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Liddle's syndrome

Last reviewed dd mmm yyyy. Last edited dd mmm yyyy

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Liddle's syndrome is a rare inherited disorder characterised by hypokalaemic alkalosis, hypertension, and negligible aldosterone secretion.

  • results from inappropriately elevated sodium reabsorption in the distal nephron
    • caused by mutations to subunits of the Epithelial Sodium Channel (ENaC)
      • among other mechanisms, such mutations typically prevent ubiquitination of these subunits, slowing the rate at which they are internalized from the membrane, resulting in an elevation of channel activity
      • a minority of Liddle's syndrome mutations, though, result in a complementary effect that also elevates activity by increasing the probability that ENaC channels within the membrane are open
  • potassium-sparing diuretics such as amiloride and triamterene reduce ENaC activity, and in combination with a reduced sodium diet can restore normotension and electrolyte imbalance in Liddle’s syndrome patients

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