Breakdown of lysosomal glycogen in cultured fibroblasts from glycogenosis type II patients after uptake of acid alpha-glucosidase.
Fibroblast cultures from patients with different clinical subtypes of glycogenosis type II were compared with respect to residual acid alpha-glucosidase activity and lysosomal glycogen content. Lysosomal glycogen storage was most pronounced in fibroblasts from patients with the rapidly progressive infantile form of the disease, and the most severe enzyme deficiency. In fibroblasts from adult patients with more than 10% of the control activity storage did not occur, and 15% of the total cellular glycogen was found in the lysosomes as in control cells. The strict correlation between residual acid alpha-glucosidase activity and lysosomal glycogen accumulation was further illustrated in two adult Pompe patients with an unusually low enzyme activity. The mild clinical course is unexplained in these particular cases. The enzyme deficiency in all the different mutant cell lines was corrected by the uptake of bovine testis acid alpha-glucosidase from the culture medium. As a result of this, the lysosomal glycogen storage disappeared, and the balance between lysosomal and cytoplasmic glycogen was restored to normal. The implications of this study as a model for enzyme replacement therapy are discussed.
van der Ploeg
A T
AT
Kroos
M
M
van Dongen
J M
JM
Visser
W J
WJ
Bolhuis
P A
PA
Loonen
M C
MC
Reuser
A J
AJ
D002458:Cell Fractionation; D002460:Cell Line; D005347:Fibroblasts / Q000378:metabolism*; D006003:Glycogen / Q000378:metabolism*; D006008:Glycogen Storage Disease / Q000378:metabolism*; D006009:Glycogen Storage Disease Type II / Q000378:metabolism*; D006801:Humans; D008247:Lysosomes / Q000378:metabolism*; D011506:Proteins / Q000378:metabolism; D000520:alpha-Glucosidases / Q000378:metabolism*
D011506:Proteins; D006003:Glycogen; D000520:alpha-Glucosidases