Glycogen storage disease type II: enzymatic screening in dried blood spots on filter paper.

BACKGROUND: Glycogen storage disease II is characterized by a deficiency of the lysosomal enzyme acid alpha-glucosidase. Currently, glycogen storage disease II is diagnosed by demonstrating the virtual absence or a marked reduction of acid alpha-glucosidase activity in muscle biopsies, cultured fibroblasts, or purified lymphocytes. Early diagnosis and treatment of glycogen storage disease II are considered to be critical for maximum efficacy of the enzyme replacement therapies that are in development. However, these existing diagnostic methods are not suited for newborn screening. We developed an assay useful for newborn screening for glycogen storage disease II. METHODS: A series of three enzyme assays to measure the alpha-glucosidase activities in dried blood spots on filter paper was developed. The measurement of acid alpha-glucosidase activity with minimal interference by other alpha-glucosidases was accomplished using maltose as an inhibitor. The method was used on samples from glycogen storage disease II patients, obligate heterozygotes, and healthy controls. RESULTS: Glycogen storage disease II patients were distinguished from carriers and healthy controls using the series of enzyme assays. CONCLUSIONS: We developed a simple and noninvasive screening method for glycogen storage disease II. The method could be incorporated into newborn screening.