Liddle's syndrome

Last edited 07/2021 and last reviewed 03/2022

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