Gitelman's Syndrome: From Clinic to Gene

Shih-Hua Lin

《Acta Nephrologica》 17卷3期 (2003/10) Pp. 113-120

並列摘要

Gitelman's syndrome (GS) is an inherited or acquired renal tubular disorder characterized by hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. The electrolyte disturbances resemble those observed in chronic administration of thiazide diuretics. Patients with GS usually present the clinical symptoms during childhood or adolescence. Salt craving, nocturia, muscle weakness, tetanic episodes, paresthesias, and paralysis are the most common cardinal symptoms. Several extrarenal and renal disorders with similar laboratory findings and clinical presentations may be misdiagnosed as GS. Urine sodium (Na(superscript +)), chloride (Clˉ), and urine calcium to creatinine ratio (mmol/mmol) in the concentrated urine are very helpful in diagnosing GS. Although a minority of GS patients has mutations in the basolateral chloride channels (CLCNKB), the majority of GS results from inactivating mutations to the SLC12A3 gene, which encodes the thiazide-sensitive sodium chloride (NaCl) cotransporter (NCC) on the apical membrane of distal convoluted tubule cells. To date, more than 100 distinct NCC mutations have been reported. Functional expression of these NCC mutations in X. laevis oocytes or polarized epithelial cells revealed that misrouting of the mutant NCC is mainly responsible for defective NaCl reabsorption in GS. Gene therapy will be the future treatment for GS, like other inherited electrolyte and water disorders.

並列關鍵字

Chloride channel ； Gitelman's syndrome ； hypokalemia ； hypomagnesemia ； hypocalciuria ； metabolic alkalosis ； mutation ； sodium chloride cotransporter