title: Synthesis and in situ localization of lysosomal alpha-glucosidase in muscle of an unusual variant of glycogen storage disease type II.
abstract: The lysosomal alpha-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 alpha-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 alpha-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 alpha-glucosidase, and as a consequence, an increased residual activity in storage-prone muscle fibers.
authors.affiliation: Department of Clinical Genetics, Erasmus University, Rotterdam, The Netherlands.
authors.forename: R
authors.initials: R
authors.lastname: Willemsen
authors.forename: A T
authors.initials: AT
authors.lastname: van der Ploeg
authors.forename: H F
authors.initials: HF
authors.lastname: Busch
authors.forename: P E
authors.initials: PE
authors.lastname: Zondervan
authors.forename: C J
authors.initials: CJ
authors.lastname: Van Noorden
authors.forename: A J
authors.initials: AJ
authors.lastname: Reuser
mesh_terms: D000135:Acid Phosphatase / Q000032:analysis; D002478:Cells, Cultured; D005260:Female; D005347:Fibroblasts / Q000201:enzymology; D005455:Fluorescent Antibody Technique; D006010:Glycogen Storage Disease Type III / Q000201:enzymology*; D006801:Humans; D007150:Immunohistochemistry; D008247:Lysosomes / Q000201:enzymology*; D016253:Microscopy, Immunoelectron; D008875:Middle Aged; D009132:Muscles / Q000201:enzymology* / Q000648:ultrastructure; D000520:alpha-Glucosidases / Q000032:analysis* / Q000172:deficiency
chemical_list: D000135:Acid Phosphatase; D000520:alpha-Glucosidases