Skip to main content

Advertisement

SpringerLink
Log in

Acid alpha-glucosidase deficiency (Pompe disease)

  • Published:
Current Neurology and Neuroscience Reports Aims and scope Submit manuscript

Abstract

The development and recent approval of recombinant acid alpha-glucosidase for enzyme replacement therapy have been major milestones in Pompe disease research. Acid alpha-glucosidase is the enzyme responsible for degradation of glycogen polymers to glucose in the acidic milieu of the lysosomes. Cardiac and skeletal muscles are the two major tissues affected by the accumulation of glycogen within the lysosomes. Both cardiomyopathy and skeletal muscle myopathy are observed in patients with complete enzyme deficiency; this form of the disease is fatal within the first year of life. Skeletal muscle myopathy eventually leading to respiratory insufficiency is the predominant manifestation of partial enzyme deficiency. The recombinant enzyme alglucosidase alfa is the first drug ever approved for this devastating disorder. This review discusses the benefits and the shortcomings of the new therapy.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References and Recommended Reading

  1. Pompe JC: Over idiopatische hypertrophie van het hart. Ned Tijdschr Geneeskd 1932, 76:304.

    Google Scholar 

  2. Hers HG: Alpha-glucosidase deficiency in generalize glycogen storage disease (Pompe’s disease). Biochem J 1963, 86:11.

    PubMed  CAS  Google Scholar 

  3. Sly WS: Enzyme replacement therapy for lysosomal storage disorders: successful transition from concept to clinical practice. Mo Med 2004, 101:100–104.

    PubMed  Google Scholar 

  4. Acid maltase deficiency. In Myology. Edited by Engel AG, Franzini-Armstrong C. New York: McGraw-Hill; 2003:1559–1586.

    Google Scholar 

  5. Kishnani PS, Steiner RD, Bali D, et al.: Pompe disease diagnosis and management guideline. Genet Med 2006, 8:267–288.

    PubMed  Google Scholar 

  6. Slonim AE, Bulone L, Ritz S, et al.: Identification of two subtypes of infantile acid maltase deficiency. J Pediatr 2000, 137:283–285.

    Article  PubMed  CAS  Google Scholar 

  7. Kishnani PS, Howell RR: Pompe disease in infants and children. J Pediatr 2004, 144:S35–S43.

    Article  PubMed  CAS  Google Scholar 

  8. Martiniuk F, Chen A, Mack A, et al.: Carrier frequency for glycogen storage disease type II in New York and estimates of affected individuals born with the disease. Am J Med Genet 1998, 79:69–72.

    Article  PubMed  CAS  Google Scholar 

  9. Van den Hout HM, Hop W, van Diggelen OP, et al.: The natural course of infantile Pompe’s disease: 20 original cases compared with 133 cases from the literature. Pediatrics 2003, 112:332–340.

    Article  PubMed  Google Scholar 

  10. Kishnani PS, Hwu WL, Mandel H, et al.: A retrospective, multinational, multicenter study on the natural history of infantile-onset Pompe disease. J Pediatr 2006, 148:671–676.

    Article  PubMed  Google Scholar 

  11. Hagemans ML, Winkel LP, Van Doorn PA, et al.: Clinical manifestation and natural course of late-onset Pompe’s disease in 54 Dutch patients. Brain 2005, 128:671–677.

    Article  PubMed  CAS  Google Scholar 

  12. Winkel LP, Hagemans ML, Van Doorn PA, et al.: The natural course of non-classic Pompe’s disease; a review of 225 published cases. J Neurol 2005, 252:875–884.

    Article  PubMed  Google Scholar 

  13. Kornfeld S: Structure and function of the mannose 6-phosphate/insulinlike growth factor II receptors. Annu Rev Biochem 1992, 61:307–330.

    Article  PubMed  CAS  Google Scholar 

  14. Ghosh P, Dahms NM, Kornfeld S: Mannose 6-phosphate receptors: new twists in the tale. Nat Rev Mol Cell Biol 2003, 4:202–212.

    Article  PubMed  CAS  Google Scholar 

  15. Wisselaar HA, Kroos MA, Hermans MM, et al.: Structural and functional changes of lysosomal acid alpha-glucosidase during intracellular transport and maturation. J Biol Chem 1993, 268:2223–2231.

