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Liddle syndrome
Clinical feature:
Definition: The Liddle syndrome is an autosomal dominant form of hereditary hypertension and hypokalemia.
Pathogenesis: The reason for this disease is a permanent activation of renal epithelial sodium channel (ENaC). Mutations in beta and gamma subunit of this channel prevent the closure of this channel in case of height intracellular sodium concentrations.
Clinical picture: In this inherited disease the symptoms resemble aldosteronism (hypokalemia, volume expension, hypertension, metabolic alkalosis) despite a suppressed renin and aldosterone secretion.
Aldosteron-sensitivity persists so aldosteron administration can make the symptoms worse.
Spironolacton, the aldosterone antagonist, has little effect. This is not surprising, for the aldosterone levels low already. In contrary, the positive effect of amiloride and triamterene, the selective blockers of the aldosteron sensitive sodium channel, is of pathognomonic evidence. Diet should be low in sodium and rich in potassium.
Diagnostics:
Diagnosis: The diagnosis is made by the typical combination of hypertension, hypokalemia, metabolic alkalosis, hyporeninemia and hypoaldosteronemia. Because of the dominant inheritance there is often a positive family history. To test the effectiveness of amiloride and triamterene is essential.
Differential: Apparent mineralocoirticoid excess (AME) presents with similar clinical symptoms (hypokalemia, hypertension, supressed renin and aldosterone) but effectively responds to spironolactone and dexamethasone treatment.
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The regulation of the aldosterone sensitive sodium channel is a complex process with many genes involved, so it is not surprising that still not all of them are discovered.
Strategy: For exclusion of secondary hypertension, volume expansion and potassium concentration is regularly measured. Additionally, aldosterone secretion can be measured in daily urine. If all these data indicated Liddle syndrome a molecular diagnostic can be used to confirm.
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