Hereditary Angioedema, or HAE, is a very rare and potentially life-threatening genetic condition that occurs in about 1 in 10,000 to 1 in 50,000 people and involves recurrent attacks of severe swelling (angioedema) in various parts of the body, including the hands, feet, genitals, stomach, face and/or throat. Swelling in the airway can restrict breathing and be fatal. Episodes may be triggered by physical trauma or emotional stress; however, swelling often occurs without a known trigger. Symptoms of HAE usually appear early in life, most often by age 13, and may increase in severity after puberty. Because HAE is so rare, it can take as long as a decade to obtain an accurate diagnosis after symptoms are first experienced.

When untreated, an HAE attack often lasts for three days, sometimes even longer, and many people with HAE experience three or more swelling attacks per month. The frequency and severity of attacks vary significantly among individuals, even among affected family members.

The vast majority of people with HAE have a genetic defect that causes a deficiency in the plasma protein called C1-Inhibitor. HAE is also seen in people who have normal levels of C1-Inhibitor, however, genetic defects in other genes cause their angioedema.

Type I

Type II

Normal C1 Inhibitor

Patients with Type I have low levels of C1-Inhibitor due to a defective gene on chromosome 11.

Patients 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.

Formally called Type III, HAE with Normal C1 Inhibitor patients have normal levels and function of C1-Inhibitor. Research has uncovered genetic defects in 3 other genes that cause HAE symptoms. These genes are Factor XII, Angiopoietin-1, and Plasminogen.

It runs in the family

HAE is called hereditary because the genetic defect is passed on in families.

A child has a 50 percent possibility of inheriting this disease if one of the parents has it. The absence of family history does not rule out the HAE diagnosis, however.

Scientists report that as many as 20 percent of HAE cases result from patients who had a spontaneous mutation of the C1-Inhibitor gene at conception. Consequently, these patients can pass the defective gene to their offspring.

A large number of patients report that their frequent and severe abdominal pain was inappropriately diagnosed as psychosomatic, resulting in a referral for psychiatric evaluation.

Unnecessary exploratory surgery has been performed on patients experiencing gastrointestinal edema, because abdominal HAE attacks mimic a surgical abdomen.

Before therapy became available, the mortality rate for airway obstruction was reportedly as high as 30 percent.