Demonstration of acid alpha-glucosidase in different types of Pompe disease by use of an immunochemical method.

The nature of mutant acid alpha-glucosidase (AAG) in muscle was studied in 6 patients with Pompe disease, consisting of 2 each of the infantile, childhood and adult types. Anti-human liver AAG rabbit antibody prepared in the present study was confirmed to be monospecific by immunodiffusion, immunotitration and immunohistochemical methods. It was found by the immunodiffusion and enzyme immunoassay methods using this antibody that the mutation produced a normal amount of enzyme protein but the latter was an inactive form, suggesting structural gene mutation in 5 of the 6 cases. In the remaining childhood type case there was no detectable amount of enzyme protein, suggesting that the mutation causes a reduction in the amount of the enzyme protein or synthesis of unstable enzyme protein. Similarly, the enzyme activity of AAG was markedly reduced in all patients, but that of neutral alpha-glucosidase was the least reduced in the adult type, medium in the childhood type, and the most reduced in the infantile type.