Liddle Syndrome – Clinician Information

  • Background

    Liddle Syndrome is a rare genetic disorder that causes persistent hypertension accompanied by hypokalaemia from a young age, typically early teenage onwards. Children with high blood pressure may show poor growth and blood pressure should be checked in any child or adolescent who is not growing well. Note that the hypertension may not be equally severe in all those with Liddle’s in a given family. This is because there are many other genetic and lifestyle events that can modify blood pressure in an individual.

    Unrecognised or uncontrolled high blood pressure can lead to stroke, heart failure, eyesight problems and kidney damage (including end-stage kidney disease). All of these can be prevented by early recognition and good blood pressure control.

    The cause is a mutation in either the beta- or gamma-subunit of the epithelial sodium channel (ENaC) in the distal nephron. Paradoxically, this leads to overactivity of the channel, and therefore salt retention with hypokalaemia, hypertension and (appropriate) suppression of renin/aldosterone.

  • Clinical Diagnosis

    Suspect when:

    • There is high blood pressure (adjusted for age) in anyone below 40 years of age, and especially in children.
    • There is a family history of hypertension. Liddle Syndrome is an autosomal dominant single-gene disorder. If one person in a family has been diagnosed, it is important that other relatives get their blood pressure measured. This advice also applies to children.
    • There is unexplained poor growth.

     

    Biochemical diagnosis:

    • Hypokalaemia
    • Elevated/high normal venous bicarbonate
    • Suppressed renin and aldosterone
  • Treatment

    Amiloride (or triamterene), a blocker of the epithelial sodium channel, is the drug of choice. If other anti-hypertensives are already in use, they may be able to be stopped.

    Treatment must be combined with a low salt diet. (See Dietary Needs)

  • Monitoring

    Liddle Syndrome is a life-long condition requiring continued treatment and regular medical appointments and occasional blood tests. If untreated, CKD may supervene.

  • Genetic Diagnosis

    A DNA test may be useful as it can be used to diagnose or rule out Liddle Syndrome in at-risk family members if a mutation is found. Appropriate genetic counselling should be undertaken prior to testing. Testing is available through the East Anglian Regional Molecular Genetics laboratories.

Liddle Syndrome Clinician Information Version 5 Updated April 2017
Written by the Hypokalaemic Alkaloses Rare Disease Group