Hereditary angioedema with normal C1-inhibitor (HAE-nC1-INH) is a rare genetic disease with similar phenotype to HAE-C1-INH but different genetic background. Currently, 6 subtypes are recognized, based on the underlying mutations. Several aspects need further clarification. To assess clinical features of patients with genetically characterized HAE-nC1-INH from the North of Portugal. Retrospective assessment of clinical data from all patients with HAE-nC1-INH followed at a HAE Reference Center. A total of 41 patients were identified, 4 with no family history. The FXII mutation Thr328Lys (38 carriers) was the most prevalent. There were 3 new potentially disease-causing variants linked to HAE-nC1-INH identified (c.529+4A>G:FXII; Cys248*:Kininogen-1; and Arg261His:Plasminogen). The HAE-FXII cohort included 82% females and 71.8% symptomatic patients. Penetrance rate was significantly higher in females (81.3% vs 28.6%; = .012). A hormonal influence was observed in 96.2% of the symptomatic females, although 62.5% remained symptomatic after oral estrogen withdrawal. Trauma and dental procedures were frequent triggers (82.6% and 45.5%, respectively). Main locations were facial (described by 96%), lips (82.1%), and eyelids (64.3%). One patient reported erythema marginatum as prodrome. Plasma-derived C1-INH was effective as short-term prophylaxis in all treated patients, but only in 80% as on-demand treatment. Icatibant was effectively used on demand in 9 patients, but with relapses in 5 (57%). We described a large Portuguese series of patients with HAE-nC1-INH genetically characterized. Differences with others may contribute to improve current unmet needs and raise awareness of this rare disease. We highlighted the identification of 3 new variants (additional molecular studies are ongoing) and the report of erythema marginatum in HAE-nC1-INH.

中文翻译：

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C1 抑制剂正常的遗传性血管性水肿：15 个葡萄牙无关家族的临床和遗传特征

正常 C1 抑制剂遗传性血管性水肿 (HAE-nC1-INH) 是一种罕见的遗传性疾病，其表型与 HAE-C1-INH 相似，但遗传背景不同。目前，根据潜在的突变，可识别 6 种亚型。有几个方面需要进一步澄清。评估来自葡萄牙北部的具有基因特征的 HAE-nC1-INH 患者的临床特征。在 HAE 参考中心对所有 HAE-nC1-INH 患者的临床数据进行回顾性评估。总共确定了 41 名患者，其中 4 名没有家族史。FXII 突变 Thr328Lys（38 个携带者）是最常见的。发现了 3 个与 HAE-nC1-INH 相关的新的潜在致病变异（c.529+4A>G:FXII；Cys248*:Kininogen-1；和 Arg261His:纤溶酶原）。HAE-FXII 队列包括 82% 的女性和 71.8% 的有症状患者。女性的外显率显着较高（81.3% vs 28.6%；= .012）。在 96.2% 有症状的女性中观察到荷尔蒙的影响，尽管 62.5% 在口服雌激素停药后仍然有症状。外伤和牙科手术是常见的触发因素（分别为 82.6% 和 45.5%）。主要部位是面部（96%）、嘴唇（82.1%）和眼睑（64.3%）。一名患者报告边缘红斑是前驱症状。血浆衍生的 C1-INH 作为短期预防对所有接受治疗的患者均有效，但仅对 80% 的按需治疗有效。9 名患者按需有效使用艾替替班，但 5 名患者（57%）复发。我们描述了葡萄牙一系列具有 HAE-nC1-INH 基因特征的患者。与其他人的差异可能有助于改善当前未满足的需求并提高对这种罕见疾病的认识。我们重点介绍了 HAE-nC1-INH 中 3 个新变异的鉴定（更多分子研究正在进行中）以及边缘红斑的报告。