Department of Medicine, Royal College of Surgeons in Ireland Education and Research Centre, Beaumont Hospital, Dublin 9, Ireland.
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, UK.
Nat Rev Dis Primers. 2016 Jul 28;2:16051. doi: 10.1038/nrdp.2016.51.
α1-Antitrypsin deficiency (A1ATD) is an inherited disorder caused by mutations in SERPINA1, leading to liver and lung disease. It is not a rare disorder but frequently goes underdiagnosed or misdiagnosed as asthma, chronic obstructive pulmonary disease (COPD) or cryptogenic liver disease. The most frequent disease-associated mutations include the S allele and the Z allele of SERPINA1, which lead to the accumulation of misfolded α1-antitrypsin in hepatocytes, endoplasmic reticulum stress, low circulating levels of α1-antitrypsin and liver disease. Currently, there is no cure for severe liver disease and the only management option is liver transplantation when liver failure is life-threatening. A1ATD-associated lung disease predominately occurs in adults and is caused principally by inadequate protease inhibition. Treatment of A1ATD-associated lung disease includes standard therapies that are also used for the treatment of COPD, in addition to the use of augmentation therapy (that is, infusions of human plasma-derived, purified α1-antitrypsin). New therapies that target the misfolded α1-antitrypsin or attempt to correct the underlying genetic mutation are currently under development.
α1-抗胰蛋白酶缺乏症（A1ATD）是一种由 SERPINA1 基因突变引起的遗传性疾病，可导致肝脏和肺部疾病。它并不罕见，但经常被误诊或漏诊为哮喘、慢性阻塞性肺疾病（COPD）或不明原因的肝脏疾病。最常见的与疾病相关的突变包括 SERPINA1 的 S 等位基因和 Z 等位基因，这导致错误折叠的 α1-抗胰蛋白酶在肝细胞中积累、内质网应激、α1-抗胰蛋白酶的循环水平降低和肝脏疾病。目前，严重的肝脏疾病尚无治愈方法，当肝功能衰竭危及生命时，唯一的治疗选择是肝移植。A1ATD 相关的肺部疾病主要发生在成年人，主要是由于蛋白酶抑制不足引起的。A1ATD 相关肺部疾病的治疗包括标准治疗，这些治疗也用于 COPD 的治疗，此外还使用增敏治疗（即输注人血浆源性、纯化的 α1-抗胰蛋白酶）。目前正在开发针对错误折叠的 α1-抗胰蛋白酶或试图纠正潜在遗传突变的新疗法。
