Fibroblasts from patients with the adult, juvenile, and infantile form of
glycogenosis type II (
Pompe disease) were cultured under standardized conditions, and the activity of
acid alpha-glucosidase (E.C.3.2.1.20) towards
glycogen,
maltose, and
4-methylumbelliferyl-alpha-D-glucopyranoside was measured.
Glycogen levels in muscle biopsies and in cultured fibroblasts from patients were determined. Residual
enzyme activities varying from 7%-22% were detected in fibroblasts from patients with the adult form but not from patients with the infantile form of
glycogenosis II. An inverse correlation was found between the severity of the clinical manifestation and the degree of residual
enzyme activity in the fibroblasts. The kinetic and electrophoretic properties of
acid alpha-glucosidase in fibroblasts from the adult patients and from control individuals were similar. Immunological studies suggested that the decrease of
acid alpha-glucosidase activity is caused by a mutation that affects the production or degradation of the
enzyme rather than its catalytic activity. Complementation studies were carried out by fusing fibroblasts from patients with the adult, juvenile, and infantile form of
glycogenosis II, but neither conventional assays on multikaryons nor
enzyme assays on single binuclear heterokaryons gave any evidence for genetic heterogeneity among these forms.