Hereditary angioedema

Title

Other Names:

HAE; Hereditary angioneurotic edema; HANE; HAE; Hereditary angioneurotic edema; HANE; Deficiency of C1 esterase inhibitor; Hereditary angioedema type 1; Angioedema, hereditary See More

Summary Summary

Hereditary angioedema (HAE) is an immune disorder characterized by recurrent episodes of severe swelling. The most commonly affected areas of the body are the limbs, face, intestinal tract, and airway.^[1] HAE is caused by low levels or improper function of a protein called C1 inhibitor which affects the blood vessels.^[2] This condition is inherited in an autosomal dominant pattern.^[1]

There are three types of HAE, types I, II, and III. The types can be distinguished by their underlying causes and levels of C1 inhibitor in the blood. Type I and II are caused by mutations in the SERPING1 gene. Some cases of type III are associated with mutations in the F12 gene. Other genes are likely to be identified as the cause of other cases of HAE type III.^[1]

Last updated: 5/25/2011

Symptoms Symptoms

Hereditary angioedema is characterized by recurrent episodes of severe swelling (angioedema). The most commonly involved areas of the body are the limbs, face, intestinal tract, and airway. While minor trauma or stress may trigger an attack, swelling often occurs without a known trigger. Episodes involving the intestinal tract cause severe abdominal pain, nausea, and vomiting. Swelling in the airway can restrict breathing and lead to life-threatening obstruction of the airway. About one-third of people with this condition develop a non-itchy rash called erythema marginatum during an attack.^[1]

Symptoms of hereditary angioedema typically begin in childhood and worsen during puberty. Untreated individuals may have an attack every 1 to 2 weeks. Most episodes last 3 to 4 days. The frequency and duration of attacks vary greatly among individuals with hereditary angioedema, even among those in the same family.^[1]

Last updated: 1/24/2011

The Human Phenotype Ontology (HPO) provides the following list of features that have been reported in people with this condition. Much of the information in the HPO comes from Orphanet, a European rare disease database. If available, the list includes a rough estimate of how common a feature is (its frequency). Frequencies are based on a specific study and may not be representative of all studies. You can use the MedlinePlus Medical Dictionary for definitions of the terms below.

Signs and Symptoms	Approximate number of patients (when available)
Angioedema	Very frequent (present in 80%-99% of cases)
Ascites	Occasional (present in 5%-29% of cases)
Facial edema	Occasional (present in 5%-29% of cases)
Intestinal edema	Occasional (present in 5%-29% of cases)
Intestinal obstruction	Occasional (present in 5%-29% of cases)
Laryngeal edema	Occasional (present in 5%-29% of cases)
Abnormality of the larynx	-
Autoimmunity	-
Autosomal dominant inheritance	-
Diarrhea	-
Erythema	-
Peripheral axonal neuropathy	-
Pharyngeal edema	-
Vomiting	-

Last updated: 5/8/2017

Diagnosis 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 Treatment

Medical treatment of hereditary angioedema (HAE) consists of preventing attacks and managing acute attacks once they occur. During attacks, patients may require respiratory support. They also may require large amounts of intravenous fluids to maintain hemodynamic stability.^[3]

Until recently, no effective agent for acute attacks existed in the United States. Now, however, several agents have been approved, and others are in the midst of the U.S. Food and Drug Administration (FDA) approval process.^[3]

In October 2008, the US FDA approved the use of C1-INH (Cinryze) for prophylaxis to prevent attacks. In October 2009, the FDA approved C1-INH (Berinert) for the treatment of acute abdominal and facial angioedema attacks in adolescents and adults with HAE.In December 2009, ecallantide (Kalbitor), a kallikrein inhibitor, was approved for the treatment of acute attacks.^[3]^[4] In August 2011, the FDA approved Firazyr (icatibant) Injection for the treatment of acute attacks in people ages 18 years and older. Firazyr can be self-administered through an injection in the abdominal area so patients can treat themselves when they realize they are having an HAE attack.^[5]

An article from the eMedicine Journal provides more detailed information on these medications and other methods of treating HAE at the following link. You may need to register to view the article, but registration is free.
http://emedicine.medscape.com/article/135604-treatment

The US Hereditary Angioedema Association also provides additional information about treatment of HAE.
http://www.haea.org/treating-hae/treatments/

Orphanet, a database dedicated to information on rare diseases and orphan drugs, provides guidelines regarding emergency management of hereditary angioedema at the following link.
http://www.orpha.net/consor/cgi-bin/Disease_Emergency.php?lng=EN&stapage=FICHE_URGENCE_A1

Last updated: 11/11/2011

Management Guidelines

The NORD Physician Guide for Hereditary angioedema was developed as a free service of the National Organization for Rare Disorders (NORD) and it's medical advisors. The guides provide a resource for clinicians about specific rare disorders to facilitate diagnosis and treatment of their patients with this condition.
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.

