Liddle syndrome I15.80

Rare, autosomal dominant inherited form of arterial hypertension characterized by severe, early onset hypertension with decreased potassium, renin and aldosterone plasma levels.

Prevalence: <1 / 1 000 000

mutations in genes coding for the epithelial sodium (Na) channel (ENaC). This channel is responsible for the reabsorption of sodium into the distal tubules of the kidney. The channel has three subunits (alpha, beta, gamma), and the mutations are located at the C-terminus of the beta and gamma subunits in a proline-rich region called the PY motif. The two subunits are encoded by the genes SCNN1B and SCNN1G (16p13-p12) respectively. These mutations impair the interaction of ENaC with the Nedd4 protein (E3 ligase) and the subsequent degradation in the system of the ubiquitin proteasome. As a result, the epithelial Na channels are constitutively active and the permanent reabsorption of Na leads secondarily to potassium secretion and thus to hypertension.

Infancy

Hypertension is discovered in young patients, from infancy to early adulthood (< 35 years). Adults show symptoms of hypokalemia, such as weakness, fatigue, myalgia, constipation or palpitations. Families often report about affected persons from several generations.

Potassium-sparing diuretics (e.g. amiloride and triamterene), which act by blocking ENaC activity This leads to a reduction in blood pressure; further corrects hypokalemia and metabolic alkalosis. In addition, patients must follow a low-sodium diet. Conventional antihypertensive drugs are ineffective.

With treatment favorable prognosis. Untreated patients usually suffer cardiovascular and renal complications.

1. Tetti M et al. (2018) Liddle syndrome: Review of the Literature andDescription of a New Case. Int J Mol Sci 19:812.
2. Enslow BT et al (2019) Liddle's syndrome mechanisms, diagnosis and management. Integr Blood Press Control 12:13-22.