Gitelman syndrome and Bartter syndrome are hereditary hypokalemic tubulopathies (tubular salt-wasting disorders) with distinct phenotypic features. Gitelman syndrome is an autosomal recessive disorder characterized by hypokalemia, metabolic alkalosis, hypomagnesemia, and hypocalciuria.

Clinically, patients with Gitelman syndrome usually present with symptoms during childhood or adolescence. Salt craving, nocturia, muscle weakness to paralysis, titanic episodes, and paresthesias have been reported as the most frequent cardinal symptoms, related to hypokalemia and/or hypomagnesemia.

To date, more than 100 distinct mutations in the thiazide-sensitive NaCl cotransporter (SLC12A3) gene have been reported to cause Gitelman syndrome. SLC12A3 maps to chromosome 16q13 and contains 26 exons. SLC12A3 encodes the thiazide-sensitive NaCl cotransporter that has a predicted protein sequence of 1,021 amino acids (112 kD) and shows a structure common to other members of the Na-K-Cl cotransporter family: a central region harboring 12 transmembrane domains and the 2 intracellular hydrophilic amino and carboxyl termini. Thiazide-sensitive NaCl cotransporter is a renal protein expressed in the distal convoluted tubule and plays a critical role in regulating the salt/water balance and blood pressure.