• Fabry Disease
• HAE (Hereditary Angioedema)
• MLD (Metachromatic Leukodystrophy)
• Sanfilippo Syndrome (MPS III)

• Hereditary Angioedema
  • Overview
  • Disease Process
  • Signs and Symptoms
  • Other Types of Angioedema
  • Diagnosis
  • Inheritance
  • Management
• Personal Stories
• News Articles
• Resources

Disease Process of Hereditary AngioedemaNext Topic

HAE is usually caused by an inherited deficiency in a protein called C1 esterase inhibitor (C1-INH). Normally, C1-INH functions to help your immune system fight off infections and to help other body systems control blood clotting and bleeding. In HAE, diminished amounts or defective C1-INH causes blood vessels to become permeable or “leaky,” leading to fluid buildup in body tissues. This buildup results in the HAE symptoms of skin swelling (edema), severe abdominal pain, vomiting, and potentially life-threatening swelling of the larynx.

Bradykinin: Instigator of HAE Attacks

An important instigator of HAE attacks that is related to C1-INH is a protein in your body called bradykinin. Normally, to help protect the body, bradykinin helps to control vasodilation (widening of blood vessels) and blood-vessel permeability (or “leakiness”). However, when C1-INH is deficient, bradykinin levels increase excessively, resulting in HAE attacks.

Types of HAE

Nearly all patients with HAE have C1-INH deficiency, which may result from decreased levels of functioning C1-INH, or from normal levels of defective, nonfunctioning C1-INH. There are three types of HAE, and type 1 is the most common.

• Type 1 HAE. Approximately 85% of HAE patients have type 1 HAE, in which levels of functionally active C1-INH are abnormally low.
• Type 2 HAE. Approximately 15% of patients have type 2 HAE, in which levels of C1-INH protein are normal or increased, but the protein itself is dysfunctional. Mutations are usually found in exon 8, an important region of the gene for proper function.
• Type 3 HAE. Type 3 HAE is rare and occurs predominantly in women. It is not associated with C1-INH deficiency, and is thought to be due to a mutation in the gene for a plasma protein involved in coagulation (coagulation factor XII). Type 3 HAE is sometimes associated with oral contraceptives or hormone replacement therapy (HRT).

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