title: Methods of diagnosis of patients with Pompe disease: Data from the Pompe Registry.
abstract: 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 ≤ 12 months of age with cardiomyopathy; Group B: onset ≤ 12 months without cardiomyopathy and onset >1 year to ≤ 12 years; Group C: onset >12 years). 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.
authors.affiliation: Division of Medical Genetics, Department of Pediatrics, Duke University Medical Center, Box 103856 DUMC, 4th Floor GSRBI, 595 LaSalle Street, Durham, NC 22710, USA. Electronic address: kishn001@mc.duke.edu.
authors.forename: Priya S
authors.initials: PS
authors.lastname: Kishnani
authors.affiliation: Division of Child Neurology, Department of Pediatrics, Austral University Hospital, Juan Domingo Peron 1500, Pilar (B16641NZ), Buenos Aires, Argentina.
authors.forename: Hernán M
authors.initials: HM
authors.lastname: Amartino
authors.affiliation: Neuromuscular Centre, Sahlgrenska University Hospital, S-413 45 Gothenburg, Sweden.
authors.forename: Christopher
authors.initials: C
authors.lastname: Lindberg
authors.affiliation: Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Timothy M
authors.initials: TM
authors.lastname: Miller
authors.affiliation: Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Amanda
authors.initials: A
authors.lastname: Wilson
authors.affiliation: Genzyme, a Sanofi company, 500 Kendall Street, Cambridge, MA 02142, USA.
authors.forename: Joan
authors.initials: J
authors.lastname: Keutzer
mesh_terms: D000293:Adolescent; D001706:Biopsy; D002648:Child; D002675:Child, Preschool; D057075:Enzyme Assays / Q000379:methods; D005260:Female; D005820:Genetic Testing / Q000379:methods; D006009:Glycogen Storage Disease Type II / Q000175:diagnosis*; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008297:Male; D018482:Muscle, Skeletal / Q000473:pathology; D012042:Registries
keywords: Diagnosis; Dried blood spots; GAA enzyme assays; Lysosomal storage disorder; Pompe disease; Registry