Hereditary angio-oedema with normal C1 inhibitor in a family with affected women and men

Abstract

Recurrent angio-oedema is a sign of various acquired and inherited disease entities, including hereditary angio-oedema types I and II that result from a genetic deficiency of C1 inhibitor, and a recently described type of dominantly inherited angio-oedema, which does not show a deficiency of C1 inhibitor. Until now, this new type of hereditary angio-oedema, designated as hereditary angio-oedema type III, has been assumed to be a disorder specific to females. We now describe a four-generation family with dominantly inherited angio-oedema and normal C1 inhibitor in which, in contrast to all previous observations, not only five female but also three male family members were clinically affected. One male patient was mainly affected following the intake of angiotensin-converting enzyme inhibitors. Our current observation leads to new considerations about the classification of hereditary angio-oedema with normal C1 inhibitor. Either hereditary angio-oedema with normal C1 inhibitor can be an entity affecting females predominantly, but not exclusively; in that case, men appear to have a much reduced chance of clinical manifestations. Alternatively, our present observation of hereditary angio-oedema with normal C1 inhibitor affecting both sexes may represent a new disease entity, presumably with a different underlying defect.

Hereditary angioedema with normal C1 inhibition

“…It has been reported that angiotensin-converting enzyme inhibitors can induce an exacerbation of symptoms in patients with HAE-C1-INH [16]. We observed a 60-year-old man from a family with HAE with normal C1-INH who has had arterial hypertension since age 30 and had four tongue swellings following treatments with captopril and enalapril [5]. The last episode occurred when the patient received only hydrochlorothiazide and metoprolol.…”

“…In two families, however, the existence of clinically unaffected male carriers has been deduced [2,3]. In 2006, we described a family with dominantly inherited angioedema and normal C1 inhibitor activity in which not only fi ve female but also three male family members were clinically affected [5]. Later, more male patients with HAE III were reported, among them were patients with HAE-FXII [8•,12•].…”

“…Because all 76 patients from the studies cited above were women, it was assumed that the clinical phenotype might be limited to the female sex. However, in 2006 we described a family with dominantly inherited angioedema and normal C1-INH, in which not only fi ve female but also three male family members were clinically affected [5]. Later on, a number of patients with HAE type III were reported [6,7,8•,9,10].…”

Angioedema: Diagnosis and treatment approaches

“…Bazı olgularda menarş öncesinde olup puberte sonrası ve/veya yüksek östrojen düzeyleriyle alevlenen AE tablosu görülürken, bazı olgularda düşük veya normal seviyedeki östrojen düzeylerinde bile AE görülebildiği bildirilmiştir [19][20][21] . Daha sonraları ise akrabalık bağı olan bazı erkek olgularda da görüldüğü saptanmıştır 22,23 . Tip 3 HAE'nın erkeklerden akrabalık bağı bulunan diğer erkek olgulara da geçişinin görülmesi nedeniyle otozomal dominant kalıtımlı olduğu ve penetransının düşük olması nedeniyle toplumdaki asemptomatik taşıyıcı kadınların sayısının az olmadığı düşünülmektedir.…”

Hereditary Angio-Oedema for Dermatologists

“…HAE with normal C1INH, formerly known as HAE type III, was initially documented only in women; however, it was later also reported in males [27]. In 2006, it was revealed that some of these families had mutations in the F12 gene encoding Hageman factor [28], and more recently mutations in the gene encoding angiopoietin-1 (ANGPT1) and the gene encoding plasminogen (PLG) have also been documented [29-34].…”