Alpha1-Antitrypsin Deficiency Emphysema

With the exception of cystic fibrosis, inborn errors of metabolism have hardly ever entered into etiologic considerations of bronchopulmonary disease. Thus, when in 1963 Laurell and Eriksson¹ reported an association between emphysema and alpha₁-antitrypsin deficiency in three out of five patients in whom they discovered this dysproteinemia (in the course of a routine analysis of 1,500 sera), they aroused much interest. The interest deepened when a subsequent study² of the familial pedigree of one of these patients disclosed three levels of alpha₁-antitrypsin concentration among its members: normal, 60%, and less than 10% of normal. The last two levels strongly suggested a heterozygous and a homozygous state of a recessive autosomal mode of inheritance. The majority, but not all of homozygotes had emphysema; none of the heterozygotes had the disease.

Pursuing the investigation further, Eriksson³ studied 14 families with one or more cases of