Gitelman syndrome

Gitelman syndrome (GS), also known as familial hypokalemia-hypomagnesemia, is a rare inherited salt-losing tubulopathy affecting the kidneys. It is caused by biallelic loss-of-function mutations in the SLC12A3 gene, which encodes the thiazide-sensitive sodium-chloride cotransporter (NCC) located in the distal convoluted tubule of the kidney. This defect impairs the kidney's ability to reabsorb sodium and chloride, leading to a characteristic set of electrolyte abnormalities including hypokalemia (low potassium), hypomagnesemia (low magnesium), hypocalciuria (low urinary calcium), and metabolic alkalosis. The condition mimics the biochemical effects of chronic thiazide diuretic use. Gitelman syndrome typically presents in late childhood, adolescence, or adulthood, though it can occasionally be identified earlier. Common symptoms include muscle cramps, muscle weakness, fatigue, dizziness, salt craving, episodes of tetany (involuntary muscle contractions often related to low magnesium), and paresthesias (tingling sensations). Some patients experience cardiac symptoms such as palpitations, and prolongation of the QT interval on electrocardiogram can occur due to electrolyte disturbances, which in rare cases may predispose to cardiac arrhythmias. Joint symptoms, including chondrocalcinosis (calcium deposits in cartilage), have been reported in some adults. Many patients have a relatively mild clinical course, and some individuals may be asymptomatic or only mildly affected, though quality of life can be significantly impaired in others. Treatment of Gitelman syndrome is primarily supportive and focuses on lifelong oral supplementation of potassium and magnesium. Magnesium supplementation (preferably magnesium chloride) is a cornerstone of therapy, as correcting magnesium levels can also help improve potassium levels. Potassium-sparing diuretics such as amiloride or spironolactone may be used as adjunctive therapy. A liberal salt intake is generally encouraged. Patients require regular monitoring of electrolytes and renal function. With appropriate management, the long-term prognosis is generally favorable, and the condition is not typically associated with progressive chronic kidney disease.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Gitelman syndrome