The new era of Pompe disease: Advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management


  • Priya S. Kishnani,

    Corresponding author
    • DUMC 103856, 595 Lasalle Street, GSRB 1, 4th Floor, Room 4010, Durham, NC 27710.
    Search for more papers by this author
    • Priya S. Kishnani is Chief of Medical Genetics, Professor of Pediatrics, and a clinician scientist at Duke who is dedicated to the care and treatment of individuals with Pompe disease and other metabolic disorders. In the last two decades her team at Duke has made invaluable contributions in the field of Pompe disease. Dr. Kishnani has been closely involved since the first clinical trial of alglucosidase alfa was started at Duke University Medical Center using the Chinese hamster ovary cell line. The recognition of CRIM negative status and high sustained antibody titers to alglucosidase alfa as negative prognostic factors are some of the contributions made by her team. Development of successful immune modulation strategies to mitigate the immune response to therapeutic proteins and development of new therapies for Pompe disease, Down syndrome, and other glycogen storage diseases are the focus of her Program at Duke.

  • Alexandra A. Beckemeyer,

    Search for more papers by this author
    • Alexandra A. Beckemeyer is an undergraduate research assistant for Priya S. Kishnani at Duke University Medical Center. Ms. Beckmeyer has worked with the Duke Pompe team for the last four years. She has assisted Dr. Kishnani significantly with this supplement, medical book chapters, grant proposals, and other scientific papers.

  • Nancy J. Mendelsohn

    Search for more papers by this author
    • Nancy J. Mendelsohn is the director of Medical Genetics Department at the Children's Hospitals & Clinics of Minnesota. Dr. Mendelsohn has particular interest in helping children with lysosomal storage diseases. Dr. Mendelsohn has collaborated with Dr. Kishnani to provide care for children Pompe disease. Dr. Mendelsohn and Dr. Yoav Messinger at the Children's Hospitals & Clinics of Minnesota have had success in developing immune tolerance for CRIM negative Pompe disease patients.

  • How to cite this article: Kishnani PS, Beckemeyer AA, Mendelsohn NJ. 2012. The new era of Pompe disease: Advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. Am J Med Genet Part C Semin Med Genet 160C:1–7.


Pompe disease is an autosomal recessive neuromuscular disorder marked by progressive muscle weakness due to lysosomal buildup of glycogen. Presentation is described as a spectrum, varying by age of onset, organ involvement, and degree of myopathy. Given the phenotypic variability, Pompe disease is broadly classified into an infantile form and a late onset (juvenile, childhood, adult onset) form. Prior to the advent of enzyme replacement therapy (ERT) with alglucosidase alfa and approval for human use in 2006, the natural history was limited due to death before age 2 years for infantile onset cases and significant morbidity and early mortality for late onset Pompe disease (LOPD). ERT with alglucosidase alfa redefined the once fatal outcome in infantile Pompe, establishing an emergent phenotype. Treatment in late onset patients resulted in improved outcomes, enhancing understanding of the phenotype, presentation, and extent of organ involvement. This Issue of the Seminars seeks to enumerate the recent advancements in the field of Pompe disease, including newborn screening, novel therapeutic targets, new insights in the pathophysiology including role of autophagy, and impacts of long-term disease burden and CNS glycogen accumulation on cognition in infantile survivors. It also addresses immunological challenges and the critical role of immunomodulation in ERT treatment outcome. Other topics discussed include the role of biomarkers in monitoring disease progression and treatment responses, the role of genotype in defining phenotype and treatment response, better insights into the clinical presentations in LOPD and finally the importance of a multidisciplinary approach to care with the role of physical therapy as an example. Many gaps in our scientific understanding of this disease still remain; however, we hope the next decade will bring new knowledge and therapies to the horizon. © 2012 Wiley Periodicals, Inc.