Purpose: Acid alpha-glucosidase is present in various tissues, including blood cells. Historically, enzyme measurement in cultured fibroblasts, or muscle, has been the gold standard to confirm a diagnosis of Pompe disease, due to the possibility of alternate isoenzyme activity masking disease in white cell assays. Enzyme measurement in an isolated lymphocyte population with acarbose, an inhibitor of neutral alpha-glucosidase, has greatly improved the sensitivity and specificity of the test in blood cells allowing for more rapid laboratory testing for Pompe disease.
Methods: An assay for acid alpha-glucosidase was performed with and without inhibitor in lymphocytes from 14 patients with a clinical suspicion of infantile Pompe disease. Concurrent testing was performed in fibroblasts in an independent laboratory.
Results: Thirteen of 14 patients demonstrated a clear deficiency in lymphocytes with acarbose inhibition. One patient was indeterminate, although below normal activity, suggesting the need for confirmatory testing. Tissue enzyme activity in all was consistent with infantile Pompe disease, and corroborated enzyme activity seen in lymphocytes. There were no false positives for disease, making the positive predictive value of lymphocyte enzyme testing 100%.
Conclusion: Enzyme assay using acarbose as an inhibitor, can be performed in isolated lymphocytes for rapid diagnosis of infantile Pompe disease.