C1 esterase inhibitor (human) (Brand name: Cinryze®) - Manufactured by ViroPharma Incorporated
FDA-approved indication: Routine prophylaxis against angioedema attacks in patients with Hereditary Angioedema (HAE)
National Library of Medicine Drug Information Portal
Icatibant (Brand name: Firazyr) - Manufactured by Shire Orphan Therapies
FDA-approved indication: Treatment of acute attacks of hereditary angioedema in adults 18 years of age and older
National Library of Medicine Drug Information Portal
Medline Plus Health Information
Ecallantide (Brand name: Kalbitor) - Manufactured by Dyax Corp
FDA-approved indication: Treatment of acute attacks of hereditary angioedema (HAE) in patients 12 years of age and older
National Library of Medicine Drug Information Portal
C1-esterase inhibitor (recombinant) (Brand name: Ruconest) - Manufactured by Pharming N.V.
FDA-approved indication: Treatment of acute attacks of hereditary angioedema (HAE) in adult and adolescent patients.
National Library of Medicine Drug Information Portal

Do you have updated information on this condition? Let us know.

Research Research

Research helps us better understand diseases and can lead to advances in diagnosis and treatment. This section provides resources to help you learn about medical research and ways to get involved.

Clinical Research Resources

ClinicalTrials.gov lists trials that are studying or have studied Hereditary angioedema. Click on the link to go to ClinicalTrials.gov to read descriptions of these studies.

Please note: Studies listed on the ClinicalTrials.gov website are listed for informational purposes only; being listed does not reflect an endorsement by GARD or the NIH. We strongly recommend that you talk with a trusted healthcare provider before choosing to participate in any clinical study.

Organizations Organizations

Nonprofit support and advocacy groups bring together patients, families, medical professionals, and researchers. These groups often raise awareness, provide support, and develop patient-centered information. Many are the driving force behind research for better treatments and possible cures. They can direct people to research, resources, and services. Many groups also have experts who serve as medical advisors. Visit their 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

HAEi – International Patient Organization for C1 Inhibitor Deficiencies (HAEi)
Kirstinelundsvej 7
DK-8660 Skanderborg
Denmark
E-mail: info@haei.org
Website: http://haei.org/hae/what-is-hae/
US Hereditary Angioedema Association, Inc.
Seven Waterfront Plaza
500 Ala Moana Blvd., Suite 400
Honolulu, HI 96813
Telephone: 866-798-5598
E-mail: info@haea.org
Website: http://www.haea.org

Do you know of an organization? Send us your suggestions.

Living With Living With

Living with a genetic or rare disease can impact the daily lives of patients and families. These resources can help families navigate various aspects of living with a rare disease.

Genetics Resources

To find a medical professional who specializes in genetics, you can ask your doctor for a referral or you can search for one yourself. Online directories are provided by GeneTests, the American College of Medical Genetics, and the National Society of Genetic Counselors. If you need additional help, contact a GARD Information Specialist. You can also learn more about genetic consultations from Genetics Home Reference.

Financial Resources

The Assistance Fund provides various services, including education and financial aid, to help patients with a chronic or serious illness cover the cost of FDA-approved medications. Patients must be U.S citizens or permanent residents.

Learn More 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

Genetics Home Reference (GHR) contains information on Hereditary angioedema. This website is maintained by the National Library of Medicine.
MedlinePlus was designed by the National Library of Medicine to help you research your health questions, and it provides more information about this topic.
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.

News & Events News & Events

NCATS Co-Sponsored Conferences

Hereditary Angioedema (HAE) Conference Friday, September 19, 2014 - Saturday, September 20, 2014
Location: San Diego, CA
Description: Anticipated goals and use of results: 1) Organize and conduct a conference that is thematically focused on growing and extending knowledge in HAE; and which become progressively more ambitious over time, reflecting the anticipated advances in research. 2) Identify topics and speakers that will clarify the most promising avenues of investigation, organize the conference in a manner that will optimally support communication between all participants, communicate the resulting discussions to the broader scientific, patient, and pharmaceutical communities. 3) Provide a supportive and constructive forum for young investigators, including female and minority scientists, to present their work and interact with more senior investigators. 4) Increase interest and awareness of HAE research among the wider research community particularly among young investigators in order to recruit new investigators into the field. 5) Ensure equal representation and access of women and underrepresented minority participants.

Contact: Nancy Coulter,(301) 496-1886, ncoulter@niaid.nih.gov

Co-funding Institute(s): National Institute of Allergy and Infectious Diseases, Office of Rare Diseases Research

GARD Answers GARD Answers

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Are there medications available to treat hereditary angioedema? See answer

Have a question? Contact a GARD Information Specialist.

References References

Hereditary angioedema. Genetics Home Reference (GHR). 2009; http://ghr.nlm.nih.gov/condition/hereditary-angioedema. Accessed 1/24/2011.
Dugdale DC, Henochowicz SI. Hereditary angioedema. MedlinePlus. 2010; http://www.nlm.nih.gov/medlineplus/ency/article/001456.htm. Accessed 1/24/2011.
Frank MM. Hereditary Angioedema: Treatment & Medication. eMedicine. 2010; http://emedicine.medscape.com/article/135604-treatment. Accessed 1/24/2011.
HAE Treatments. US Hereditary Angioedema Association. http://www.haea.org/treating-hae/treatments/. Accessed 1/24/2011.
FDA News Release. U.S. Food and Drug Administration. August 25, 2011; http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm269616.htm. Accessed 11/11/2011.