Liddle syndrome

What it is

Liddle syndrome is autosomal dominant, caused by a gain-of-function genetic mutation in ENaC, the epithelial sodium channel of the collecting duct. The overactive ENaC increases sodium reabsorption, and that reabsorption is independent of aldosterone. Volume expansion follows, and with it hypertension.

How it presents

Early-onset hypertension with hypokalemia is the picture. Blood pressure is high because of the increased sodium reabsorption. Metabolic alkalosis is present. Calcium handling is normal and magnesium is normal, which is part of what separates it from the other tubular syndromes.

How it is diagnosed

The findings are:

• Hypokalaemia
• Metabolic alkalosis
• Decreased renin and aldosterone levels, both suppressed, the aldosterone because of volume expansion

In a patient with hypokalemia and hypertension, suspected mineralocorticoid excess sorts into three groups by renin and aldosterone:

• Primary: renin low or normal, aldosterone high
• Secondary: renin high, aldosterone high
• Mimickers: renin low or normal, aldosterone low or normal

Liddle syndrome is one of the mimickers, alongside Cushing's disease and exogenous ingestion. Adrenal adenoma and congenital hyperplasia are the primary group, and renal tumor, cortication of aorta and renal A. stenosis are the secondary group.

Metabolic alkalosis is an arterial pH above 7.45 with a serum HCO3 above 24 mEq/L, and the first thing to look at is the chloride level:

• Low urine chloride: vomiting or nasogastric aspiration, and prior diuretic use. Saline-responsive.
• High urine chloride with hypovolemia or euvolemia: current diuretic use, which sits on the saline-responsive side, and Bartter and Gitelman syndromes, which are saline-unresponsive.
• High urine chloride with hypervolemia: excess mineralocorticoid activity, covering primary hyperaldosteronism, Cushing disease and ectopic ACTH production. Saline-unresponsive.

Bartter and Gitelman syndromes are marked as the group without hypertension and excess mineralocorticoid activity as the group with hypertension, and Liddle syndrome belongs with the hypertensive causes here as well.