GitelmanSyndrom

Gitelman syndrome, sometimes written in German as Gitelman-Syndrom (GitelmanSyndrom in English contexts), is a rare inherited kidney disorder characterized by electrolyte abnormalities including hypokalemia, hypomagnesemia, metabolic alkalosis, and hypocalciuria. It is caused by biallelic mutations in the SLC12A3 gene, which encodes the thiazide-sensitive Na-Cl cotransporter NCC in the distal convoluted tubule. The condition is inherited in an autosomal recessive pattern.

Pathophysiology involves reduced reabsorption of sodium and chloride in the distal tubule due to NCC dysfunction. This leads to mild chronic salt wasting and volume depletion, with activation of the renin-angiotensin-aldosterone system. Aldosterone promotes potassium and hydrogen ion loss, causing hypokalemic metabolic alkalosis. Hypomagnesemia results from impaired magnesium handling in the distal tubule, and hypocalciuria occurs because calcium reabsorption is enhanced.

Clinically, most individuals present in adolescence or adulthood with fatigue, muscle cramps, weakness, and sometimes paresthesias. Polyuria and polydipsia may occur due to nephrogenic effects of the electrolyte disturbances. Blood pressure is typically normal or low. Some patients report salt cravings or exercise-related symptoms.

Diagnosis relies on the combination of biochemical findings—low serum potassium and magnesium, metabolic alkalosis, elevated plasma renin and aldosterone levels, and low urinary calcium excretion—and confirmation by genetic testing for SLC12A3 mutations.

Management focuses on lifelong electrolyte replacement and correction of volume status. Oral magnesium supplementation is usually required to correct hypomagnesemia, along with potassium supplements as needed and adequate salt intake. Some individuals may benefit from potassium-sparing diuretics or other supportive therapies. Regular monitoring for electrolyte balance and potential cardiac arrhythmias is advised; prognosis is generally favorable with appropriate treatment, though symptoms persist lifelong.