Liddle Syndrome (Pseudohyperaldosteronism)

Excerpt

Liddle syndrome is one of the rare causes of resistant hypertension that can present in early childhood, although some cases are not detected until adulthood. First described in 1963 by Grant Liddle et al, this syndrome is characterized by a primary increase in sodium reabsorption in the distal nephron leading to subsequent potassium secretion. For this reason, it is also known as pseudohyperaldosteronism.

The syndrome is a rare, monogenic, autosomal dominant cause of secondary hypertension resulting from a genetic gain-of-function mutation of the epithelial sodium channel (ENaC). Affected patients typically present with hypertension, hypokalemia, and metabolic alkalosis. Although these findings are similar to those seen in other disorders caused by mineralocorticoid excess, Liddle syndrome does not respond to aldosterone antagonism (eg, spironolactone). The mainstay of treatment is with ENaC blockers, including amiloride.