Liddle syndrome

Other Names: Pseudoaldosteronism; Liddle's syndrome Liddle syndrome is an inherited form of high blood pressure (hypertension). This condition is characterized by severe hypertension that begins unusually early in life, often in childhood, although some affected individuals are not diagnosed until adulthood. Some people with Liddle syndrome have no additional signs or symptoms, especially in childhood. Over time, however, untreated hypertension can lead to heart disease or stroke, which may be fatal.

Epidemiology

Liddle syndrome is a rare condition, although its prevalence is unknown. The condition has been found in populations worldwide.

Cause

Liddle syndrome is caused by mutations in the SCNN1B or SCNN1G gene. Each of these genes provides instructions for making a piece (subunit) of a protein complex called the epithelial sodium channel (ENaC). These channels are found at the surface of certain cells called epithelial cells in many tissues of the body, including the kidneys, where the channels transport sodium into cells.

In the kidney, ENaC channels open in response to signals that sodium levels in the blood are too low, which allows sodium to flow into cells. From the kidney cells, this sodium is returned to the bloodstream (a process called reabsorption) rather than being removed from the body in urine.

Mutations in the SCNN1B or SCNN1G gene change the structure of the respective ENaC subunit. The changes alter a region of the subunit that is involved in signaling for its breakdown (degradation) when it is no longer needed. As a result of the mutations, the subunit proteins are not degraded, and more ENaC channels remain at the cell surface. The increase in channels at the cell surface abnormally increases the reabsorption of sodium (followed by water), which leads to hypertension. Reabsorption of sodium into the blood is linked with removal of potassium from the blood, so excess sodium reabsorption leads to hypokalemia.

Inheritance

Autosomal dominant pattern, a 50/50 chance.

This condition is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder.

Signs and symptoms

Liddle syndrome is primarily characterized by severe, early-onset hypertension (high blood pressure). Although the condition may not be associated with any signs and symptoms initially, untreated hypertension can eventually lead to heart disease and stroke. Affected people may also have hypokalemia (low blood potassium) and metabolic alkalosis. Symptoms of hypokalemia can include weakness, fatigue, muscle pain (myalgia), constipation or heart palpitations. In most cases, the condition becomes apparent at a young age but some affected people are not diagnosed until well into adulthood. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed.

80%-99% of people have these symptoms

• Arrhythmia(Abnormal heart rate)
• Constipation
• Hypertension
• Hypokalemia(Low blood potassium levels)

30%-79% of people have these symptoms

• Cerebral ischemia(Disruption of blood oxygen supply to brain)
• Fatigue(Tired)
• Muscle weakness(Muscular weakness)
• Nephropathy
• Renal insufficiency(Renal failure)

Diagnosis

A diagnosis of Liddle syndrome is often suspected based the presence of early-onset hypertension (high blood pressure), especially in people with a family history of the condition. Additional testing can then be ordered to confirm the diagnosis. This may include:

• Blood tests which can detect low levels of potassium, renin and aldosterone.
• Urine tests to identify low levels of sodium and aldosterone.
• Genetic testing to look for a change (mutation) in the SCNN1B or SCNN1G gene.

Treatment

Treatment for Liddle syndrome consists of following a low sodium diet and taking potassium-sparing diuretics, which reduce blood pressure and correct hypokalemia and metabolic alkalosis. Conventional anti-hypertensive therapies are not effective for this condition. 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. Amiloride is the only treatment option that is safe in pregnancy.

Medical treatment usually corrects both the hypertension and the hypokalemia, and as a result these patients may not require any potassium replacement therapy.

Liddle syndrome resolves completely after kidney transplantation.

Prognosis

With treatment, the long-term outlook (prognosis) for people with Liddle syndrome is good. However, untreated hypertension may lead to stroke, heart disease and/or kidney problems which can be fatal.

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NIH genetic and rare disease info

• NIH info on Liddle syndrome

Liddle syndrome is a rare disease.

Liddle syndrome Resources
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