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Hereditary angioedema (HAE) is a rare condition that can cause sudden swelling in the face, hands, feet, stomach, genitals, or throat. Because HAE can look like more common health conditions, such as allergic reactions, it can be hard to diagnose.
HAE affects about 1 in 50,000 people. However, it’s hard to know the exact number because some people may go years without the right diagnosis.
Here’s more on HAE and why it’s considered a rare disease.
A rare disease is a condition that affects a small number of people. In the United States, a rare disease is defined as a medical condition, illness, or disorder that occurs in fewer than 200,000 people in the U.S.
In 2025, the U.S. population was about 342 million people. If around 1 in 50,000 people have HAE, that would be about 0.002 percent of Americans, or around 6,840 people in the U.S.
HAE is one of more than 10,000 rare diseases in the U.S. More than 30 million people in the U.S. are affected by rare diseases.
In other countries, a rare disease may be defined somewhat differently. For instance, in the European Union, a rare disease is defined as a condition that affects 5 out of 10,000 people or fewer. Some countries don’t have an official definition of a rare disease.
About 80 percent of rare diseases, including HAE, are genetic disorders. This means they’re caused by an abnormality or change in someone’s DNA. Many start in childhood.
Genetic mutations, or changes, can be inherited or develop during someone’s life. HAE is usually inherited, which is why most people with HAE have a family history of the disease.
The condition has an autosomal dominant pattern. This means it can be inherited from either parent and can develop if just one copy of the gene that causes HAE is passed down.
In about 25 percent of cases, people develop HAE because of a genetic change that isn’t inherited from a parent. That’s known as a spontaneous mutation.
People with HAE have repeated episodes of severe swelling. These episodes can affect the hands, feet, airways, genitals, or digestive tract. Swelling in the digestive tract can cause abdominal pain.
HAE symptoms are different for everyone. They depend on where the swelling happens. HAE can be life-threatening when the airways are affected, which can cause breathing to stop.
Researchers don’t fully understand how many people have HAE for several reasons. As a rare disease, there’s a lack of data on the condition. HAE can also have symptoms that look like other conditions. Because of this, there’s a risk of misdiagnosis.
Estimates of how common HAE is can vary, but all estimates show that it is very rare. One review of medical studies published in the International Archives of Allergy and Immunology estimated that HAE affects between 1 and 2 people out of every 100,000.
More recent research indicates that the rate of HAE may be more than 2 out of 100,000 (or 1 out of 50,000). Researchers are continuing to study how common this disease is to help make sure that people with HAE get the treatment they need.
One challenge in tracking the number of HAE cases is that there hasn’t been a specific diagnostic code for HAE in the U.S. Diagnostic codes are entered into medical records and used by health insurance companies and can provide valuable data for researchers.
It can also be hard to know how common HAE is because its symptoms can look like other types of angioedema, including allergic reactions to food, medication, insect bites or stings, or other substances.
Allergic angioedema can cause sudden swelling in the face, hands, feet, or genitals that can look like HAE. Similar to HAE, allergic angioedema can cause a life-threatening swelling of the throat and tongue, which can stop breathing and is a medical emergency.
However, allergic angioedema is treated with drugs such as antihistamines, corticosteroids, and epinephrine. These drugs don’t work for HAE. Allergic angioedema symptoms can also include hives and itchiness, which don’t happen with HAE.
In the U.S., 11 medications have been approved to treat HAE. Some of these drugs work by addressing abnormalities in the C1 inhibitor (C1INH) protein. This protein normally helps control parts of the immune system. When it is missing or doesn’t work properly, severe swelling can happen. HAE treatment focuses on preventing swelling attacks and treating attacks when they happen.
Symptoms of HAE can resemble other conditions. It’s frequently misdiagnosed or overlooked. When HAE isn’t accurately assessed, diagnosis is often delayed. Because of misdiagnosis and delayed diagnosis of HAE, researchers aren’t sure about the rate of HAE cases.
Research shows that an accurate diagnosis of HAE can take as long as 10 years. According to one study, less than 38 percent of people with HAE were accurately diagnosed within 1 to 3 years of first experiencing symptoms.
There are three types of HAE. About 85 percent of HAE cases are type 1, the most common type of HAE. In people with type 1 HAE, the body doesn’t produce enough C1INH protein. (HAE types are sometimes rendered with Roman numerals, such as type II for type 2.)
Type 2 HAE is the second most common type of HAE. People with type 2 HAE make enough C1INH protein, but it doesn’t work properly. Type 1 and type 2 HAE are caused by changes in the SERPING1 gene.
HAE with normal C1INH, originally called type 3 HAE, is the rarest form of HAE.
In these cases, C1INH protein is normal, but other factors lead to abnormal swelling. It’s sometimes known as HAE-nC1INH. The “n” indicates normal C1INH.
Type 3 HAE was first recognized in the year 2000. The condition is considered extremely rare. Researchers don’t fully understand the causes of HAE-nC1INH. Some people with type 3 HAE have various genetic mutations, but in other cases, no genetic changes have been found.
Genetic testing may be done to understand more about the genetic causes of a particular case of HAE.
HAE causes swelling in a different way than other types of angioedema. This is why treatments for severe swelling from allergic angioedema will not stop potentially life-threatening HAE swelling.
If you or your child is living with HAE, it’s important to understand which treatment option may be right for you. If you have any questions or concerns about your treatment plan for HAE, be sure to talk to your doctor and healthcare team.
New treatment options have become available in recent years. You may want to ask your doctor or HAE specialist whether any newer treatments may be right for you.
On myHAEteam, people share their experiences with hereditary angioedema, get advice, and find support from others who understand.
Have you talked to your doctor about what it means to live with a rare disease? Let others know in the comments below.
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