What is the genetic defect in liddle syndrome, and how are such patients treated?
Liddle syndrome is a rare (∼30 pedigrees described through 2008) autosomal-dominant disorder caused by a gain of function mutation of the epithelial sodium channel (ENaC) in the cortical collecting tubule. The mutation causes increased sodium reabsorption, volume expansion, and blood pressure. The clinical presentation is distinguished from hyperaldosteronism by the low serum aldosterone, but hypokalemia, metabolic alkalosis, and hypertension are present in both. Treatment with amiloride or triamterene blocks the constituently active ENaC in the collecting tubule, corrects the hypokalemia, and lowers blood pressure. Spironolactone or eplerenone is ineffective because aldosterone is not primarily involved in the pathogenesis of Liddle syndrome.
