Hereditary angioedema (HAE) is a rare but potentially life-threatening condition characterized by acute attacks of usually non-itching edema (swelling) of the face, larynx (airway), abdomen and extremities. The severity of the disease, as well as the frequency and location of HAE attacks, vary widely between individuals and throughout a patient’s life.
HAE is caused by lack of — or malfunctioning — C1-esterase inhibitor (C1-INH), the primary control protein of the so-called complement system that regulates inflammation and vascular permeability.
Clinical Hereditary Angioedema Symptoms
An attack of HAE is characterized by episodes of swelling that can affect many different regions of the body, including the extremities, face, larynx, gastrointestinal (GI) tract and genitourinary system.
The site at which an HAE attack occurs is variable between patients. The most common sites for an HAE attack include the skin, abdomen and larynx.
Swelling of the skin is non-pitting and non-erythematous, with ill-defined margins. It tends to spread and disfigure the affected site, depriving it of function. Symptoms of abdominal swelling include mild discomfort to severe pain accompanied by vomiting and/or diarrhea. Patients may also experience hypotension, with feelings of light-headedness and dizziness. HAE attacks involving the larynx are particularly serious as the swelling can impair breathing and lead to suffocation.
HAE attacks are frequently associated with prodromal symptoms that include rash, influenza-like symptoms, malaise, paresthesia, headache and abdominal discomfort.
The frequency with which patients experience attacks of HAE varies between individuals. The majority of patients have 6-11 attacks per year. The edema associated with an attack usually develops gradually over several hours, increasing slowly for 12-36 hours, before subsiding after 2-5 days.
The severity of an HAE attack can vary significantly. Some attacks can be mild and temporarily disfiguring due to swelling, whereas others can be life-threatening as a result of secondary effects of the edema, e.g. HAE of the larynx can impair breathing and lead to suffocation.
Hereditary Angioedema Causes
HAE is caused by a mutation in the gene that encodes a protein called C1-esterase inhibitor (C1-INH), which is present in blood and helps control inflammation and swelling. More than 150 different genetic mutations that can cause the symptoms of HAE have been identified to date.
Three different types of Hereditary Angioedema have been identified:
Type 1 (HAE-1)—85% of patients with HAE have a genetic mutation that leads to no C1-INH being produced
Type 2 (HAE-2)—15% of patients with HAE have a genetic mutation that leads to a dysfunctional C1-INH being produced
Type 3 (HAE-3)—an extremely rare form of HAE occurring mainly in women; C1-INH levels are normal, but the cause is yet to be fully understood.
In type 1 and type 2 HAE, C1-INH function is usually reduced to 5-30% of normal levels.
The symptoms of HAE are caused by the movement of plasma out of blood vessels, leading to fluid collecting (edema) in the deep tissue layers.
Hereditary Angioedema Prevalence
The prevalence of HAE has been estimated to range from 1 in 10,000 to 1 in 50,000. Males and females, and all ethnicities, are almost equally affected by HAE.
A child of an affected parent has a 50% chance of inheriting HAE. However, the condition is not inherited in all cases. In approximately 20% of all cases, HAE results from a spontaneous mutation of the C1-INH gene at conception.