P.212 - Screening for late-onset Pompe disease among high-risk population in Japan

Abstract

Late-onset Pompe disease (LOPD) is a rare, but treatable metabolic myopathy due to acid alpha-glucosidase (GAA) deficiency. LOPD is characterized by progressive muscle weakness and/or respiratory failure, but some LOPD patients without typical signs could be overlooked. To evaluate the utility of Dreid Bood Spots (DBS) in the diagnostic work-up and assess the prevalence of LOPD within a Japanese high-risk population, we prospectively screened for LOPD in a Japanese cohort of undetermined myopathy patients aged one year or older with muscle weakness and/or elevated serum creatine kinase levels. Sixteen neuromuscular center hospitals, members of Muscular Dystrophy Clinical Trial Network (MDCTN), joined the Pompe disease high risk screening study in Japan (PHiRS-J). We tested GAA activity with DBS as first screening method. Patients with reduced GAA activity in DBS were re-analyzed for enzyme activity in lymphocytes, and investigated for GAA gene mutations. Among 113 patients enrolled, two were incompatible with inclution criteria. Nine patients showed reduced GAA activity with DBS. Of these patients, three showed normal GAA enzyme activity in lymphocytes; four were revealed as pseudodeficiency; two with confirmed reduction of GAA activity in lymphocytes were identified to have homozygous or compound heterozygous mutations of the GAA gene. In a Japanese high-risk cohort, we found a prevalence of LOPD around 2%. This study suggests that screening of GAA activity with DBS is useful to diagnose patients with LOPD in a high-risk population.