Liddle syndrome

Liddle syndrome is an autosomal dominant disorder due to mutation of epithelial Na+ channels (i.e. ENaC); causes increased absorption of sodium in collecting tubules (due to increased activity of ENaC).

Pathogenesis:- Normally, ENaC are degraded by ubiquitin proteasome pathway; Nedd4-2 (i.e. ubiquitin-protein ligase) binds with ENaC and facilitates its degradation. ENaC is activated by aldosterone via the RAAS pathway (i.e. Aldosterone activates serum and glucocorticoid-regulated kinase (SGK)-1; SGK-1 phosphorylates and inactivates Nedd4-2 that cannot bind with ENaC preventing its degradation). However, in Liddle syndrome mutated epithelial Na+ channels cannot bind with Nedd4-2 preventing its degradation and causing its increased activation.

Presents with hypertension, hypokalemia, metabolic alkalosis; Laboratory parameters show low plasma aldosterone and low renin activity.

Management:-

1. Salt restriction.

2. ENaC blockers (e.g. Amiloride); Amiloride also is useful for lithium-induced nephrogenic diabetes insipidus as it blocks Li+ transport into collecting tubule cells.