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Disease Profile

Hypokalemic periodic paralysis

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.
1-9 / 100 000

3,310 - 29,790

US Estimated

1-9 / 100 000

5,135 - 46,215

Europe Estimated

Age of onset

Childhood

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ICD-10

G72.3

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)

HOKPP; HypoPP

Categories

Congenital and Genetic Diseases; Nervous System Diseases

Summary

Hypokalemic periodic paralysis (HOKPP) is characterized by episodes of muscle paralysis associated with a fall in blood potassium levels (hypokalemia).[1] Episodes typically involve a temporary inability to move muscles in the arms and legs.[2] The first attack usually occurs in childhood or adolescence. Attacks can last for hours or days, and the frequency of attacks varies among people with HOKPP. The frequency is usually highest between the ages of 15 and 35, and then decreases with age. Some people with HOKPP also develop late-onset proximal myopathy.[3]

HOKPP can be caused by mutations in the CACNA1S, SCN4A, or KCNJ18 gene. Inheritance is autosomal dominant. Treatment varies depending on the intensity and duration of attacks. Minor attacks may go away on their own, while treatment for moderate or severe attacks may involve taking potassium salts or intravenous (IV) potassium.[3]

Symptoms

HOKPP is characterized by attacks of muscle weakness or loss of muscle movement (paralysis) that come and go. The weakness or paralysis is most commonly located in the shoulders and hips, affecting the muscles of the arms and legs. Muscles of the eyes and those that help you breathe and swallow may also be affected.[4] While muscle strength is usually regained between attacks, repeated episodes can lead to persistent muscle weakness later in life.[2][4]

Attacks usually begin in childhood or adolescence, and the frequency of attacks varies. Some people have attacks every day, while others have them once a year. Attacks usually last at least a few hours, to sometimes days.[4][3] Attacks can occur without warning or they may be triggered by factors such as carbohydrate-rich meals and rest after exercise.[3]

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
100% of people have these symptoms
Episodic hypokalemia
Recurrent low potassium
0012726
Periodic hypokalemic paresis
0008153
80%-99% of people have these symptoms
EMG abnormality
0003457
Episodic flaccid weakness
0003752
Increased intramyocellular lipid droplets
0012240
Mildly elevated creatine kinase
0008180
30%-79% of people have these symptoms
Exercise-induced muscle fatigue
0009020
Postprandial hyperglycemia
0011998
5%-29% of people have these symptoms
Late-onset proximal muscle weakness
0003694
Myopathy
Muscle tissue disease
0003198
1%-4% of people have these symptoms
Adrenocortical adenoma
0008256
Fatigable weakness of respiratory muscles
0030196
Respiratory paralysis
0002203
Percent of people who have these symptoms is not available through HPO
Autosomal dominant inheritance
0000006
Hypokalemia
Low blood potassium levels
0002900
Incomplete penetrance
0003829

Cause

HOKPP can be caused by mutations in any of at least 3 known genes: CACNA1S, SCN4A, or KCNJ18. All three of these genes give the body instructions to make parts of ion channels that are primarily expressed in skeletal muscle cells.[3] Muscle contractions are triggered by the flow of ions into muscle cells. Mutations that cause HOKPP affect the usual structure or function of ion channels, impairing their ability to regulate the flow of ions into muscle cells. This, in turn, reduces the ability of skeletal muscles to contract, causing the weakness and paralysis associated with HOKPP.[2]

Not all people with a clinical diagnosis of HOKPP are found to have a mutation in one of the genes mentioned above. This suggests that other, yet unidentified genes may also be responsible for the condition.[3]

Diagnosis

A clinical diagnosis of HOKPP is based on:[3]

  • a history of episodes of paralysis
  • low levels of potassium during attacks, but not between attacks
  • the identification of typical "triggers" (i.e., rest after exercise, prolonged immobility)
  • a family history consistent with autosomal dominant inheritance. The diagnosis cannot be established by clinical findings alone in the absence of a known family history of the condition.

Various types of tests including blood tests, urine tests, and/or electromyograms may be used to differentiate between primary HOKPP and other possible causes of symptoms.[3]

Of all individuals who meet diagnostic criteria and have genetic testing, approximately 60% have mutations in the CACNA1S gene, approximately 20% in the SCN4A gene, and approximately 3.5% in the KCNJ18 gene. No other genes have yet been found to cause HOKPP, suggesting that other, unidentified genes may be responsible for the condition.[3]

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

    The resources below provide information about treatment options for this condition. If you have questions about which treatment is right for you, talk to your healthcare professional.

    Management Guidelines

    • Orphanet Emergency Guidelines is an article which is expert-authored and peer-reviewed that is intended to guide health care professionals in emergency situations involving this condition.

      FDA-Approved Treatments

      The medication(s) listed below have been approved by the Food and Drug Administration (FDA) as orphan products for treatment of this condition. Learn more orphan products.

      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 Supporting this Disease

        Social Networking Websites

          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

            • MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
            • Genetics Home Reference (GHR) contains information on Hypokalemic periodic paralysis. This website is maintained by the National Library of Medicine.
            • The National Institute of Neurological Disorders and Stroke (NINDS) collects and disseminates research information related to neurological disorders. Click on the link to view information on this topic.

              In-Depth Information

              • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
              • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
              • 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 Hypokalemic periodic paralysis. Click on the link to view a sample search on this topic.

                References

                1. Bertrand Fontaine. Hypokalemic Periodic Paralysis. Orphanet. June, 2007; https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=681.
                2. Hypokalemic periodic paralysis. Genetics Home Reference. April 2007; https://ghr.nlm.nih.gov/condition=hypokalemicperiodicparalysis.
                3. Savine Vicart, et al. Hypokalemic Periodic Paralysis. GeneReviews. July 31, 2014; https://www.ncbi.nlm.nih.gov/books/NBK1338/.
                4. Hypokalemic periodic paralysis. MedlinePlus. October 13, 2015; https://www.nlm.nih.gov/medlineplus/ency/article/000312.htm.
                5. Laurie Gutmann. Hypokalemic periodic paralysis. UpToDate. Waltham, MA: UpToDate; September, 2016;
                6. Sripathi N. Periodic Paralyses. Medscape Reference. March 24, 2016; https://emedicine.medscape.com/article/1171678-overview.

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