Alpha₁-Antitrypsin Deficiency and Emphysema Caused by Homozygous Inheritance of Non-Expressing Alpha₁-Antitrypsin Genes

Abstract

EMPHYSEMA is a chronic disorder of the lower respiratory tract characterized by enlargement of the air space distal to the terminal bronchioles resulting from destruction of the alveolar walls.1 , 2 In the United States and Europe, approximately 2 percent of cases of emphysema are associated with a hereditary deficiency of α1-antitrypsin,3 4 5 6 a 52-kd glycoprotein produced by hepatocytes and, to a lesser extent, mononuclear phagocytes.7 8 9 10 11 12 13 14 15 16 17 The single gene coding for α1-antitrypsin is contained within a 10-kb segment of DNA composed of five exons on chromosome 14.18–20 The two parental alleles are codominantly expressed, and the α1-antitrypsin . . .