Key takeaways

  • Hereditary angioedema (HAE) is a genetic condition that can cause swelling in various parts of the body, such as the hands, face, and throat. In some cases, an HAE attack can be life threatening if a person does not receive treatment quickly.
  • While there is no cure for HAE, several medications are available to treat acute attacks and help prevent future attacks.
  • Early testing and diagnosis can allow people to begin treatment sooner and reduce the chances of complications.

Hereditary angioedema (HAE) is a rare condition that causes repeated episodes of swelling in the skin and mucous membranes (the lining of some organs and other structures in the body).

The swelling may affect any of the following body parts:

  • hands and feet
  • face (commonly the lips and eyes)
  • genitals
  • buttocks
  • tongue
  • throat

HAE may affect about 1 to 2 in 100,000 people worldwide, but the true number of cases is not well-documented. Reasons for this may include the limited awareness of HAE and the similarity of its symptoms to those of other conditions.

HAE is a genetic condition that often passes down from one generation to the next. A child may inherit HAE from a parent.

In other cases, the condition may result from a spontaneous (random) mutation at the time of conception. This mutation affects the gene responsible for producing a protein called C1 inhibitor.

In this article, we discuss HAE in more detail, including its causes, symptoms, and treatment.

There are two main types of HAE: type 1 and type 2. The third type, HAE with normal C1 inhibitor, is rare and not yet fully understood.

Type 1 HAE

Type 1 HAE accounts for nearly 85% of all cases. Type 1 occurs when a person has low levels of C1 inhibitor in their blood.

Type 2 HAE

Type 2 HAE accounts for 15% of all cases. In type 2 HAE, a person’s C1 inhibitor level is normal or close to normal, but the protein does not work as it should.

HAE with normal C1 inhibitor

HAE with normal C1 inhibitor, also known as estrogen-dependent or type 3 HAE, occurs in a very small number of people. Those living with this type of HAE experience symptoms of the condition, but they have normal C1 inhibitor levels, and the protein is fully functional. This type of HAE affects more females than males.

The primary cause of HAE is a genetic mutation that affects the production or function of C1 inhibitor protein.

In most cases, a child inherits the mutation from a parent. Children have a 50% chance of inheriting HAE if one of their biological parents has it.

However, in up to 25% of cases, the mutation happens spontaneously at the time of conception. A person who has a spontaneous mutation can then pass the genetic trait to their children.

Type 3 HAE does not result from a C1 inhibitor mutation. Instead, research has identified an association between HAE episodes and an increase in estrogen levels due to pregnancy or the use of birth control pills, among other factors.

The symptoms of the three main types of HAE are the same or similar. Swelling of the skin most commonly occurs in areas of the body such as the:

  • face
  • hands
  • arms
  • feet
  • legs
  • genitals
  • buttocks
  • airway

Swelling can cause loss of function in the affected area of the body, as well as pain and changes in physical appearance. The effects of an HAE attack typically go away within 2 to 5 days without needing treatment.

However, swelling that affects the throat can become a life threatening emergency that requires immediate medical attention.

A person might also experience swelling in the abdomen, which can cause additional symptoms such as pain, diarrhea, and vomiting. In some cases, healthcare professionals may mistake angioedema of the abdomen for an abdominal condition that requires surgery, such as appendicitis or pancreatitis.

Symptoms of HAE typically appear for the first time before the age of 13 years. The symptoms may become more severe as a person gets older.

Sometimes, a person may experience an episode of symptoms in response to a trigger, such as emotional stress or physical trauma. At other times, a person may experience an episode with no known cause.

Review the interactive guide below to learn about HAE testing and treatment.

HAE symptoms can be life threatening without proper treatment. However, most deaths related to HAE occur in people who have not received a diagnosis. Early testing and diagnosis can allow people to start treatment sooner, and effective treatment may reduce the chances of HAE complications.

Research on the life span of people with HAE has shown mixed results.

In one 2022 study in Brazil, researchers investigated the deaths of 75 people, 10 of whom had a diagnosis of HAE before they died. For the other 65 people, medical professionals determined after their deaths that they had HAE. In 39 of those 75 people, medical professionals declared that the cause of death was laryngeal edema, which can occur in HAE.

The researchers found that life span was 20 years shorter among the people who died from laryngeal edema than among those who died from other causes.

However, in a 2020 study that included data from 1,113 people with type 3 HAE in Italy, researchers found no significant difference between the life span of those people and that of the general population.

While further research on life expectancy in HAE is necessary, effective treatment, including management of acute HAE attacks, may allow many people to live typical, active lives.

HAE is a rare genetic condition that causes swelling in various areas of the body. Swelling that affects the throat can be life threatening if a person does not receive prompt treatment. Swelling in the abdomen can cause gastrointestinal symptoms such as pain, diarrhea, and vomiting.

Medications are available to treat individual HAE attacks and to help prevent future attacks. In some cases, the symptoms of an attack may resolve within a few days, even without treatment. A person should work with their doctor to get a proper diagnosis and create an effective treatment plan.