Liddle's syndrome

Liddle's syndrome was originally described by the late Grant Liddle in 1963 as a disease which mimicked, quite remarkably, primary aldosteronism. That is, the features of the disease included volume expansion, hypertension, and hypokalemic metabolic alkalosis. We now know, beginning with molecular studies on the original patient described by Liddle, that the disease represents a specific defect in apical membranes of principal cells. In this paper, Palmer and Alpern provide a clear explanation of the constitutive activation of apical Na⁺ channels in principal cells of collecting ducts. In short, in some 35 years, we have gone from a brilliant set of clinical deductions by Grant Liddle to a meticulous molecular description of the defect in Liddle's syndrome. To be sure, Liddle's syndrome, by itself, is a rarity. Yet formes frustes of Liddle's syndrome may well underlie many of the sodium-sensitive forms of hypertension seen in our country.