Recke Andreas, Massalme Elisabeth G, Jappe Uta, Steinmüller-Magin Lars, Schmidt Julia, Hellenbroich Yorck, Hüning Irina, Gillessen-Kaesbach Gabriele, Zillikens Detlef, Hartmann Karin
1Department of Dermatology, Allergology and Venereology, University of Lübeck, Ratzeburger Allee 160, 23538 Lübeck, Germany.
2Division of Clinical and Molecular Allergology, Priority Research Area Asthma and Allergy, Research Center Borstel, Borstel (Sülfeld), Germany.
Clin Transl Allergy. 2019 Feb 14;9:9. doi: 10.1186/s13601-019-0247-x. eCollection 2019.
Hereditary angioedema (HAE) is a life-threatening disease characterized by recurrent episodes of subcutaneous and mucosal swellings and abdominal cramping. Corticosteroids and antihistamines, which are usually beneficial in histamine-induced acquired angioedema, are not effective in HAE. Therefore, diagnosing HAE correctly is crucial for affected patients. We report a family from Northern Germany with six individuals suffering from recurrent swellings, indicating HAE. Laboratory tests and genetic diagnostics of the genes , encoding C1 esterase inhibitor (C1-INH), and encoding coagulation factor XII, were unremarkable. In three affected and one yet unaffected member of the family, we were then able to identify the c.988A > G (also termed c.1100A > G) mutation in the ( gene, which has recently been described in several families with HAE. This mutation leads to a missense mutation with an amino acid exchange p.Lys330Glu in the kringle 3 domain of plasminogen. There was no direct relationship between the earlier described cases with this mutation and the family we report here. In all affected members of the family, the symptoms manifested in adulthood, with swellings of the face, tongue and larynx, including a fatal case of a 19 year-old female individual. The frequency of the attacks was variable, ranging between once per year to once a month. In one individual, we also found decreased serum levels of plasminogen as well as coagulation factor XII. As previously reported in patients with PLG defects, icatibant proved to be very effective in controlling acute attacks, indicating an involvement of bradykinin in the pathogenesis.
遗传性血管性水肿（HAE）是一种危及生命的疾病，其特征为皮下和黏膜反复肿胀以及腹部绞痛。皮质类固醇和抗组胺药通常对组胺诱导的获得性血管性水肿有益，但对HAE无效。因此，正确诊断HAE对患病患者至关重要。我们报告了一个来自德国北部的家族，其中有6人患有反复肿胀，提示为HAE。对编码C1酯酶抑制剂（C1-INH）的基因和编码凝血因子XII的基因进行的实验室检测和基因诊断均无异常。然后，在该家族的3名患病成员和1名未患病成员中，我们在（基因中鉴定出了c.988A > G（也称为c.1100A > G）突变，该突变最近在几个HAE家族中被描述。此突变导致纤溶酶原kringle 3结构域发生错义突变，氨基酸交换为p.Lys330Glu。先前描述的具有此突变的病例与我们在此报告的家族之间没有直接关系。在该家族的所有患病成员中，症状均在成年期出现，表现为面部、舌头和喉部肿胀，其中包括一名19岁女性的致命病例。发作频率各不相同，从每年一次到每月一次不等。在一名个体中，我们还发现其血清纤溶酶原水平以及凝血因子XII水平降低。正如先前在纤溶酶原缺陷患者中所报道的那样，依卡替班在控制急性发作方面被证明非常有效，这表明缓激肽参与了发病机制。
