Disease name

유전성 혈관부종
Hereditary angioedema

Marker gene

Gene symbol	Chromosome location	Protein name
F12	5q35.3	Coagulation factor XII
SERPING1	11q12.1	Plasma protease C1 inhibitor

Prevalence

1-9 / 100 000

Inheritance

상염색체 우성

Age of onset

다양함

ICD 10 code

D84.1

MIM number

106100

610618

Synonym

Familial angioneurotic edema

HAE

Hereditary angioneurotic edema

Hereditary bradykinine-induced angioedema

Hereditary non histamine-induced angioedema

Summary

Hereditary angioedema (HAE) is a genetic disease characterized by the occurrence of transitory and recurrent subcutaneous and/or submucosal edemas resulting in swelling and abdominal pain. Prevalence has been estimated at 1/100,000. Onset may occur at any age but is most common during childhood or adolescence. Patients present with white, circumscribed nonpruritic edemas that remain for a period of 48 to 72 hours and recur with variable frequency. The edemas may involve the digestive tract resulting in a clinical picture similar to that seen in intestinal occlusion syndrome, sometimes associated with ascites and hypovolemic shock. Laryngeal edema can be life-threatening with a risk of death of 25% in the absence of appropriate treatment. Dental procedures are a triggering factor for laryngeal edema. Edemas of the face are a risk factor for laryngeal involvement. Three types of HAE have been described. HAE types I and II are caused by anomalies in the SERPING1 gene (11q12-q13-1) encoding the plasma protease C1 inhibitor (C1-INH): type I is caused by deletion or by expression of a truncated transcript leading to a quantitative defect in C1-INH; type II is caused by point mutations leading to a qualitative defect in C1-INH. Transmission is autosomal dominant and most cases involve heterozygotes. The edemas are triggered by increased permeability of the blood vessels in response to elevated levels of bradykinin as a result of the C1-INH deficiency. HAE type III predominantly involves females, with the use of estrogen-containing oral contraceptives and pregnancy being precipitating factors. HAE type III is not caused by C1-INH deficiency but is associated with an increase in kininogenase activity leading to elevated levels of bradykinin. Some cases are associated with coagulation factor XII (Hageman factor; F12) gain-of-function mutations but other genetic anomalies remain to be identified. Diagnosis of HAE types I and II relies on measurement of C4 concentrations and on quantitative and functional analysis of C1-INH. Diagnosis of HAE type III revolves around recognition of the clinical picture. C4 and C1-INH levels are normal. Measurement of kininogenase activity and analysis for mutations in the F12 gene may be proposed. The differential diagnosis should include acquired angioedema (see this term), intestinal occlusion syndrome and histamine-induced angioedema (of allergenic or nonallergenic origin) generally associated with urticaria. Screening of family members, including asymptomatic individuals, is recommended. Corticosteroid treatments are not effective. Tranexamic acid should be used to treat moderate episodes, and acute attacks (involving a laryngeal edema) should be treated with subcutaneous icatibant (a bradykinin receptor antagonist) or intravenous administration of C1-INH concentrate. Prophylactic treatment with tranexamic acid or danazol may be proposed for patients with frequent episodes. The vital prognosis is good for patients who have been diagnosed and have access to the proper treatment in case of a laryngeal edema. However, significant morbidity may be associated with digestive involvement resulting in pain and patients becoming bedridden for at least three days following the episode.