Rare Ophthalmology News

Disease Profile

Hereditary angioedema

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

All ages

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ICD-10

D84.1

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)

HAE; Hereditary angioneurotic edema; HANE;

Summary

Hereditary angioedema (HAE) is a disease characterized by recurrent episodes (also called attacks) of severe swelling of the skin and mucous membranes.[1] The age at which attacks begin varies, but most people have their first one in childhood or adolescence.[2] The frequency of attacks usually increases after puberty. Attacks most often affect 3 parts of the body:[2][3]

  • Skin the most common sites are the face (such as the lips and eyes), hands, arms, legs, genitals, and buttocks. Skin swelling can cause pain, dysfunction, and disfigurement, although it is generally not dangerous and is temporary.
  • Gastrointestinal tract the stomach, intestines, bladder, and/or urethra may be involved. This may cause symptoms such as nausea, vomiting, diarrhea, and abdominal pain.
  • Upper airway (such as the larynx and tongue) this can cause upper airway obstruction and may be life-threatening. The majority of attacks affecting the airway resolve before complete airway obstruction.

Attacks may involve one area of the body at a time, or they may involve a combination of areas. They always go away on their own but last from 2 to 4 days. While people with HAE have reported various triggers of attacks, emotional stress, physical stress, and dental procedures are the most commonly reported triggers.[2]

There are several types of HAE.[1] Types I and II are caused by mutations in the C1NH gene (also called the SERPING1 gene), which provides instructions for making the C1 inhibitor protein.[1][3] Type I is due to deficiency of C1 inhibitor, and type II is due to dysfunction of C1 inhibitor.[1] These types are also characterized by abnormal complement protein levels. Inheritance of types I and II is autosomal dominant, but not all people with a SERPING1 gene mutation will develop symptoms of HAE. A third type is called HAE with normal C1 inhibitor. This type is characterized by normal C1 inhibitor and normal complement protein levels, and usually begins in adulthood.[4] While some cases of type III are due to mutations in the F12 gene, in other cases the cause is not yet known.[1][5] The inheritance of this form is also thought to be autosomal dominant.[4]

Management of HAE involves treatment of sudden (acute) attacks and preventing attacks (prophylaxis).[3] Treatment for acute attacks in types I and II includes replacement with C1 inhibitor concentrates, a kallikrein inhibitor, or fresh-frozen plasma (by infusion).[3] Sudden attacks involving the upper airway may involve intubation if stridor or signs of respiratory distress are present.[4] HAE with normal C1 inhibitor levels is treated similarly, however C1 inhibitor infusion is not effective. Prophylaxis may involve regular injections of C1 inhibitor concentrates, long-term androgen (male hormone) therapy, or antifibrinolytics.[3][6]

The long-term outlook varies depending on the frequency and location of attacks, and the severity of attacks in each person. Attacks generally continue throughout life, but the frequency of attacks can be significantly reduced with therapy.[2]

Symptoms

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
Angioedema
0100665
5%-29% of people have these symptoms
Abdominal pain
Pain in stomach
Stomach pain

[ more ]

0002027
Ascites
Accumulation of fluid in the abdomen
0001541
Facial edema
Facial puffiness
Facial swelling

[ more ]

0000282
Intestinal edema
0005225
Intestinal obstruction
Bowel obstruction
Intestinal blockage

[ more ]

0005214
Laryngeal edema
0012027
Percent of people who have these symptoms is not available through HPO
Abnormality of the larynx
0001600
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Autosomal dominant inheritance
0000006
Autosomal recessive inheritance
0000007
Axonal degeneration
0040078
Diarrhea
Watery stool
0002014
Erythema
0010783
Peripheral axonal neuropathy
0003477
Pharyngeal edema
Throat swelling
0011855
Vomiting
Throwing up
0002013

Diagnosis

Making a diagnosis for a genetic or rare disease can often be challenging. Healthcare professionals typically look at a person’s medical history, symptoms, physical exam, and laboratory test results in order to make a diagnosis. The following resources provide information relating to diagnosis and testing for this condition. If you have questions about getting a diagnosis, you should contact a healthcare professional.

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

        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 Hereditary angioedema. This website is maintained by the National Library of Medicine.
        • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

          In-Depth Information

          • 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 Hereditary angioedema. Click on the link to view a sample search on this topic.

            Press Releases

            • The U.S. Food and Drug Administration (FDA) has recently approved Cinryze, Berinert and Kalbitor in the United States to protect people with hereditary angioedema (HAE). Click on the links above to read the FDA press releases related to these medications.

              References

              1. Cicardi M, Zuraw B. Hereditary angioedema: Pathogenesis and diagnosis. UpToDate. Waltham, MA: UpToDate; January 15, 2018; https://www.uptodate.com/contents/hereditary-angioedema-pathogenesis-and-diagnosis.
              2. Cicardi M, Zuraw B. Hereditary angioedema: Epidemiology, clinical manifestations, exacerbating factors, and prognosis. UpToDate. Waltham, MA: UpToDate; November 20, 2017; https://www.uptodate.com/contents/hereditary-angioedema-epidemiology-clinical-manifestations-exacerbating-factors-and-prognosis.
              3. Frank MM. Hereditary Angioedema. Medscape Reference. March 16, 2018; https://emedicine.medscape.com/article/135604-overview.
              4. Wu E, Frank MM. Hereditary angioedema with normal C1 inhibitor. UpToDate. Waltham, MA: UpToDate; August 18, 2017; https://www.uptodate.com/contents/hereditary-angioedema-with-normal-c1-inhibitor.
              5. Hereditary angioedema. Genetics Home Reference (GHR). 2009; https://ghr.nlm.nih.gov/condition/hereditary-angioedema. Accessed 1/24/2011.
              6. Cicardi M, Zuraw B. Hereditary angioedema: General care and long-term prophylaxis. UpToDate. Waltham, MA: UpToDate; October 25, 2017; https://www.uptodate.com/contents/hereditary-angioedema-general-care-and-long-term-prophylaxis.