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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.〔(【引用サイトリンク】publisher=HAE Canada )〕 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.〔(【引用サイトリンク】publisher=HAE Canada )〕 This disorder affects approximately one in 10,000–50,000 people. HAE type I is primarily caused by a deficiency in blood proteins (C1 esterase inhibitors) which normally suppress activation of the complement system. The resultant over-stimulation of this system leads to the production of inflammatory anaphylatoxins, which affects the flow of body fluids between the vascular system and body tissues. This deficiency is responsible for approximately 80-85% of cases. HAE type II is a less frequently encountered form of this disorder and accounts for 15-20% of cases. In this type, atypical C1-inhibitor proteins are produced which are less capable of suppressing activation of the complement system. Like HAE type I, this results in over-stimulation of this system. HAE type III is rare and has only been documented recently. Unlike types I and II, this form does not appear to be connected with C1-inhibitor deficiency. This type mainly affects females and appears to be influenced by contact with estrogens and also by hormone replacement therapy (e.g. oral contraceptives). Its pathogenesis is credited to increased activity of the enzyme kininogenase, which leads to rise in the levels of bradykinin. Other patients with type III HAE have alterations in gene F12, which encodes a protein which participates in blood coagulation.〔(【引用サイトリンク】publisher=HAE UK )〕 Some patients with type III HAE have a mutation in the F12 gene which produces a protein involved in blood clotting.〔(III hereditary angioedema: defined, but not understood. Kaplan A. Ann Allergy Asthma Immunol. 2012 Sep;109(3):153-4. doi: 10.1016/j.anai.2012.07.007. No abstract available. )〕 The underlying cause of HAE is attributed to autosomal dominant inheritance of mutations in the C1 inhibitor (C1-INH gene or SERPING1 gene),〔(C1 inhibitor hereditary angioedema. Kittisupamongkol W. Am J Med. 2009 May;122(5):e7; author reply e9. doi: 10.1016/j.amjmed.2008.11.011. No abstract available. )〕〔Colobran, Roger; Lois, Sergio; de la Cruz, Xavier; Pujol-Borrell, Ricardo; Hernández-González, Manuel; Guilarte, Mar. Clinical Immunology. Feb2014, Vol. 150 Issue 2, p143-148. 6p. DOI: 10.1016/j.clim.2013.11.013. :〕 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.〔Madsen, Flemming; Attermann, J&phgr;rn; Linneberg, Allan. Acta Dermato-Venereologica. 2012, Vol. 92 Issue 5, p475-479. 5p. DOI: 10.2340/00015555-1389.〕 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. The most common form of the disorder is HAE type I, which is the result of abnormally low levels of certain complex proteins in the blood (C1 esterase inhibitors), known as complements. They help to regulate various body functions (e.g., flow of body fluids in and out of cells). HAE type II is a more uncommon form of the disorder. It occurs as the result of the production of abnormal complement proteins and accounts for about 15-20% of this disorder.〔(of hereditary angioedema caused by C1-inhibitor deficiency: assessment and clinical management. Bork K, Davis-Lorton M. )〕 Type III is a very rare recently documented form: It predominantly affects females and it is influenced by exposure to estrogens or hormone replacement therapy (e.g. oral contraceptives and pregnancy) and is not associated with C1-INH deficiency. HAE type III is not due to C1 INH deficiency; it is linked to an increase in kininogenase activity leading to elevated levels of bradykinin.〔 Some patients with type III HAE have a mutation in the F12 gene which produces a protein involved in blood clotting.〔 == Pathogenesis == Because hereditary angioedema is an autosomal inheritable disease, there is no gender difference in transmission and both sexes are equally likely to receive the mutated gene from their parent(s). The figure below ''(courtesy of US National Library Of Medicine)'' depicts autosomal dominant transmission. Here, the father (individual A) with a mutated gene for HAE, has the disease while his wife (individual B) with 2 non-mutated copies of the C1 inhibitor gene and does not have the disease. The possibility of a cross between them gives the possibilities as shown: - two of their offspring will have the disease (HEA) while the others would not.;〔Ferraro, M. F.; Moreno, A. S.; Castelli, E. C.; Donadi, E. A.; Palma, M. S.; Arcuri, H. A.; Lange, A. P.; Bork, K.; Sarti, W.; Arruda, L. K. Allergy. Oct2011, Vol. 66 Issue 10, p1384-1390. 7p. 2 Diagrams, 1 Chart. DOI: 10.1111/j.1398-9995.2011.02658.x.〕〔Bafunno, Valeria; Bova, Maria; Loffredo, Stefania; Divella, Chiara; Petraroli, Angelica; Marone, Gianni; Montinaro, Vincenzo; Margaglione, Maurizio; Triggiani, Massimo. Annals of Human Genetics. Mar2014, Vol. 78 Issue 2, p73-82. 10p. DOI: 10.1111/ahg.12052.〕 The affected father who has HAE has mutation on one of his genes (C1-INH). Each one of his children, notwithstanding his/her sex, will have a 50% chance to inherit the mutated C1-INH gene from him. HAE is generally referred to as a “dominant” condition because it only takes a mutation in one of the two C1-INH genes in a carrier to cause the disease .〔(test indications and interpretations in patients with hereditary angioedema. Weiler CR, van Dellen RG. Mayo Clin Proc. 2006 Jul;81(7):958-72. Review. )〕〔()〕 The prevalence of HAE is relatively low - between 1 in every 10,000 to 1 in every 50,000 persons. Most of people with HAE acquire a C1 esterase inhibitor (C1-INH) mutation from one of their parents. A parent with HAE usually has a 50% probability of transmitting this condition on to one of his/her children of either sex as shown in the figure (HEA Inheritance). In occasions when HAE is not inherited and occurs in people with no previous history of it. This is because there are new impulsive or spontaneous changes in the sperm or egg cell that is responsible for this specific pregnancy. In a review of patients who do not have a history of HAE in their family, but who have relatively low levels of mutated C1-INH with persistent angioedema, 25% of new patients who had HAE had C1-INH changes that do not show signs of being inherited but rather new. The mutational changes in 1 or both of the carriers’ C1 inhibitor genes could have only occurred spontaneously, and just like in the example above, their offspring in this case will have a 50% probability of acquiring the mutated gene from either parent that has HAE. 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Hereditary angioedema」の詳細全文を読む スポンサード リンク
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