Liddle Syndrome: The Low-Aldosterone Clue

A 19-year-old patient presents with severe hypertension, muscle weakness, and recurrent hypokalemia. The laboratory findings reveal metabolic alkalosis, suppressed plasma renin, and surprisingly, low aldosterone. What is the diagnosis? **Liddle syndrome!** This is an autosomal dominant disorder caused by a gain-of-function mutation in the SCNN1B or SCNN1G gene. These genes encode the beta and gamma subunits of the epithelial sodium channel, or ENaC, located in the principal cells of the collecting duct. Normally, ENaC activity is regulated, partly through channel removal from the cell surface. In Liddle syndrome, defective channel removal causes ENaC to remain excessively active. Think: **ENaC is always ON!** Excess sodium reabsorption causes volume expansion and hypertension. The resulting electrical gradient promotes potassium and hydrogen ion secretion, producing hypokalemia and metabolic alkalosis. Volume expansion suppresses renin and aldosterone. Remember the classic examination combination: **Young patient. Severe hypertension. Low potassium. Metabolic alkalosis. Low renin. Low aldosterone.** Now the examiner's favorite trap! Primary hyperaldosteronism also causes hypertension and hypokalemia, but aldosterone is HIGH. In Liddle syndrome, aldosterone is LOW. What is the treatment? **Amiloride or triamterene!** These drugs directly block ENaC. Spironolactone is ineffective against the underlying defect because ENaC activation is independent of aldosterone. Final memory lock: **Liddle syndrome equals ENaC always ON, sodium retention, potassium loss, low renin, low aldosterone, and amiloride!**