Overview and Etiology

Pompe disease (also known as acid maltase deficiency or glycogen storage disease type II) is a rare genetic lysosomal storage disease with a wide range of clinical phenotypes, presenting in infancy, childhood, or adulthood.1,2 Pompe disease is inherited in an autosomal recessive manner and caused by 2 pathogenic variants in the GAA gene. This leads to an absence or deficiency of the lysosomal enzyme acid α-glucosidase (GAA), essential for the degradation of glycogen. It results in progressive accumulation of lysosomal glycogen that can affect all muscle types.2

Clinical Snapshot

  • Pompe disease is a rare, progressive, often fatal, autosomal recessive lysosomal storage disorder with a wide spectrum of onset, phenotype and severity1
  • Pathogenic variants in the GAA gene cause reduced GAA enzyme activity and the multi-systemic accumulation of glycogen within muscle cells1
  • Pompe disease is characterized by variable onset and presentation and is classified into 2 subtypes: infantile-onset Pompe disease (IOPD) and late-onset Pompe disease (LOPD), affecting the respiratory, musculoskeletal, cardiac, and gastrointestinal systems3
  • IOPD usually presents with symptoms within the first months of life with a rapidly progressive disease course and is usually fatal by 2 years of age. LOPD has a less rapid and more variable disease course and symptoms may begin anywhere from infancy to adulthood. However, the disease is progressive and often leads to respiratory failure and ambulatory complications and the need for mechanical respiratory support and/or ambulatory assistive devices.
  • To diagnose Pompe disease: a GAA-enzyme activity assay resulting in deficient enzyme activity and to confirm, genetic testing resulting in 2 pathogenic GAA alleles4

Pompe disease is inherited in an autosomal recessive manner. With each pregnancy, the chances are5:

  • 1 in 4 (25%) that the child will receive two pathogenic variants and will be affected with Pompe disease
  • 2 in 4 (50%) that the child will be a carrier
  • 1 in 4 (25%) that the child will be unaffected

Although the true frequency cannot be fully determined, it is estimated that the worldwide prevalence of Pompe disease is 1:40,000.2

1. Kishnani PS, Howell RR. J Pediatr. 2004;144(5 Suppl):S35–S43. 2. AANEM. Muscle & Nerve. 2009;40(1):149–160. 3. van der Ploeg AT, Reuser AJ. Lancet. 2008;372(9649):1342–1353.  4. Toscano A, et al. Acta Myol. 2013;32(2):78–81. 5. Taglia A, et al. Acta Myol. 2011;30(3):179–181. 6. Hesselink RP, et al. Biochim Biophys Acta. 2003;1637(2):164–170. 7. Kishnani PS, et al. Genetics in medicine: official journal of the American College of Medical Genetics. 2006;8(5):267–288. 8. Remiche G, et al. Eur Neurol. 2012;68(2):75–78. 9. Kishnani PS, et al. Am J Med Genet A. 2013;161A(10):2431–2443. 10. Secretary's Final Response RE Committee's Recommendation to add Pompe Disease to the RUSP [Internet]. Recommendations to HHS Secretary with Responses. U.S. Department of Health and Human Services. 2015. https://www.hrsa.gov/sites/default/files/hrsa/advisory-committees/heritable-disorders/reports-recommendations/secretary-final-response-pompe.pdf. Accessed October 7, 2019. In.

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