Phenotypical heterogeneity of Bartter syndrome

Background: Bartter's syndrome (hypokalemic hypochloremic metabolic alkalosis) is a very rare autosomal recessive salt-losing tubulopathy caused by a defect in sodium and chloride reabsorption in the thick ascending limb of Henle's loop and distal convoluted tubules. Recently, it has become apparent that the clinical classification of Bartter's syndrome does not always match to the clinical symptoms associated with its gene-specific type. So, the most common genetic type 3 reveals phenotypic variety with a clinical course of not only classical, but also antenatal / neonatal Bartter's syndrome or Gitelman-like syndrome. The aim of our study was to investigate the phenotypic and genotypic variability of Bartter's syndrome, as well as the relationship of the phenotype and genotype with the efficacy of therapy and outcomes in children. Materials and methods: the group of 7 children (median age of disease onset 0.1 years, median diagnosis 3.0 years) from unrelated marriages with clinically established Bartter syndrome. Arterial hypertension and hearing loss were absent in all patients included in the study. Results: 5 (72%) of 7 patients were diagnosed with Bartter syndrome type 3 (causative variants in the CLCNKB gene) using molecular genetic analysis, 1 (14%) - type 2 (causative variants in the KCNJ1 gene), and for one child a study not completed. Correlations between the type of mutations and the phenotype were not revealed in the group of patients with genetic type 3, possibly due to a small number of patients. Two patients with type 3 Bartter's syndrome and missense mutations in the CLCNKB gene showed progression to stage 4 chronic kidney disease, 6 years later and 15.5 years after the onset of the disease. Continuous therapy with indomethacin was received by 3 children, potassium chloride - 7 patients. All children achieved stable compensation of water-electrolyte disturbances, acid-base balance. Conclusion: Bartter's syndrome type 3, represented by mutations in the CLCNKB gene, is the prevailing genetic variant and reveals a great phenotypic heterogeneity, which confirm the need for molecular genetic study of patients, including those with an already confirmed clinical diagnosis.

cиндром Барттера тип 3, cиндром Барттера тип 2, ген CLCNKB, ген KCNJ1, нестероидные противовоспалительные агенты, дети, Bartter syndrome type 3, Bartter syndrome type 2, CLCNKB gene, KCNJ1 gene, non-steroidal anti-inflammatory drugs, children

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