Gitelman Syndrome With Two Variants of Uncertain Significance: A Case Report

Gitelman syndrome (GS) is an autosomal recessive salt-wasting tubulopathy caused by pathogenic variants in SLC12A3, characterized by renal potassium wasting, hypokalemic metabolic alkalosis, hypomagnesemia, and typically low urinary calcium excretion. We report the case of a 47-year-old woman with recurrent hypokalemia and episodes of asthenia, myalgias, and generalized muscle weakness. She denied gastrointestinal losses and diuretic or laxative use, and examination showed normal blood pressure. Electrocardiography revealed sinus rhythm without QT prolongation, and renal ultrasonography showed no structural abnormalities or nephrocalcinosis. Laboratory evaluation confirmed mild hypokalemia with metabolic alkalosis, preserved renal function, and hypomagnesemia. Urinary studies demonstrated renal potassium wasting with increased magnesium excretion and low urinary calcium excretion. Targeted next-generation sequencing identified two heterozygous SLC12A3 missense variants of uncertain significance (VUS) (NM_000339.3:c.505G>A, p.Val169Ile; NM_000339.3:c.1452C>G, p.Cys484Trp), and segregation analysis confirmed an in-trans configuration consistent with compound heterozygosity, supporting the diagnosis in the context of a classic biochemical phenotype. She was managed with oral potassium chloride supplementation. Spironolactone was discontinued due to symptomatic hypotension, and she remains clinically stable on follow-up. This case emphasizes the value of integrating biochemical findings with segregation analysis when only VUS are identified and highlights the need for individualized long-term management and genetic counseling in GS.