Adult-Onset Classic Bartter Syndrome Type 3 with Polycythemia: Rare Presentation in Siblings with Eight-Year Follow-Up

Introduction: Bartter syndrome(BS) is a rare autosomal recessive renal tubular disorder characterized by hypokalemia, metabolic alkalosis, and hypercalciuria with low to normal blood pressure. Based on genetic mutations, BS is classified into five types. Types 1, 2, 4a, and 4b typically present in infancy. Type 3, or classical BS, presents often during adolescence, and tends to be milder. We present a rare case of adult-onset Type 3 BS with two heterozygous CLCNKB variants requiring unusually high potassium supplementation and associated with polycythemia in both affected siblings. Case Description: An 18-year-old Caucasian male presented with recurrent lower limb weakness after exertion, requiring multiple ED visits. He denied GI losses, diuretic, laxative, or licorice use, and had no relevant family history. Blood pressure was normal. Labs showed hypokalemia, metabolic alkalosis, and normal magnesium. Further workup revealed hypercalciuria, hyperkaliuria, elevated renin, and normal aldosterone, ACTH, and cortisol. Imaging ruled out adrenal, pituitary, and renovascular pathology. Genetic testing identified a hemizygous CLCNKB pathogenic variant (c.1693del, p.Glu565Argfs*7) and a heterozygous whole-gene deletion, confirming Type 3 BS. He required 830–850 mEq/day of oral potassium in addition to eplerenone. He did not tolerate spironolactone, amiloride and indomethacin due to their side effects. His younger sister by 3 years presented with similar symptoms and shared the same genetic findings. Notably, both siblings had polycythemia with normal erythropoietin. Discussion: Type 3 BS is caused by mutations in CLCNKB, leading to defective ClC-Kb channels and salt-wasting nephropathy. Differentiation from Gitelman syndrome is made by genetic testing and clinically, as the latter involves SLC12A3 mutations, and presents with hypocalciuria and hypomagnesemia. Despite heterozygosity, our patient had high potassium needs, which is typically seen in homozygous cases. Polycythemia is extremely rare in BS. The mechanism is unclear but may involve chronic RAAS stimulation or juxtaglomerular hyperplasia. This case highlights the importance of genetic testing, tailored treatment, and awareness of rare associations like polycythemia in BS. Lifelong follow-up is crucial due to the risks of CKD and nephrocalcinosis.