    PubMed  CAS  Google Scholar 

  16. Moreland RJ, Jin X, Zhang XK, et al.: Lysosomal acid alpha-glucosidase consists of four different peptides processed from a single chain precursor. J Biol Chem 2005, 280:6780–6791.

    Article  PubMed  CAS  Google Scholar 

  17. Van den Hout H., Reuser AJ, Vulto AG, et al.: Recombinant human alpha-glucosidase from rabbit milk in Pompe patients. Lancet 2000, 356:397–398.

    Article  PubMed  Google Scholar 

  18. Van den Hout JM, Kamphoven JH, Winkel LP, et al.: Long-term intravenous treatment of Pompe disease with recombinant human alpha-glucosidase from milk. Pediatrics 2004, 113:e448–e457.

    Article  PubMed  Google Scholar 

  19. Klinge L, Straub V, Neudorf U, Voit T: Enzyme replacement therapy in classical infantile pompe disease: results of a ten-month follow-up study. Neuropediatrics 2005, 36:6–11.

    Article  PubMed  CAS  Google Scholar 

  20. Winkel LP, Van den Hout JM, Kamphoven JH, et al.: Enzyme replacement therapy in late-onset Pompe’s disease: a three-year follow-up. Ann Neurol 2004, 55:495–502.

    Article  PubMed  CAS  Google Scholar 

  21. Amalfitano A, Bengur AR, Morse RP, et al.: Recombinant human acid alpha-glucosidase enzyme therapy for infantile glycogen storage disease type II: results of a phase I/II clinical trial. Genet Med 2001, 3:132–138.

    PubMed  CAS  Google Scholar 

  22. Kishnani P, Nicolino M, Voit T, et al.: Chinese hamster ovary cell-derived recombinant human acid alpha-glucosidase in infantile-onset Pompe disease. J Pediatr 2006, 149:89–97.

    Article  PubMed  CAS  Google Scholar 

  23. Ansong AK, Li JS, Nozik-Grayck E, et al.: Electrocardiographic response to enzyme replacement therapy for Pompe disease. Genet Med 2006, 8:297–301.

    PubMed  CAS  Google Scholar 

  24. Cook AL, Kishnani PS, Carboni MP, et al.: Ambulatory electrocardiogram analysis in infants treated with recombinant human acid alpha-glucosidase enzyme replacement therapy for Pompe disease. Genet Med 2006, 8:313–317.

    PubMed  CAS  Google Scholar 

  25. Winkel LP, Kamphoven JH, Van Den Hout HJ, et al.: Morphological changes in muscle tissue of patients with infantile Pompe’s disease receiving enzyme replacement therapy. Muscle Nerve 2003, 27:743–751.

    Article  PubMed  CAS  Google Scholar 

  26. Thurberg BL, Lynch Maloney C, Vaccaro C, et al.: Characterization of pre-and post-treatment pathology after enzyme replacement therapy for pompe disease. Lab Invest 2006, In press.

  27. Griffin JL: Infantile acid maltase deficiency. I. Muscle fiber destruction after lysosomal rupture. Virchows Arch B Cell Pathol Incl Mol Pathol 1984, 45:23–36.

    PubMed  CAS  Google Scholar 

  28. Griffin JL: Infantile acid maltase deficiency. II. Muscle fiber hypertrophy and the ultrastructure of end-stage fibers. Virchows Arch B Cell Pathol Incl Mol Pathol 1984, 45:37–50.

    Article  PubMed  CAS  Google Scholar 

  29. Engel AG: Acid maltase deficiency in adults: studies in four cases of a syndrome which may mimic muscular dystrophy or other myopathies. Brain 1970, 93:599–616.

    Article  PubMed  CAS  Google Scholar 

  30. Vita G, Migliorato A, Toscano A, et al.: Immunocytochemistry of muscle cytoskeletal proteins in acid maltase deficiency. Muscle Nerve 1994, 17:655–661.

    Article  PubMed  CAS  Google Scholar 

  31. Angelini C, Cenacchi G, Nascimbeni AC, Fulizio L: Morphological changes in late onset acid Maltase deficient patients with splicing gene mutation. Acta Myol 2003, 22:90–96.

