Alpha-1 Antitrypsin Deficiency

Abstract

Alpha-1 antitrypsin (a1-AT) deficiency is the most common genetic cause of liver disease. The inheritance of a1-AT deficiency follows an autosomal recessive pattern. It affects 1‐1,600 to 2,000 live births in North Americans and the European population, respectively, but is less common in other ethnic groups. a1-AT is a glycoprotein synthesized primarily in the liver and to a lesser extent by other tissues, including macrophages, renal tubular, and small intestinal epithelial cells. It functions as a serine protease inhibitor with its main target being leukocyte elastase. The most common form of the disease, PiZZ, results in the production of abnormal a1-AT. Only a small proportion of patients with a1-AT deficiency will develop clinically significant liver disease but it is the main cause of emphysema in adults. In addition to lung and liver disease, several disorders have beenreported inassociationwitha1-ATdeficiency including systemic vasculitis, interstitial fibrosis in patients with rheumatoid arthritis, relapsing panniculitis, multiple sclerosis, peripheral neuropathy, and intracranial aneurysms.