Application of enzyme assay and gene analysis in the prenatal diagnosis for a family with glycogen storage disease type II

Objective To carry out prenatal diagnosis for a glycogen storage disease typeⅡ(GSDⅡ) affected family. Methods The acid-α-glucosidase (GAA) activity was measured in whole leukocytes and cultured amniocytes with 4-methylumbelliferyl-α-D-glucopyranoside as substrate and with acarbose as inhibitor. The coding regions of GAA gene were amplified by polymerase chain reaction and analyzed by direct DNA sequencing. Results The proband and the fetus had low GAA activity (12.3% and 1.1% of the average normal range, respectively). Mutation analysis of the GAA gene revealed a novel nonsense mutation p.W738X and a reported nonsense mutation p.E888X in both the proband and the fetus; the reported pseudodeficiency allele c.[1726G>A;2065G>A] was found in the proband, the mother and the fetus. Conclusion The proband and the fetus were both GSDⅡaffected. A combination of GAA activity analysis and mutation analysis is efficient for the prenatal diagnosis of GSDⅡ. Mutation analysis should be a routine method in the prenatal diagnosis of GSDⅡ in Asian population, where pseudodeficiency allele can cause low GAA activity in normal individuals which is relatively common in Asian. Key words: glycogen storage disease type Ⅱ; acid-alpha-glucosidase; prenatal diagnosis; pseudodeficiency allele