Hereditary Angioedema

Inhibiting Plasma Kallikrein for Hereditary Angioedema Prophylaxis

“…T h e ne w e ngl a nd jou r na l o f m e dicine H ereditary angioedema with C1 inhibitor deficiency is a rare genetic disease that is characterized by recurrent swelling episodes, typically affecting the subcutaneous or submucosal tissues of the hands and feet, abdomen, face, larynx, or genitourinary tract. 1 Swelling of the larynx can be life-threatening because of the risk of asphyxiation. 2 The disease is caused by a deficiency or dysfunction of C1 inhibitor, a key regulator of the complement, coagulation, and kallikrein-kinin cascades.…”

The functional promoter F12‐46C/T variant predicts the asymptomatic phenotype of C1‐INH‐HAE

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Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE, OMIM 106100) is a rare autosomal dominant disease with few cases of homozygous mutations reported in consanguineous patients, characterized by swelling of the face, lips, tongue, larynx, abdomen, genitalia or extremities. 1,2 It is caused by mutations in the SERPING1 gene, which codes for C1-INH, resulting in low levels of C1-INH (C1-INH-HAE type I, 85% of cases) or normal levels of nonfunctional C1-INH (C1-INH-HAE type II, 15% of cases). 1-3 In addition to C1-INH-HAE, other types of HAE include F12-HAE, PLG-HAE and ANGPT1-HAE, which are caused by specific mutations in the factor XII (F12) gene, plasminogen (PLG) gene, and angiopoietin-1 (ANGPT1) gene, respectively.

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“…To the Editor, Hereditary angioedema due to C1 inhibitor deficiency (C1-INH-HAE, OMIM 106100) is a rare autosomal dominant disease with few cases of homozygous mutations reported in consanguineous patients, characterized by swelling of the face, lips, tongue, larynx, abdomen, genitalia or extremities. 1,2 It is caused by mutations in the accounts for a more severe disease phenotype, the need for longterm prophylaxis, and earlier disease onset. 3,[5][6][7][8] However, only a small proportion of the variance can be predicted with the SERPING1 gene mutation type, and even in families with several affected members sharing the same mutation, differences in disease severity are well known, and by some estimations, up to 14% of carriers of the SERPING1 gene mutation remain asymptomatic throughout their entire life.…”

The complement and contact activation systems: partnership in pathogenesis beyond angioedema

“…38 HAE is a debilitating episodic multisystem disease caused by mutations in the complement protein, C1-INH, which is the major regulator of both the classical pathway of complement as well as the enzymes of the contact activation system that leads to the generation of bradykinin. [39][40][41][42][43][44] If the swelling involves the larynx or causes airway obstruction, the disease can be fatal due to asphyxiation. Because it accounts for only 2% of all angioedema cases (i.e.…”

“…[42][43][44] There are several types of hereditary angioedema (HAE): Type I, represents 85% of the cases and is due to low antigenic as well as functional levels of C1-INH ( Table 2). This is largely due to a mutation involving the Arg-444 of the P-1 site of the reactive center of the C1-INH gene 39,40 ; Type II HAE, affects approximately 15% of patients and is due to the presence of non-functional C1-INH although the antigenic level may be normal. Type III is a rare disease, which appears to affect primarily female patients.…”