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Liddle’s syndrome mechanisms, diagnosis and management

Authors Enslow BT, Stockand JD, Berman JM

Received 25 May 2019

Accepted for publication 23 August 2019

Published 3 September 2019 Volume 2019:12 Pages 13—22


Checked for plagiarism Yes

Review by Single-blind

Peer reviewer comments 3

Editor who approved publication: Dr Konstantinos Tziomalos

Video abstract presented by Jonathan M Berman.

Views: 567

Benjamin T Enslow1, James D Stockand1, Jonathan M Berman2

1UT Health, San Antonio, TX, USA; 2New York Institute of Technology College of Osteopathic Medicine at Arkansas State University, Jonesboro, AR, USA

Corrspondence: Jonathan M Berman
New York Institute of Technology at Arkansas State University, Jonesboro, AR 72467, USA
Tel +1 870 680 8896

Abstract: Liddle’s syndrome is a genetic disorder characterized by hypertension with hypokalemic metabolic alkalosis, hyporeninemia and suppressed aldosterone secretion that often appears early in life. It results from inappropriately elevated sodium reabsorption in the distal nephron. Liddle’s syndrome is 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 and animal models. Liddle’s syndrome can be diagnosed clinically by phenotype and confirmed through genetic testing. This review examines the clinical features of Liddle’s syndrome, the differential diagnosis of Liddle’s syndrome and differentiation from other genetic diseases with similar phenotype, and what is currently known about the population-level prevalence of Liddle’s syndrome. This review gives special focus to the molecular mechanisms of Liddle’s syndrome.

Keywords: ENaC, Liddle’s syndrome, hypertension, blood pressure, distal nephron

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