Skip to
  1. Homepage
  2. Rare diseases
  3. Search
Simple search

Simple search

*
(*) mandatory field





 

Other search option(s)

Liddle syndrome

Orpha number ORPHA526
Synonym(s) Pseudoaldosteronism
Pseudohyperaldosteronism type 1
Prevalence <1 / 1 000 000
Inheritance
  • Autosomal dominant
Age of onset Childhood
ICD-10
  • I15.1
OMIM
UMLS
  • C0221043
MeSH
  • D056929
MedDRA
  • 10037113
  • 10052313
SNOMED CT
  • 71275003

Summary

Liddle syndrome is a rare inherited form of hypertension characterized by severe early-onset hypertension associated with decreased plasmatic levels of potassium, renin and aldosterone.

Prevalence is unknown. About 80 cases have been reported to date.

Severe hypertension is found in young patients, from infancy to young adulthood (<35 years of age). Children are usually asymptomatic. Adults can present with symptoms of hypokalemia such as weakness, fatigue, myalgia, constipation or palpitations. A family history of hypertension across several generations suggesting autosomal dominant inheritance is often present.

Liddle syndrome is due to gain-of-function mutations in the genes encoding the epithelial sodium channel (ENaC), involved in sodium reabsorption of the distal renal tubules. The channel comprises three subunits (alpha, beta, gamma) and the mutations occur on the C-terminus of the beta and gamma subunits, encoded by the SCNN1B and SCNN1G genes (16p13-p12) respectively, in proline-rich region called the PY motif. These mutations impair ENaC interaction with the Nedd4 (E3 ligase) protein and its subsequent degradation by the ubiquitin proteasome system. This results in constitutive expression of ENaC channels in the membrane inducing sodium reabsorption, secondary potassium secretion and ultimately, hypertension.

Diagnosis is suspected by the fortuitous detection of early-onset hypertension, especially in the presence of family history. It is then confirmed by blood and urinary electrolyte tests which show hypokalemia, decreased or normal plasma levels of renin and aldosterone, metabolic alkalosis with high sodium plasma levels, and low rates of urinary excretion of sodium and aldosterone with high rates of urinary potassium excretion. The diagnosis is confirmed by genetic testing.

The clinical picture resembles that of primary hyperaldosteronism (see this term) but the hormonal profile resembles that of hyporeninism-hypoaldosteronism (see this term).

Transmission is autosomal dominant.

Treatment is based on administration of potassium-sparing diuretics, such as amiloride or triamterene, which act by blocking ENaC activity. This results in reduction of blood pressure and correction of hypokalemia and metabolic alkalosis. Conventional antihypertensive therapies are not effective. Patients must also follow a low sodium diet.

With treatment, prognosis is good. Without treatment, cardiovascular and renal complications usually occur.

Expert reviewer(s)

  • Dr Rosa VARGAS-POUSSOU

(*) Required fields.

Attention: Only comments seeking to improve the quality and accuracy of information on the Orphanet website are accepted. For all other comments, please send your remarks via contact us. Only comments written in English can be processed.


Captcha image

Detailed information

Summary information
Get Acrobat Reader
The documents contained in this web site are presented for information purposes only. The material is in no way intended to replace professional medical care by a qualified specialist and should not be used as a basis for diagnosis or treatment.