Abstract: PUB114
A Novel SLC12A3 Pathogenic Variant Causing Gitelman Syndrome
Session Information
Category: Fluid, Electrolytes, and Acid-Base Disorders
- 1102 Fluid, Electrolyte, and Acid-Base Disorders: Clinical
Authors
- Khan, Ursel, The University of Texas Medical Branch at Galveston Department of Internal Medicine, Galveston, Texas, United States
- Munir, Daaniyal Dawood, The University of Texas Medical Branch at Galveston Department of Internal Medicine, Galveston, Texas, United States
- Mchenry, James, The University of Texas Medical Branch at Galveston Department of Internal Medicine, Galveston, Texas, United States
Introduction
Gitelman syndrome is a rare autosomal recessive renal tubular disorder caused by mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter of the distal convoluted tubule. Impaired sodium chloride reabsorption results in renal salt wasting, secondary activation of the renin-angiotensin-aldosterone system, and characteristic electrolyte abnormalities including hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria. Patients will present with fatigue, weakness, cramps, palpitations, thirst, or polyuria, but, diagnosis is often delayed because symptoms may be subtle or nonspecific. Genetic testing plays an important role in confirming the diagnosis and expanding the known mutational spectrum associated with the disease.
Case Description
A 34-year-old male with a history of acne vulgaris was admitted for evaluation of persistent hypokalemia that had progressively worsened over one month despite daily oral potassium supplementation. Initial evaluation demonstrated hypokalemia and hypomagnesemia with metabolic alkalosis. Further workup revealed renal potassium wasting, hypocalciuria, low-normal blood pressure, and chronic thirst, raising concern for Gitelman syndrome. Magnesium and potassium repletion were continued throughout hospitalization. Patient was started on amiloride and magnesium gluconate, with subsequent up-titration of amiloride because of persistent electrolyte abnormalities. Renin and aldosterone testing showed no evidence of primary hyperaldosteronism. Genetic testing for Gitelman syndrome was sent to an outside laboratory. The patient was ultimately found to have a previously unreported homozygous frameshift variant, NM_000339.2:c.2836_2837insCTCAGGC (p.Cys946Serfs*10), in SLC12A3, classified as likely pathogenic.
Discussion
This case highlights the importance of considering inherited renal tubular disorders in adults with persistent hypokalemic metabolic alkalosis and renal potassium wasting. The combination of hypokalemia, hypomagnesemia, hypocalciuria, and low-normal blood pressure strongly supported the diagnosis of Gitelman syndrome and helped distinguish it from other etiologies. Furthermore, this case expands the known mutational spectrum of SLC12A3 and demonstrates how strong genotype-phenotype correlation can support pathogenic classification of previously unreported variants.