A 32-year-old woman reports lifelong intermittent muscle cramps and episodes of weakness. BP is 108/70 mmHg. Labs: K 2.6 mEq/L, Mg 1.2 mg/dL, HCO3 30 mEq/L, renin elevated, aldosterone elevated. Twenty-four hour urine calcium excretion is 40 mg/day (low). Which transporter defect explains these findings?
- A Loss-of-function mutation of the thiazide-sensitive sodium chloride cotransporter in the distal convoluted tubule ✓
- B Loss-of-function mutation of the sodium potassium two chloride cotransporter in the thick ascending limb
- C Gain-of-function mutation of the epithelial sodium channel in the collecting duct
- D Defect in the chloride channel CLCNKB of the thick ascending limb
Explanation
Gitelman syndrome is caused by inactivating mutations of SLC12A3, the thiazide-sensitive NaCl cotransporter of the distal convoluted tubule. It mimics chronic thiazide ingestion: hypokalaemic metabolic alkalosis, hypomagnesaemia, hypocalciuria, normal or low blood pressure, and secondary hyperreninaemic hyperaldosteronism. It usually presents in adolescence or adulthood with cramps. Options B and D describe Bartter variants, which present in early childhood with hypercalciuria and sometimes nephrocalcinosis, and option C describes Liddle syndrome, which features suppressed rather than elevated renin and aldosterone.
Reference: Harrison's Principles of Internal Medicine, 21st ed.
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Written and medically reviewed by the StethoPrep medical team.