Determination of acid alpha-glucosidase protein: Evaluation as a screeningmarker for pompe disease and other lysosomal storage disorders

Background: In recent years, there have been significant advances in the de velopment of enzyme replacement and other therapies for lysosomal storage d isorders (LSDs). Early diagnosis, before the onset of irreversible patholog y, has been demonstrated to be critical for maximum efficacy of current and proposed therapies. In the absence of a family history, the presymptomatic detection of these disorders ideally can be achieved through a newborn scr eening program. One approach to the development of such a program is the id entification of suitable screening markers. In this study, the acid alpha-g lucosidase protein was evaluated as a marker protein for Pompe disease and potentially for other LSDs. Methods: Two sensitive immunoquantification assays for the measurement of t otal (precursor and mature) and mature forms of acid alpha-glucosidase prot ein were used to determine the concentrations in plasma and dried blood spo ts from control and LSD-affected individuals. Results: In the majority of LSDs, no significant increases above control va lues were observed. However, individuals with Pompe disease showed a marked decrease in acid alpha-glucosidase protein in both plasma and whole blood compared with unaffected controls. For plasma samples, this assay gave a se nsitivity of 95% with a specificity of 100%. For blood spot samples, the se nsitivity was 82% with a specificity of 100%. Conclusions: This study demonstrates that it is possible to screen for Pomp e disease by screening the concentration of total acid Lu-glucosidase in pl asma or dried blood spots. (C) 2000 American Association for Clinical Chemi stry.