ABSTRACT
The laboratory diagnosis of alpha 1-antitrypsin (alAT) deficiency began in 1963 when C. B. Laurell and S. Eriksson, using a combination of paper electrophoresis, agar-gel electrophoresis, and immunoelectrophoresis, determined the association of familial emphysema with the absence of the alpha 1-globulin band (1). The use of starch-gel electrophoresis to evaluate the electrophoretic polymorphism in the prealbumin region led to the identification of the multiallelic Pi (protease inhibi tor) system. Subsequently, these techniques were replaced by isoelectric focusing (IEF) of serum in polyacrylamide gels, which provides better a 1 AT band resolu tion (2). The development of immobilized pH gradients (IPG) in the early 1980s further increased the resolution between minor pH differences to 1/100 of a pH unit, making it possible to separate variants that have only minor pH differences (3). The cloning and DNA sequencing of the a l AT cDNA, and later the genomic segment, provided the DNA-sequence information necessary to identify prac tically the genotypes of individuals (4,5).
