Synthesis and In Situ Localization of Lysosomal α-Glucosidase in Muscle of an Unusual Variant of Glycogen Storage Disease Type II

Abstract

The lysosomal α-glucosidase activity is reduced to 10% to 25% of the average control value in most late-onset cases of glycogen storage disease type II (GSDII). Some adult patients, however, have been identified with an exceptionally low (<5%) residual enzyme activity. We have investigated one such unusual variant. The rate of α-glucosidase synthesis appeared normal but the residual enzyme activity was only approximately 3% in cultured fibroblasts, cultured muscle cells, and muscle tissue of the patient. It appeared that fully matured enzyme molecules were more abundantly present in muscle tissue than in cultured cells. The acid phosphatase activity of affected muscle fibers was enhanced due to an increased number of lysosomes. Lysosomes were particularly abundant in vacuolated areas and they contained, as judged by immunoelectron microscopy, even more α-glucosidase molecules than usual. An excessive amount of enzyme molecules were also observed in the endoplasmic reticulum, the site of lysosomal enzyme synthesis, and the cisternae were dilated. These observations suggest that the lysosomal system is stimulated in response to intralysosomal glycogen storage and onset of cellular injury. We hypothesize that the onset of gross pathologic abnormalities is delayed in this particular case of adult GSDII by an increased synthesis of lysosomal α-glucosidase, and as a consequence, an increased residual activity in storage-prone muscle fibers.

Key Words:

• α-glucosidase
• glycogenosis
• lysosome
• maltase
• Pompe