Genetic disorders of the collecting tubule sodium channel: Liddle's syndrome and pseudohypoaldosteronism type 1
- William F Young, Jr, MD, MSc
William F Young, Jr, MD, MSc
- Professor of Medicine
- Mayo Clinic College of Medicine
- Section Editors
- Richard H Sterns, MD
Richard H Sterns, MD
- Editor-in-Chief — Nephrology
- Section Editor — Fluid and Electrolytes
- Professor Emeritus
- University of Rochester School of Medicine and Dentistry
- André Lacroix, MD
André Lacroix, MD
- Section Editor — Adrenal Disease
- Professor of Medicine
- University of Montreal, Quebec, Canada
Liddle's syndrome and autosomal recessive pseudohypoaldosteronism type 1 are rare genetic disorders associated with abnormalities in the function of the collecting tubule sodium channel, also called the epithelial sodium channel (ENaC) or the amiloride-sensitive sodium channel:
●ENaC function is increased in Liddle's syndrome, leading to manifestations similar to those caused by mineralocorticoid excess, such as hypertension and, in some patients, hypokalemia and metabolic alkalosis. Presentation at a young age, which occurs in most patients, suggests the possibility of a genetic disorder rather than an adrenal adenoma. In addition, plasma and urinary aldosterone levels are reduced, not increased as in primary aldosteronism.
●ENaC function is decreased in autosomal recessive pseudohypoaldosteronism type 1, resulting in aldosterone resistance. Affected patients present in infancy with sodium wasting, hypovolemia, and hyperkalemia. These findings are similar to those in other forms of hypoaldosteronism in children, except that plasma aldosterone levels are elevated, not reduced.
The clinical presentation, genetics, and management of Liddle's syndrome and pseudohypoaldosteronism will be reviewed here. Other causes of hypertension and hypokalemia, and of hypoaldosteronism are reviewed separately. (See "Diagnosis of primary aldosteronism" and "Etiology, diagnosis, and treatment of hypoaldosteronism (type 4 RTA)".)
COLLECTING TUBULE SODIUM CHANNEL
The cortical collecting tubule contains two cell types with different functions: principal cells (about 65 percent) and intercalated cells:
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