Hereditary angioedema

Hereditary angioedema (types I, II and III) (also known as “HAE”) is a rare, autosomal dominantly inherited blood disorder that causes episodic attacks of swelling that may affect the face, extremities, genitals, gastrointestinal tract and upper airways. Swellings of the intestinal mucosa may lead to vomiting and painful, colic-like intestinal spasms that may mimic intestinal obstruction. Airway edema may be life-threatening. Episodes may be triggered by trauma, surgery, dental work, menstruation, some medications, viral illness and stress; however, this is not always readily determined. This disorder affects approximately one in 10,000–50,000 people.

HAE type I primarily caused because of abnormally low concentration some complex blood proteins (C1 esterase inhibitors), also called complements. These help to control various body functions such as the flow of body fluids in and out of cells. It is responsible for approximately 80-85% of this disorder.

HAE type II is a more infrequent form of this disorder. It occurs due to the fabrication of atypical complement proteins and accounts for about 15-20% of this disorder . Type III is not common and was documented recently. This type mainly afflicts females and it is influenced by contact with estrogens and also by hormone replacement therapy (e.g. oral contraceptives and pregnancy) and this is not connected with the deficiency of C1-INH.

HAE type III is not necessarily caused by C1-INH deficiency; it is credited to a rise in the action of the enzyme kininogenase’s and this then leads to rise in the levels of bradykinin. Some patients who have the type III HAE will have an alteration in the F12 gene and this produces a protein which participates in the clotting of blood . Some patients with type III HAE have a mutation in the F12 gene which produces a protein involved in blood clotting.

The underlying cause of HAE is attributed to autosomal dominant inheritance of mutations in the C1 inhibitor (C1-INH gene or SERPING1 gene), which is mapped to chromosome 11 (11q12-q13.1).To date there are over 300 known genetic mutations that result in a deficiency of functional C1 Inhibitor. 2-4 The majority of HAE patients have a family history; however, 25% are the result of new mutations. The low level of C1 inhibitor in the plasma leads to increased activation of pathways that release bradykinin, the chemical responsible for the angioedema due to increased vascular permeability, and the pain seen in individuals with HAE.