What Causes HAE?

There are two subtypes of HAE based on the underlying genetic defect in the control of the blood protein C1-Estrase Inhibitor (C1-INH) – and a third type of HAE with Normal C1-INH.


HAE Type 1

Representing approximately 80 to 85% of HAE cases, people with HAE Type I have levels of the C1-Inhibitor protein that are considerably below normal due to a defective gene on chromosome 11. There is usually a family history of HAE, but a number of cases are due to a spontaneous mutation of the gene.



HAE Type II makes up approximately 15 to 20% of hereditary angioedema cases. People with HAE Type II have adequate or even elevated levels of the C1-Inhibitor protein, however, it does not function properly. Symptoms and treatment are the same as with HAE Type I.

Normal C1

HAE with Normal C1

People affected by HAE with Normal C1-INH can experience swelling similar to Types I & II. To date, scientists have found mutations in 5 genes that may be associated with HAE Normal C1-INH: Factor XII, Plasminogen, Angiopoietin-1, Kininogen-1, and Myoferlin. Scientists are continuously looking for other genetic mutations that cause HAE.

The vast majority of people with HAE have a defect in the gene that controls a blood protein called C1-Inhibitor. This defect causes a biochemical imbalance that produces swelling. HAE is also known as C1-Inhibitor Deficiency – Type I and Type II. People diagnosed as having HAE with Normal C1-Inhibitor experience swelling symptoms generally similar as seen in Type I and II. Globally, scientists are researching how to better understand the underlying genetic and biochemical causes and find treatments for the very important members of our community who suffer from HAE with Normal C1-Inhibitor.

HAE is hereditary and children have a 50% chance of inheriting HAE if one of their parents has the condition. However, the absence of a family history does not rule out the diagnosis of HAE, as scientific reports indicate that as many as 25% of HAE cases result from a spontaneous mutation of the C1-Inhibitor gene at conception. Children of people with HAE may also inherit the condition.