What is Liddle syndrome (Pseudohyperaldosteronism)?

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From the Guidelines

Liddle Syndrome

Liddle syndrome is a rare genetic disorder characterized by excessive sodium absorption and water retention, leading to hypertension and hypokalemia 1.

Key Features

The key features of Liddle syndrome include:

  • Suppressed plasma renin activity (PRA)
  • Increased sodium absorption in the distal tubule
  • Serum potassium abnormalities
  • Metabolic acid-base disturbances
  • Abnormal plasma aldosterone concentrations 1

Treatment

The primary treatment for Liddle syndrome involves the use of potassium-sparing diuretics, such as triamterene (50-100 mg daily) or amiloride (5-10 mg daily), to help reduce sodium absorption and increase potassium levels 1. Additionally, patients may be advised to follow a low-sodium diet and restrict their sodium intake to less than 2 grams per day.

Management

In some cases, other medications such as spironolactone (25-50 mg daily) may be used off-label to help manage the condition 1. It is essential to monitor blood pressure, electrolyte levels, and kidney function regularly while on treatment. Lifestyle modifications, including regular exercise, weight management, and stress reduction, can also help manage the condition 1. Patients with Liddle syndrome should work closely with their healthcare provider to develop a personalized treatment plan and make adjustments as needed to achieve optimal blood pressure control and prevent long-term complications.

From the Research

Definition and Characteristics of Liddle Syndrome

  • Liddle syndrome, also known as pseudohyperaldosteronism, is a rare autosomal dominant disease that mimics primary hyperaldosteronism 2, 3, 4, 5, 6.
  • It is characterized by early-onset hypertension, hypokalemia, and hypoaldosteronism, caused by excessive salt and water reabsorption in the distal nephron 2, 3.
  • The syndrome is often associated with hyporeninemia and suppressed aldosterone secretion, which can lead to metabolic alkalosis 3, 4, 5, 6.

Causes and Molecular Mechanisms

  • Liddle syndrome is caused by mutations in the genes encoding the subunits of the Epithelial Sodium Channel (ENaC), specifically SCNN1A, SCNN1B, and SCNN1G 3, 4, 6.
  • These mutations can lead to an increase in ENaC activity, resulting in excessive sodium reabsorption and subsequent hypertension and hypokalemia 3, 4, 6.

Diagnosis and Treatment

  • Liddle syndrome can be diagnosed clinically by phenotype and confirmed through genetic testing 3, 5, 6.
  • Treatment typically involves the use of potassium-sparing diuretics, such as amiloride and triamterene, which can reduce ENaC activity and restore normotension and electrolyte balance 3, 4, 6.
  • A reduced sodium diet is also often recommended as part of the treatment plan 3.

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Liddle's syndrome: A case report.

Saudi journal of kidney diseases and transplantation : an official publication of the Saudi Center for Organ Transplantation, Saudi Arabia, 2015

Research

Liddle's syndrome mechanisms, diagnosis and management.

Integrated blood pressure control, 2019

Research

[Liddle syndrome as a rare cause of hypertension - a case report].

Polski merkuriusz lekarski : organ Polskiego Towarzystwa Lekarskiego, 2019

Research

Liddle Syndrome: Review of the Literature and Description of a New Case.

International journal of molecular sciences, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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