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Disease Profile

Liddle syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.

Unknown

Age of onset

Adolescent

ICD-10

I15.1

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

Pseudoaldosteronism; Liddle's syndrome

Categories

Blood Diseases; Congenital and Genetic Diseases; Kidney and Urinary Diseases

Summary

Liddle syndrome is a rare, inherited condition that is primarily characterized by severe high blood pressure (hypertension) that often develops at an early age. Although the condition may not be associated with signs and symptoms initially, untreated hypertension can eventually lead to heart disease or stroke. Affected people may also have low levels of potassium in the blood (hypokalemia) and metabolic alkalosis. Liddle syndrome is caused by mutations in either the SCNN1B or SCNN1G genes and is inherited in an autosomal dominant manner. Treatment may include a low sodium diet and potassium-sparing diuretics to reduce blood pressure and normalize potassium levels. Conventional anti-hypertensive therapies are not effective.[1][2]

Symptoms

Liddle syndrome is primarily characterized by severe, early-onset hypertension (high blood pressure). Although the condition may not be associated with any signs and symptoms initially, untreated hypertension can eventually lead to heart disease and stroke. Affected people may also have hypokalemia (low blood potassium) and metabolic alkalosis. Symptoms of hypokalemia can include weakness, fatigue, muscle pain (myalgia), constipation or heart palpitations. In most cases, the condition becomes apparent at a young age but some affected people are not diagnosed until well into adulthood.[2][1]

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Arrhythmia
Abnormal heart rate
Heart rhythm disorders
Irregular heart beat
Irregular heartbeat

[ more ]

0011675
Constipation
0002019
Hypertension
0000822
Hypokalemia
Low blood potassium levels
0002900
30%-79% of people have these symptoms
Cerebral ischemia
Disruption of blood oxygen supply to brain
0002637
Fatigue
Tired
Tiredness

[ more ]

0012378
Muscle weakness
Muscular weakness
0001324
Nephropathy
0000112
Renal insufficiency
Renal failure
Renal failure in adulthood

[ more ]

0000083
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Decreased circulating aldosterone level
Low blood aldosterone level
0004319
Decreased circulating renin level
0003351
Hypokalemic alkalosis
0001949
Metabolic alkalosis
0200114

Cause

Liddle syndrome is caused by changes (mutations) in the SCNN1B or SCNN1G gene. Each of theses genes provides instructions for making one piece of a protein complex called the epithelial sodium channel (ENaC). These channels are found on the surface of certain cells (epithelial cells) throughout the body, including the kidneys, lungs, and sweat glands. The ENaC channel transports sodium into cells.[3][4]

Mutations in the SCNN1B and SCNN1G genes affect an important region of the protein involved in signaling for its breakdown (degradation). As a result of the mutations, the protein is not tagged for degradation when it is no longer needed, and more ENaC channels remain at the cell's surface. The increase in channels at the cell surface abnormally increases the reabsorption of sodium, which leads to hypertension. Because removal of potassium from the blood is linked with reabsorption of sodium, excess sodium reabsorption leads to hypokalemia.[1]

Diagnosis

A diagnosis of Liddle syndrome is often suspected based the presence of early-onset hypertension (high blood pressure), especially in people with a family history of the condition. Additional testing can then be ordered to confirm the diagnosis. This may include:[5][2]

  • Blood tests which can detect low levels of potassium, renin and aldosterone.
  • Urine tests to identify low levels of sodium and aldosterone.
  • Genetic testing to look for a change (mutation) in the SCNN1B or SCNN1G gene.

Testing Resources

  • The Genetic Testing Registry (GTR) provides information about the genetic tests for this condition. The intended audience for the GTR is health care providers and researchers. Patients and consumers with specific questions about a genetic test should contact a health care provider or a genetics professional.

    Treatment

    Treatment for Liddle syndrome consists of following a low sodium diet and taking potassium-sparing diuretics, which reduce blood pressure and correct hypokalemia and metabolic alkalosis. Conventional anti-hypertensive therapies are not effective for this condition.[5][2]

    Management Guidelines

    • Project OrphanAnesthesia is a project whose aim is to create peer-reviewed, readily accessible guidelines for patients with rare diseases and for the anesthesiologists caring for them. The project is a collaborative effort of the German Society of Anesthesiology and Intensive Care, Orphanet, the European Society of Pediatric Anesthesia, anesthetists and rare disease experts with the aim to contribute to patient safety.

      Organizations

      Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

      Organizations Providing General Support

        Learn more

        These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

        Where to Start

          In-Depth Information

          • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
          • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
          • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
          • PubMed is a searchable database of medical literature and lists journal articles that discuss Liddle syndrome. Click on the link to view a sample search on this topic.

            References

            1. Liddle syndrome. Genetics Home Reference. March 2013; https://ghr.nlm.nih.gov/condition/liddle-syndrome#.
            2. William F. Young, Jr. Genetic disorders of the collecting tubule sodium channel: Liddle's syndrome and pseudohypoaldosteronism type 1. UpToDate. Waltham, MA: UpToDate; 2016;
            3. SCNN1B. Genetics Home Reference. March 2013; https://ghr.nlm.nih.gov/gene/SCNN1B.
            4. SCNN1G. Genetics Home Reference. March 2013; https://ghr.nlm.nih.gov/gene/SCNN1G.
            5. Rosa Vargas-Poussou. Liddle syndrome. Orphanet. August 2011; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=EN&Expert=526.

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