Which salt wasting tubulopathy represents the mirror image of PHA 2?
Individuals affected by Gitelman syndrome present with symptoms identical to those who are on thiazide diuretics; the features of this condition mirror the findings in PHA 2 with the exception of hypomagnesemia and include hypochloremic metabolic alkalosis, hypokalemia, and hypocalciuria. Affected individuals are typically asymptomatic; however, muscular cramps, weakness/fatigue, and irritability have been described. More severe symptoms, such as tetany and paralysis, are rare.
The condition is caused by homozygous or compound heterozygous loss-of-function mutations in SLC12A3 encoding the NCCT, inactivating NCCT expression in the apical membrane of DCT epithelia, thereby causing urinary sodium wasting. Individuals with heterozygous loss-of-function mutations in NCCT may have a survival benefit due to a lower blood pressure level and increased bone mineral density.
