Gitelman Syndrome in the Sixth Decade: An Atypical Presentation with Severe Electrolyte Abnormalities and Genetic Heterogeneity

Gitelman syndrome (GS) is a rare autosomal recessive salt-losing tubulopathy characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. While typically presenting in adolescence or early adulthood, atypical presentations and delayed diagnoses into later adulthood pose significant clinical challenges. We report a case of a 60-year-old female who presented with generalized weakness, lethargy, and severe electrolyte abnormalities, including profound hyponatremia (109 mmol/L), hypokalemia (2.91 mmol/L), hypocalcemia (<6.0 mg/dL), and hypomagnesemia (0.6 mg/dL). Laboratory investigations revealed metabolic alkalosis, hypochloremia, elevated parathyroid hormone (172.90 pg/ml), and inappropriate renal potassium wasting. Urinary studies showed relative hypocalciuria in the context of severe hypocalcemia. Genetic testing revealed no pathogenic variants in the SLC12A3 gene typically associated with GS, though variants of uncertain significance were identified in SLC22A12 and VPS33B genes. Management included aggressive electrolyte replacement, spironolactone, and dietary modifications, resulting in clinical improvement despite incomplete normalization of electrolytes. This case illustrates the complex clinical spectrum of GS, highlighting the importance of considering this diagnosis in older adults with unexplained electrolyte abnormalities. The absence of confirmatory SLC12A3 mutations despite classic biochemical features supports emerging evidence of genetic heterogeneity in GS. This case emphasizes the value of clinical diagnosis when genetic confirmation is lacking and the effectiveness of targeted symptomatic management. GS should be considered in the differential diagnosis of electrolyte abnormalities across all age groups. A high index of clinical suspicion and characteristic biochemical profile can guide diagnosis and management even in the absence of confirmatory genetic findings.