Glycogen-storage disease type II, Pompe disease, is caused by the deficiency of 
acid alpha-D-glucosidase in lysosome. Previously we found that acid 
alpha-D-glucosidase did exist in the skin fibroblasts and there was also no 
difference of mRNA in quantity and size of Chinese infantile type Pompe disease 
patients in Taiwan. However, functional assay of the acid alpha-D-glucosidase of 
these patients showed its enzyme function to be defective. In the present study, 
first we identified a substitution site in four Chinese infantile patients with 
Pompe disease which is a cytidine to adenosine (C1935-->A) transversion at 5' 
end of exon 14 causing substitution of glutamic acid for aspartic acid at 
position 645 of the acid alpha-D-glucosidase. This substitution was introduced 
in wild-type cDNA and expressed in COS-1 cells. The Asp-645-->Glu substitution 
resulted in significant reduction of acid alpha-D-glucosidase activity. Second, 
according to the screening data in 25 Chinese Pompe disease patients using 
digestion of RT-PCR amplified specific fragment with Aat II, the restriction 
fragment length analysis showed that patients presented the 861 bp band and the 
normal individuals presented the 728 bp and 133 bp polymorphic bands. We found 
that the frequency of mutant allele is 0.8 in infantile patients with Chinese 
Pompe disease and 0 in normal individuals. These results therefore indicate that 
Asp-645-->Glu mutation results in infantile form of Pompe disease as the major 
cause in Chinese patients in Taiwan.