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

Abstract

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.

Authors+Show Affiliations

DUMC, Durham, NC 27710, USA. kishn001@mc.duke.eduNo affiliation info availableNo affiliation info available

Pub Type(s)

Introductory Journal Article

Language

eng

PubMed ID

22253049

Citation

Kishnani, Priya S., et al. "The New Era of Pompe Disease: Advances in the Detection, Understanding of the Phenotypic Spectrum, Pathophysiology, and Management." American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, vol. 160C, no. 1, 2012, pp. 1-7.
Kishnani PS, Beckemeyer AA, Mendelsohn NJ. The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. Am J Med Genet C Semin Med Genet. 2012;160C(1):1-7.
Kishnani, P. S., Beckemeyer, A. A., & Mendelsohn, N. J. (2012). The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. American Journal of Medical Genetics. Part C, Seminars in Medical Genetics, 160C(1), pp. 1-7. doi:10.1002/ajmg.c.31324.
Kishnani PS, Beckemeyer AA, Mendelsohn NJ. The New Era of Pompe Disease: Advances in the Detection, Understanding of the Phenotypic Spectrum, Pathophysiology, and Management. Am J Med Genet C Semin Med Genet. 2012 Feb 15;160C(1):1-7. PubMed PMID: 22253049.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The new era of Pompe disease: advances in the detection, understanding of the phenotypic spectrum, pathophysiology, and management. AU - Kishnani,Priya S, AU - Beckemeyer,Alexandra A, AU - Mendelsohn,Nancy J, Y1 - 2012/01/17/ PY - 2012/1/19/entrez PY - 2012/1/19/pubmed PY - 2012/7/25/medline SP - 1 EP - 7 JF - American journal of medical genetics. Part C, Seminars in medical genetics JO - Am J Med Genet C Semin Med Genet VL - 160C IS - 1 N2 - 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. SN - 1552-4876 UR - https://www.unboundmedicine.com/medline/citation/22253049/The_new_era_of_Pompe_disease:_advances_in_the_detection_understanding_of_the_phenotypic_spectrum_pathophysiology_and_management_ L2 - https://doi.org/10.1002/ajmg.c.31324 DB - PRIME DP - Unbound Medicine ER -