Late diagnosis of Gitelman syndrome in an elderly patient: identification of a novel SLC12A3 pathogenic variant

Gitelman syndrome (GS) is an inherited salt-wasting, hypokalemic tubulopathy caused mainly by biallelic loss-of-function variants in the SLC12A3 gene. Despite being classically diagnosed in adolescence, delayed recognition may occur. We present the case of a 74-year-old man with a history of hypokalemia, in whom the diagnostic evaluation revealed hypokalemia, hypomagnesemia, metabolic alkalosis, hypocalciuria, and secondary hyperreninemic hyperaldosteronism, consistent with renal potassium wasting. Given the late presentation, the main challenge was the need to distinguish an inherited tubulopathy from common acquired causes of hypokalemia. Genetic testing was performed, identifying a previously unreported homozygous out-of-frame deletion in exon 25 of the SLC12A3 gene, predicted to result in loss of protein function and therefore to be pathogenic. Treatment with supplementation plus spironolactone achieved sustained biochemical improvement and clinical stability during long-term follow-up. This case highlights that GS should be considered in patients with chronic unexplained hypokalemia regardless of age, and that genetic testing is essential for definitive diagnosis.