Methods of diagnosis of patients with Pompe disease: Data from the Pompe Registry

Pompe disease is a rare, autosomal recessive disorder characterized by deficiency of lysosomal acid alpha-glucosidase and accumulation of lysosomal glycogen in many tissues. The variable clinical manifestations, broad phenotypic spectrum, and overlap of signs and symptoms with other neuromuscular diseases make diagnosis challenging. In the past, the diagnosis of Pompe disease was based on enzyme activity assay in skin fibroblasts or muscle tissue. In 2004, methods for measuring acid alpha-glucosidase activity in blood were published. To compare how diagnostic methods changed over time and whether they differed by geographic region and clinical phenotype, we examined diagnostic methods used for 1059 patients enrolled in the Pompe Registry in three onset categories (Group A: onset of signs/symptoms ≤12months of age with cardiomyopathy; Group B: onset ≤12months without cardiomyopathy and onset >1year to ≤12years; Group C: onset >12years). Enzyme activity-based assays were used more frequently than other diagnostic methods. Measuring acid alpha-glucosidase activity in blood (leukocytes, lymphocytes, or dried-blood spot) increased over time; use of muscle biopsy decreased. The increased use of blood-based assays for diagnosis may result in a more timely diagnosis in patients across the clinical spectrum of Pompe disease. •Enzyme assays, DNA analysis and muscle biopsy were used for Pompe disease diagnosis.•Enzyme activity assays were used most often for diagnosing Pompe Registry patients.•Use of blood-based diagnostic assays increased and use of muscle biopsy decreased.•Increased use of blood-based assays may lead to more timely Pompe disease diagnosis.•Data from the Pompe Registry helps increase understanding of Pompe disease globally.