A 22-year-old woman presents with recurrent muscle cramps and fatigue. Labs show K+ 2.9 mEq/L, HCO3 33 mEq/L, Mg 1.2 mg/dL, and urinary calcium excretion that is abnormally low. Blood pressure is normal. Genetic testing reveals loss-of-function mutations affecting a thiazide-sensitive transporter. Which segment of the nephron harbors the defective transporter?

• A Distal convoluted tubule ✓
• B Thick ascending limb of Henle's loop
• C Proximal convoluted tubule
• D Cortical collecting duct principal cells

Explanation

This is Gitelman syndrome, caused by loss-of-function mutations in the NCC (SLC12C3) sodium-chloride cotransporter of the distal convoluted tubule. Its signature features are hypokalemic metabolic alkalosis, hypomagnesemia, and hypocalciuria. Bartter syndrome, the key mimic, involves the thick ascending limb (NKCC2 or related channels) and produces hypercalciuria with normal or elevated urinary calcium, which excludes option B here.

Reference: Harrison's Principles of Internal Medicine, 21st ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.