Screening for late-onset Pompe disease in undiagnosed myopathies

Abstract

Background: Pompe disease is caused by a deficiency of acid alpha-glucosidase. Its prevalence varies depending on ethnicity, and is less prevalent in Japan as compared with other countries. Because of the wide spectrum of clinical features in late-onset cases, some patients might be misdiagnosed with another myopathy, thus the actual prevalence in Japan might not be accurately reported. Aim: To clarify the actual prevalence of late-onset Pompe disease, we investigated acid alpha-glucosidase activity in patients with undiagnosed myopathies. Methods: Of 42 patients with undiagnosed myopathies, 41 underwent assessment of acid alpha-glucosidase enzyme activity using dried blood spot analysis. As a second step, reassessment of acid alpha-glucosidase activity was carried out using cultured skin fibroblasts. We also determined acid alpha-glucosidase activity in biopsied muscle tissue obtained from the one other patient, who had previously undergone a muscle biopsy. Finally, gene analysis was carried out to confirm diagnosis. Results: Four patients showed reduced acid alpha-glucosidase activity in dried blood spot findings, of whom one possessed a pseudo-deficiency allele. Furthermore, one patient who showed reduced acid alpha-glucosidase activity in a biopsied muscle specimen was diagnosed with late-onset Pompe disease based on gene analysis. Conclusions: Of the present 42 patients, only one patient was diagnosed with late-onset Pompe disease. The prevalence of Pompe disease in Japan does not seem to be as high as in other countries, though a certain number of patients might exist among those with undiagnosed myopathies. A larger and more systematic survey is necessary to elucidate the actual prevalence of late-onset Pompe disease in Japan.