engleski

BARTTER SYNDROME- STILL A DIAGNOSTIC CHALLENGE

Introduction: Bartter syndrome is an inherited tubulopathy that presents in infancy or childhood with metabolic alkalosis, hypokalemia and normal blood pressure. There are 4 types of Bartter syndrome, with types I, II and IV being more severe, and type III (classic form) being a milder form with a variable presentation, sometimes mimicking other tubulopathies. Therefore, Bartter syndrome should be a permanent differential diagnosis in children with various tublopathies. Material and methods: Case report. Results: We report a case of a 10-year-old boy who was followed by a pediatric nephrologyst from infancy because of incomplete diabetes insipidus. During that time his electrolytes and blood pressure were normal. At the age of 7 hypercalciuria and hyperreninemia were noted for the first time, as well as hyperparathyroidism and osteopenia. Serial renal ultrasounds were normal. Later on, hypokalemia was also noted. His diagnose was then subjected to reevaluation. Because of severe hypercalciuria, CT urography was done and revealed multiple urolites. Genetic analysis was then finally preformed (Blueprint Nephrolitiasis panel with 35 genes) identifying a novel hemizygous frameshift variant c.38_59delinsAGTCAC, p. (Gly13Glufs*22) and a heterozygous deletion chr1:g.16351202_16372237del which encompasses exons of both CLCNKB and CLCKNA genes. The diagnosis of Bartter syndrome was thereby confirmed. Conclusions: Type III Bartter syndrome (classic Bartter syndrome) has a very variable presentation, sometimes overlapping with other tubulopathies. It is caused by loss-of-function mutations in CLCNKB gene encoding the voltage- gated chloride channel CICKb, which is expressed in the thick ascending limb of the loop of Henli, but also in the distal convulated tubule, possibly explaining the variable features. While recognizing atypical presentations is still the first step towards the correct diagnosis, modern targeted clinical panels ease the way. Discovering novel mutations is important because of better understanding of molecular mechanisms as well as targeted treatment for the individual patient.

Bartter syndrome ; tubulopathy ; differential diagnosis ; children

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