Catz E G, Speir W A
South Med J. 1984 Apr;77(4):479-83.
alpha 1-Antitrypsin, the major serum protease inhibitor, is a glycoprotein synthesized in the liver. Severe deficiency results in protease-antiprotease imbalance, which predisposes to severe emphysema at a young age. Reduced serum levels reflect inadequate release of alpha 1-antitrypsin by the liver, which may be caused by specific defects in biosynthesis. The deficiency is inherited, with multiple codominant alleles at a single autosomal locus. Homozygous individuals, with severely reduced alpha 1-antitrypsin levels, have dyspnea, pulmonary function abnormalities, and respiratory disability from emphysema, usually in the fifth decade of life, with smokers being affected one decade earlier. Heterozygous individuals have intermediate alpha 1-antitrypsin levels and a more benign clinical course. Heterozygous smokers may have mild pulmonary function abnormalities, but these are of uncertain clinical significance. Hepatic involvement with transient neonatal hepatitis and cirrhosis with subsequent liver failure in adulthood represent the major extrapulmonary manifestations, occurring in 10% of homozygous individuals.
α1-抗胰蛋白酶是主要的血清蛋白酶抑制剂，是一种在肝脏中合成的糖蛋白。严重缺乏会导致蛋白酶-抗蛋白酶失衡，这使得个体在年轻时易患严重肺气肿。血清水平降低反映肝脏释放α1-抗胰蛋白酶不足，这可能由生物合成中的特定缺陷引起。这种缺乏是遗传性的，在单个常染色体位点上有多个共显性等位基因。纯合个体的α1-抗胰蛋白酶水平严重降低，通常在生命的第五个十年出现呼吸困难、肺功能异常以及因肺气肿导致的呼吸功能障碍，吸烟者发病时间提前十年。杂合个体的α1-抗胰蛋白酶水平处于中等，临床病程较为良性。杂合吸烟者可能有轻度肺功能异常，但这些异常的临床意义尚不确定。肝脏受累表现为短暂性新生儿肝炎以及成年后出现肝硬化并随后发生肝衰竭，这是主要的肺外表现，见于10%的纯合个体。
