Hereditary angioedema (HAE) is a rare genetic condition affecting between 1 in 10,000 and 1 in 50,000 people globally. It causes painful, severe swelling and usually targets the skin, throat, and abdomen. If left untreated, the swelling from HAE can be debilitating or even life-threatening.
What causes HAE?
Most cases of HAE are linked to mutations in the SERPING1 gene. This gene makes a blood protein called C1 esterase inhibitor. The C1 esterase inhibitor is part of the immune system. It’s involved in the biochemical reactions controlling the body’s inflammatory response.
Normally, C1 esterase inhibitor regulates the production of a hormone called bradykinin. Bradykinin increases the leakage of fluid from blood vessels into your body’s tissues. When C1 esterase inhibitor isn’t working properly, your body releases too much of the hormone. This can lead to swelling.
The mutations that cause HAE are usually inherited from a parent. The gene is dominant, which means one abnormal copy is enough to cause HAE. If you have the abnormal gene, your children have a 50 percent chance of inheriting it.
About 20 to 25 percent of HAE cases aren’t inherited. These cases arise from a random mutation that happens at conception. People with this spontaneous from of HAE can still pass it on to their children.
Types of HAE
There are three different types of HAE. The type depends on the genetic mutations underlying the condition and how it leads to inflammation.
This is the most common form of HAE, accounting for 85 percent of people with the condition. In type I HAE, SERPING1 mutations reduce C1 esterase inhibitor levels in the blood. This causes the body to make too much bradykinin, and leads to swelling attacks.
People with type 1 HAE have severe swelling attacks that can affect the:
The severity, frequency, and timing of attacks can be unpredictable and vary throughout a person’s life.
Type I attacks can be treated with medications on-demand at home or at a healthcare center. These medications are delivered by injection or intravenously. They include:
- C1 inhibitors (Cinryze, Berinert, Ruconest)
- bradykinin receptor blockers (Firazyr)
- enzyme inhibitors (Kalbitor)
Long-term or short-term preventive treatments using androgens or C1 inhibitors are also available. Your choice of preventive treatment depends on individual factors, such as your tolerance of side effects and the dosage required. Women may have negative reactions to androgen therapy and shouldn’t use it during pregnancy or breast-feeding. Even with preventive treatment, attacks can still happen.
Medications used to treat allergies, such as prednisone or antihistamines, generally don’t work against HAE.
Type II is the second most common form of HAE, making up about 15 percent of cases. Like type I HAE, it’s caused by a mutation in the SERPING1 gene. However, in type II HAE, an improperly functioning C1 inhibitor, not a lack of the protein, leads to inflammation and swelling episodes.
Type II HAE has the same symptoms and treatment options as type I.
Type III (HAE with normal C1 inhibitor)
Type III HAE is very rare. This type of HAE isn’t associated with abnormalities in the SERPING1 gene or C1 esterase inhibitor.
The causes of type III HAE aren’t fully understood. Sometimes it’s associated with a mutation in the F12 gene, which makes coagulation factor XII. Coagulation factor XII is a protein involved in blood clotting and inflammation. Swelling is linked to an overproduction of bradykinin caused by abnormalities in this protein.
Since the genetic explanation for HAE type III is still unclear, a family history of angioedema is usually required to diagnose it.
The symptoms of HAE type III are similar to HAE types I and II. However, some people with type III HAE tend to have more attacks of facial swelling. Type III HAE affects more women than men.