Clinical Features and Natural History of Severe α1-Antitrypsin Deficiency: Roger S. Mitchell Lecture

Abstract

Since its first description by Laurell and Eriksson1 in 1963, α1-antitrypsin (α1-AT) deficiency has been studied extensively, with substantial strides made in understanding the cellular and molecular biology of this disorder. The α1-AT gene has been located on the long arm of chromosome 14 and the gene has been sequenced and cloned.2 The complete primary structure of the normal α1-AT molecule has been characterized, and the mechanism of impaired hepatic secretion of the most common severe deficiency variant, the Z-type protein, has been characterized as “loop-sheet polymerization.”3 In the context of this extensive basic understanding, it remains a paradox that current cellular and molecular understanding of α1-AT deficiency greatly outstrips current knowledge about clinical aspects of this disease.