Hereditary angioedema (HAE)

Hereditary angioedema (HAE) is an inherited disorder caused by a specific mutation in the affected person’s genetic code. The gene in question is located on chromosome 11 and is responsible for the production of an enzyme known as C1-esterase inhibitor (C1-INH). C1-INH is an important protein that regulates a variety of metabolic processes in the body.

As a result of the underlying genetic mutation, persons suffering from HAE either produce too little C1-INH or a type of C1-INH that does not function properly. One of the effects of C1-INH is to prevent an excessive production of bradykinin in response to inflammation, coagulation reactions and other processes in the body. Bradykinin acts to increase the permeability of the blood vessel walls.

  • are recurrent
  • last for several hours or days, and
  • then spontaneously resolve 

The genetic mutation affecting the synthesis of C1-INH is subject to autosomal dominant inheritance. This means that the child of an affected parent has a 50% chance of inheriting the disease. The inheritance is completely independent of the sex of the child or of the affected parent. However, not every person with this kind of angioedema has a positive family history: in about one in four patients, the mutation responsible for HAE occurs spontaneously in offspring of a family with no known previous cases of the disease. This type of mutation is known as a “new” or “de novo mutation”.

At the present time, three distinct types of HAE have been characterized. They differ with respect to their respective causes and symptoms.

  • Typ I HAE: This is the most common form of HAE, affecting 80-85% of patients. In type 1 HAE, affected persons produce too little C1-INH.
  • Typ II HAE: In this type, which affects about 15-20% of patients, C1-INH is produced but does not function correctly.
  • Typ III HAE: This type is extremely rare and its exact causes are not yet completely understood. The mutation responsible for this type of HAE affects a different gene. Type III HAE is found predominantly in women and is usually associated with an increased oestrogen level, such as during pregnancy or in women taking oral contraceptives.  

HAE is a rare but important disease entity. Worldwide, it is estimated that about 2-4/100,000 persons are affected. In Europe, 10,000 to 50,000 persons suffer from HAE; of these about 1,200 live in Germany. Experts, however, suspect that the number of unrecognised cases may be much higher. This is because the symptoms of HAE often resemble those of other more common diseases and the general familiarity with this disease is low. The vast majority of HAE patients experience their first swelling attack before the age of 30 years, sometimes even in infancy. Men and women suffer from the disease in about equal numbers.