Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.2.1.20 (alpha-glucosidase)
 4,237 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

From January 1985 to January 1990, measurements of acid alpha-D-glucosidase activity in amniocytes or chorionic villus samplings were done for 24 pregnant mothers who were carriers of Pompe's disease. 6 women had two subsequent pregnancies. Amniotic fluid was obtained by transabdominal amniocentesis performed on 10 of them, while chorionic villus samplings were obtained in the other 20. The results showed that 7 (23.3%) cases were homozygotes, 16 (53.4%) cases were heterozygotes, and 7 (23.3%) cases were normal. Pregnancies were terminated in the homozygotic group. Final diagnosis was confirmed by either skin fibroblast culture or clinical course. However, we found that there was overlap in the acid alpha-D-glucosidase activity of amniocytes between homozygotes and heterozygotes due to residual activity of neutral alpha-D-glucosidase. In an attempt to identify heterozygotes for Pompe's disease, we established an enzyme inhibitory assay using monoclonal antibody (mAb) against acid alpha-D-glucosidase. Comparing the differences in alpha-D-glucosidase activity before and after mAb treatment the homozygotes were significantly lower than heterozygotes (P less than 0.001). There was no more overlap in the difference of acid alpha-D-glucosidase activity before and after mAb treatment between heterozygotes and homozygotes in amniocytes. This modified enzyme inhibitory assay should facilitate homozygote detection. Comparing acid alpha-D-glucosidase activity between CVS and amniocytes, the enzyme activity in CVS is about 5 times higher than in amniocytes. There was no overlap in the acid alpha-D-glucosidase activity between homozygotes and heterozygotes. Therefore, CVS is better than amniocentesis in the prenatal diagnosis of Pompe's disease.
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi
PMID:Enzyme inhibitory assay using monoclonal antibody against acid alpha-D-glucosidase in prenatal diagnosis to identify homozygotes of Pompe's disease. 151

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.
Zhonghua Min Guo Xiao Er Ke Yi Xue Hui Za Zhi
PMID:Molecular study on the infantile form of Pompe disease in Chinese in Taiwan. 893 10