Grant Liddle (1921–1989), an American endocrinologist at Vanderbilt University, who described it in 1963. Liddle syndrome resolves completely after kidney transplantation. Medical treatment usually corrects both the hypertension and the hypokalemia, and as a result these patients may not require any potassium replacement therapy. Amiloride is the only treatment option that is safe in pregnancy. Potassium-sparing diuretics that are effective for this purpose include amiloride and triamterene spironolactone is not effective because it acts by regulating aldosterone and Liddle syndrome does not respond to this regulation. The treatment is with a low sodium (low salt) diet and a potassium-sparing diuretic that directly blocks the sodium channel.
Ī genetic study of the ENaC sequences can be requested to detect mutations (deletions, insertions, missense mutations) and get a diagnosis. Aldosterone levels are high in hyperaldosteronism, whereas they are low to normal in Liddle syndrome. Primary hyperaldosteronism (also known as Conn's syndrome), is due to an aldosterone-secreting adrenal tumor ( adenoma) or adrenal hyperplasia. These findings are also found in hyperaldosteronism, another rare cause of hypertension in children. In Liddle's disease, the serum sodium is typically elevated, the serum potassium is reduced, and the serum bicarbonate is elevated. Diagnosis Įvaluation of a child with persistent high blood pressure usually involves analysis of blood electrolytes and an aldosterone level, as well as other tests. Liddle syndrome is inherited in an autosomal dominant fashion. The increased sodium resorption leads to increased resorption of water, and hypertension due to an increase in extracellular volume. This results in a hyperaldosteronism-like state, since aldosterone is typically responsible for creating and inserting these channels. This loss of ability to be degraded leads to high amounts of the channel being chronically present in the collecting duct. Specifically, the PY motif in the protein is deleted or altered so the E3 ligase (Nedd4) no longer recognizes the channel.
The mutation changes a domain in the channel so it is no longer degraded correctly by the ubiquitin proteasome system. These channels are found on the surface of epithelial cells found in the kidneys, lungs, and sweat glands. This syndrome is caused by dysregulation of the epithelial sodium channel ( ENaC) due to a genetic mutation at the 16p13-p12 locus. Additionally, long-standing hypertension could become symptomatic.
Īdults could present with nonspecific symptoms of low blood potassium, which can include weakness, fatigue, palpitations or muscular weakness ( shortness of breath, constipation/abdominal distention or exercise intolerance). Because this syndrome is rare, it may only be considered by the treating physician after the child's hypertension does not respond to medications for lowering blood pressure. The first indication of the syndrome often is the incidental finding of hypertension during a routine physical exam. Children with Liddle syndrome are frequently asymptomatic.