Gitelman syndrome: an analysis of the underlying pathophysiologic mechanisms of acid–base and electrolyte abnormalities

Gitelman syndrome is the most common inherited tubular disease resulting from mutations of the SLC12A3 gene that encodes the thiazide-sensitive sodium–chloride cotransporter in the early distal convoluted tubules. The review presents the underlying pathophysiologic mechanisms of acid–base and electrolyte abnormalities observed in patients with Gitelman syndrome. The syndrome is usually characterized by hypokalemic metabolic alkalosis in combination with hypomagnesemia and hypocalciuria. Additionally, increased chloride excretion and renin/aldosterone levels, hypophosphatemia (occasionally), hyponatremia (rarely) and glucose intolerance/insulin resistance have been reported. The knowledge of the pathophysiologic mechanisms is useful for the treatment of patients with Gitelman syndrome as well as for the understanding of other tubular diseases.