Bull World Health Organ. 1997;75(5):397-415.
alpha 1-Antitrypsin (AAT) deficiency, also known as alpha 1-antiprotease inhibitor deficiency, is a disease caused by genetically determined AAT deficiency. It occurs as a result of inheritance of two protease inhibitor (PI) deficiency alleles from the AAT gene locus (designated PI) on chromosomal segment 14q32.1. The most common deficiency allele is PI*Z and a large majority of individuals with severe AAT deficiency are PI type ZZ. The disease occurs predominantly in white persons of European origin and its frequency in Europe and North America is comparable to that of cystic fibrosis (1 in 2000 to 1 in 7000.) Persons with AAT deficiency may have no clinical manifestations. Chronic obstructive pulmonary disease (COPD) with a high frequency of panacinar emphysema is the most prevalent clinical disorder associated with AAT deficiency and the most frequent cause of disability and death. Tobacco smoking is the major risk factor for developing COPD, which generally begins by the third decade of life, much earlier than "usual" COPD that occurs in AAT-replete individuals. Liver disease, the second most frequent clinical manifestation of AAT deficiency, typically presents as cholestasis in infancy but is usually not severe and generally remits by adolescence. Chronic liver disease develops infrequently, although AAT deficiency is the commonest cause of chronic liver disease in childhood. Cirrhosis and carcinoma of the liver affect at least 25% of AAT-deficient adults over the age of 50 years. AAT deficiency appears to be widely underdiagnosed and based on predicted gene frequencies even in the most intensely studied populations, only a small proportion of those predicted to have AAT deficiency have been diagnosed. Human AAT is available in limited quantity for augmentation therapy. This Memorandum summarizes the discussions and recommendations made by participants at a WHO meeting held in Geneva on 18-20 March 1996 to review existing knowledge about this highly prevalent genetic disorder, develop a strategy for enhancing awareness of it among health-care-givers and the general public, and explore new case-finding and disease-prevention strategies.
α1-抗胰蛋白酶（AAT）缺乏症，也称为α1-抗蛋白酶抑制剂缺乏症，是一种由基因决定的AAT缺乏引起的疾病。它是由于从染色体14q32.1上的AAT基因座（称为PI）遗传了两个蛋白酶抑制剂（PI）缺乏等位基因而发生的。最常见的缺乏等位基因是PI*Z，绝大多数严重AAT缺乏的个体是PI ZZ型。该疾病主要发生在欧洲血统的白人中，其在欧洲和北美的发病率与囊性纤维化相当（2000分之一至7000分之一）。AAT缺乏症患者可能没有临床表现。伴有全腺泡型肺气肿高发生率的慢性阻塞性肺疾病（COPD）是与AAT缺乏相关的最常见临床病症，也是致残和死亡的最常见原因。吸烟是患COPD的主要危险因素，COPD通常在生命的第三个十年开始，比AAT充足个体中发生的“普通”COPD要早得多。肝脏疾病是AAT缺乏症的第二常见临床表现，通常在婴儿期表现为胆汁淤积，但通常不严重，一般在青春期缓解。慢性肝病很少发生，尽管AAT缺乏是儿童慢性肝病的最常见原因。肝硬化和肝癌影响至少25%的50岁以上AAT缺乏的成年人。即使在研究最深入的人群中，基于预测的基因频率，AAT缺乏症似乎也广泛存在诊断不足的情况，只有一小部分预计患有AAT缺乏症的人被诊断出来。用于增强治疗的人AAT数量有限。本备忘录总结了1996年3月18日至20日在日内瓦举行的一次世卫组织会议上与会者的讨论和建议，该会议旨在审查关于这种高度流行的遗传疾病的现有知识，制定提高医护人员和公众对其认识的战略，并探索新的病例发现和疾病预防战略。
