REDUCED CATALYTIC ACTIVITY FOR GLYCOGEN OF ACID a-GLUCOSIDASE TYPE 2 FIBROBLASTS

The lysosomal enzyme acid a-glucosidase (a-G) catalyzes the clevage of glucose from glycogen. Three phenotypes of a-G, 1,2 and 2-1, determined by two alleles at an autosomal locus, have been identified in normal subjects (Ann. Hum. Genet.,38:391, 1975). Using maltose as substrate the a-G activity in cultured fibroblasts (FB) homozygous for a-G type 1 (common allele) was 233 ± 95.1 μg glucose/mg protein/hr, whereas the activity in a FB strain homozygous for a-G typw 2 was 81.5 (35% of normal). Using glycogen as substrate the activity in the normal fibroblasts was 124.8 (53.4% of that obtained with maltose), whereas in the a-G 2 FB it was 8.4 (10.3%). The specific activity, therefore, in the a-G 2 FB when glycogen was the substrate was only 6.7% of that measured in the a-G 1 FB. By using the same amount of enzyme activity (measured with maltose) the size of the precipitin arcs obtained by rocket immunoelectrophoresis was the same in a-G types 1 and 2 FB. These findings indicate that FB homozygous for a-G 2 are deficient toward glycogen because of a functionally abnormal enzyme. Since the residual activity in the FB of patients with the adult form of a-G deficiency may be up to 22% of normal, it is possible that homozygotes for a-G 2 may develop a muscular dystrophy-like disease later in life.