFR < 60 ml/min/1.73 m2. An extended deletion of 57 thousand pairs of nucleotides was detected in 17 (46%) patients. Renal replacement therapy was initiated in 24 (65%) patients, median age 8.7 [7.7; 11.9] years. Kidney transplantation was performed in 21 patients, median age was 10.2 years (8.8; 13.0), there were no cases of loss of allograft. Pathogenetic cysteamine therapy was initiated in 36 (97.3%) children, range 8 to 174 months, median 33 [23; 82] months, was achieved a decrease the concentration of cystine leukocytes and a decrease in the frequency of extrarenal complications. There were a significant slowdown in the rate of decrease in renal function to CKD stage 3 and stage 5 with early initiation of cysteamine bitatrate and subsequent adherence to therapy. Conclusion. Nephropathic cystinosis is an important problem in Pediatrics due to the extremely late diagnosis and lack of alertness of primary care specialists. Early initiation of supportive and pathogenetic therapy allows improving the condition and development of patients, as well as slowdown the rate of decrease in renal function and extrarenal damage.