A Clinical Roadmap to Managing a Patient with Gitelman Syndrome

Introduction: Gitelman syndrome is a salt wasting tubulopathy whereby the classic findings are hypokalemia, metabolic alkalosis, hypomagnesemia and hypocalciuria. The cause is an inactivating mutation in the SLC12A3 gene which encodes the thiazide sensitive sodium-chloride cotransporter on the apical membrane of the distal convulted tubule. There is significant variability in the phenotypic manifestatons of the disease. In any case, management includes liberal salt intake and supplementation of potassium and magnesium as the hallmarks. However, literature providing specific guidance and dosing in this arena is lacking. Case Description: 44 year old male initially presented to the ER with palpitations and near syncope. He was found to have a serum potassium of 2.3 mmol/L and serum magnesium of 1.2 mg/dL. Both were supplemented intravenously and he was discharged with outpatient follow up. Renal magnesium loss was confirmed with 24 hour urine magnesium of 220 mg and fractional excretion of magnesium of 11%. Urine calcium was low at 60 mg per day. Genetic testing was pursued given the high suspicion for Gitelman syndrome, revealing compound heterozygous mutations in SLC12A3. As his electrolytes were in disarray and blood pressure low (~90/50 mm Hg) a treatment regimen was sought. The goal being a strategy that would be both effective, well tolerated and safe. Discussion: Specific management of Gitelman syndrome with a prevalence of only 1-10 per 40,000 is not precisely outlined or defined. Much additional information is needed to understand the appropriate options, as supportive evidence is lacking. In this particular case, we settled upon the following: potassium chloride 40 mEq per day, magnesium chloride to provide 640 mg elemental magnesium per day, and sodium chloride tablets 2 grams three times per day. Adjustements were made along the way to arrive at an overall stable electrolyte panel. On a recent visit, BP measured 116/80 mm Hg with serum magnesium 1.4 mg/dL and potassium 3.7 mmol/L. He has not had any additional hospitalizations for related metabolic disturbances. Future practice may be guided by this framework with the realization that goal electrolyte values may be lower than the expected range. Long term outcomes in such patients are also potential areas for further investigation.