Liddle syndrome

Liddle syndrome, also known as Liddle's syndrome or pseudoaldosteronism, is a rare hereditary form of hypertension caused by gain-of-function mutations in the genes encoding the epithelial sodium channel (ENaC) subunits. Specifically, mutations in the SCNN1B gene (encoding the beta subunit) or the SCNN1G gene (encoding the gamma subunit) on chromosome 16p12 lead to constitutive activation of ENaC in the distal nephron of the kidney. This results in excessive sodium reabsorption and potassium excretion, mimicking a state of mineralocorticoid excess but with characteristically low levels of aldosterone and renin. The condition primarily affects the cardiovascular and renal systems. Patients typically present with early-onset, often severe hypertension that may begin in childhood or adolescence. Key clinical features include hypokalemia (low potassium levels), metabolic alkalosis, and suppressed plasma renin activity and aldosterone levels. If left untreated, the persistent hypertension can lead to serious complications including stroke, heart failure, kidney damage, and retinopathy. Some patients may be relatively asymptomatic and discovered incidentally through blood pressure screening or electrolyte abnormalities. Treatment of Liddle syndrome is distinct from typical hypertension management. Standard antihypertensive medications and mineralocorticoid receptor antagonists such as spironolactone are ineffective because the defect is downstream of the aldosterone receptor. Instead, the condition responds specifically to ENaC blockers, particularly amiloride and triamterene, which directly inhibit the overactive sodium channel. Dietary sodium restriction is also recommended as an adjunctive measure. With appropriate treatment, blood pressure and electrolyte abnormalities can be well controlled, and patients can have a good long-term prognosis. Genetic testing confirms the diagnosis and enables screening of at-risk family members.

Common questions about Liddle syndrome