Liddle’s syndromeis a genetic disorder inherited in an autosomal dominant manner that is characterized by early, and frequently severe, high blood pressure associated with low plasma renin activity, metabolic alkalosis, low blood potassium, and normal to low levels of aldosterone.
Liddle syndrome involves abnormal kidney function, with excess reabsorption of sodium and loss of potassium from the renal tubule.
It is treated with a combination of low sodium diet and potassium-sparing diuretics.
It is extremely rare, with fewer than 30 pedigrees or isolated cases having been reported worldwide.
Liddle syndrome is caused by dysregulation of the epithelial sodium channel (ENaC) due to a genetic mutation at the 16p13-p12 locus.
Such epithelial sodium channels are found on the surface of epithelial cells found in the kidneys, lungs, and sweat glands, and transport sodium into cells.
The mutation prevents ubiquitin proteasome system correct degradation.
leads to a hyperaldosteronism-like state, since aldosterone is typically responsible for creating and inserting these channels.
It leads to increased sodium resorption, increased resorption of water, and hypertension due to an increase in extracellular volume.
The serum sodium is typically elevated, the serum potassium is reduced,
and the serum bicarbonate is elevated.
While primary hyperaldosteronism is due to an aldosterone-secreting adrenal tumor or adrenal hyperplasia.
Aldosterone levels are high in hyperaldosteronism, whereas they are low to normal in Liddle syndrome.
A genetic study of the epithelial sodium channel (ENaC) sequences can detect mutations (deletions, insertions, missense mutations) for diagnosis.
The treatment is with a low sodium diet and a potassium-sparing diuretic that directly blocks the sodium channel.
Potassium-sparing diuretics that are effective.
Spironolactone is not effective because it acts by regulating aldosterone and Liddle syndrome does not respond to this regulation.
Amiloride is safe in pregnancy.
Treatment usually corrects both the hypertension and hypokalemia.
Liddle syndrome resolves completely after kidney transplantation.