Causes and Types of 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.
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 HAE cases. People with 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.
People with HAE with Normal C1-Inhibitor levels and function can experience swelling generally similar to Types I and II. Scientists have found that defects in 3 other genes – Factor XII, Angiopoietin-1, and Plasminogen – cause HAE. There are commercial labs that can test for Factor XII mutations, but genetic sequencing for Angiopoietin-1 and Plasminogen are only available in a research setting. Scientists are continuing to look for other genetic mutations that cause HAE.