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Determination of Acid -Glucosidase Protein: Evaluation as a Screening Marker for Pompe Disease and Other Lysosomal Storage Disorders

¹ Lysosomal Diseases Research Unit and
² State Screening Services, Department of Chemical Pathology, Women’s and Children’s Hospital, 72 King William Rd., North Adelaide, South Australia 5006, Australia.

³ Department of Clinical Genetics, Erasmus University, PO Box 1738, 3000 DR Rotterdam, The Netherlands.
^a Author for correspondence. Fax 61-8-8204-7100; e-mail pmeikle{at}medicine.adelaide.edu.au

Background: In recent years, there have been significant advances in the development of enzyme replacement and other therapies for lysosomal storage disorders (LSDs). Early diagnosis, before the onset of irreversible pathology, 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 screening program. One approach to the development of such a program is the identification of suitable screening markers. In this study, the acid -glucosidase protein was evaluated as a marker protein for Pompe disease and potentially for other LSDs.

Methods: Two sensitive immunoquantification assays for the measurement of total (precursor and mature) and mature forms of acid -glucosidase protein were used to determine the concentrations in plasma and dried blood spots from control and LSD-affected individuals.

Results: In the majority of LSDs, no significant increases above control values were observed. However, individuals with Pompe disease showed a marked decrease in acid -glucosidase protein in both plasma and whole blood compared with unaffected controls. For plasma samples, this assay gave a sensitivity of 95% with a specificity of 100%. For blood spot samples, the sensitivity was 82% with a specificity of 100%.

Conclusions: This study demonstrates that it is possible to screen for Pompe disease by screening the concentration of total acid -glucosidase in plasma or dried blood spots.

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