SYNTHESIS AND IN-SITU LOCALIZATION OF LYSOSOMAL ALPHA-GLUCOSIDASE IN MUSCLE OF AN UNUSUAL VARIANT OF GLYCOGEN-STORAGE-DISEASE TYPE-II

The lysosomal alpha-glucosidase activity is reduced to 10% to 25% of t he average control value in most late-onset cases of glycogen storage disease type II (GSDII). Some adult patients, however, have been ident ified with an exceptionally low (<5%) residual enzyme activity. We hav e investigated one such unusual variant. The rate of alpha-glucosidase synthesis appeared normal but the residual enzyme activity was only a pproximately 3% in cultured fibroblasts, cultured muscle cells, and mu scle tissue of the patient. It appeared that fully matured enzyme mole cules were more abundantly present in muscle tissue than in cultured c ells. The acid phosphatase activity of affected muscle fibers was enha nced due to an increased number of lysosomes. Lysosomes were particula rly abundant in vacuolated areas and they contained, as judged by immu noelectron microscopy, even more alpha-glucosidase molecules than usua l. An excessive amount of enzyme molecules were also observed in the e ndoplasmic 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 an d onset of cellular injury. We hypothesize that the onset of gross pat hologic abnormalities is delayed in this particular case of adult GSDI I by an increased synthesis of lysosomal alpha-glucosidase, and as a c onsequence, an increased residual activity in storage-prone muscle fib ers.