    PubMed  CAS  Google Scholar 

  32. Sharma MC, Schultze C, von Moers A, et al.: Delayed or late-onset type II glycogenosis with globular inclusions. Acta Neuropathol (Berl) 2005, 110:151–157.

    Article  Google Scholar 

  33. Yorimitsu T, Klionsky DJ: Autophagy: molecular machinery for self-eating. Cell Death Differ 2005, 12(Suppl 2):1542–1552.

    Article  PubMed  CAS  Google Scholar 

  34. Orth M, Mundegar RR: Effect of acid maltase deficiency on the endosomal/lysosomal system and glucose transporter 4. Neuromuscul Disord 2003, 13:49–54.

    Article  PubMed  CAS  Google Scholar 

  35. Raben N, Danon M, Gilbert AL, et al.: Enzyme replacement therapy in the mouse model of Pompe disease. Mol Genet Metab 2003, 80:159–169.

    Article  PubMed  CAS  Google Scholar 

  36. Raben N, Fukuda T, Gilbert AL, et al.: Replacing acid alpha-glucosidase in Pompe disease: recombinant and transgenic enzymes are equipotent, but neither completely clears glycogen from type II muscle fibers. Mol Ther 2005, 11:48–56.

    Article  PubMed  CAS  Google Scholar 

  37. Fukuda T, Ewan L, Bauer M, et al.: Dysfunction of endocytic and autophagic pathways in a lysosomal storage disease. Ann Neurol 2006, 9:700–708.

    Article  CAS  Google Scholar 

  38. Fukuda T, Roberts A, Ahearn M, et al.: Autophagy and lysosomes in Pompe disease. Autophagy 2006, 5:2.

    Google Scholar 

  39. Terman A, Brunk UT: Oxidative stress, accumulation of biological ‘garbage’, and aging. Antioxid Redox Signal 2006, 8:197–204.

    Article  PubMed  CAS  Google Scholar 

  40. Hesselink RP, Wagenmakers AJ, Drost MR, van der Vusse GJ: Lysosomal dysfunction in muscle with special reference to glycogen storage disease type II. Biochim Biophys Acta 2003, 1637:164–170.

    PubMed  CAS  Google Scholar 

  41. Hesselink RP, Schaart G, Wagenmakers AJ, et al.: Age-related morphological changes in skeletal muscle cells of acid alpha-glucosidase knockout mice. Muscle Nerve 2006, 33:505–513.

    Article  PubMed  CAS  Google Scholar 

  42. Fukuda T, Ahearn M, Roberts A, et al.: Autophagy and mistargeting of therapeutic enzyme in skeletal muscle in Pompe disease. Mol Ther 2006, In press.

  43. Terman A: Catabolic insufficiency and aging. Ann N Y Acad Sci 2006, 1067:27–36.

    Article  PubMed  CAS  Google Scholar 

  44. Dreyfus JC, Poenaru L: Alpha glucosidases in white blood cells, with reference to the detection of acid alpha 1–4 glucosidase deficiency. Biochem Biophys Res Commun 1978, 85:615–622.

    Article  PubMed  CAS  Google Scholar 

  45. Umapathysivam K, Whittle AM, Ranieri E, et al.: Determination of acid alpha-glucosidase protein: evaluation as a screening marker for Pompe disease and other lysosomal storage disorders. Clin Chem 2000, 46:1318–1325.

    PubMed  CAS  Google Scholar 

  46. Ko TM, Hwu WL, Lin YW, et al.: Molecular genetic study of Pompe disease in Chinese patients in Taiwan. Hum Mutat 1999, 13:380–384.

    Article  PubMed  CAS  Google Scholar 

  47. Umapathysivam K, Hopwood JJ, Meikle PJ: Determination of acid alpha-glucosidase activity in blood spots as a diagnostic test for Pompe disease. Clin Chem 2001, 47:1378–1383.

    PubMed  CAS  Google Scholar 

  48. Chamoles NA, Niizawa G, Blanco M, et al.: Glycogen storage disease type II: enzymatic screening in dried blood spots on filter paper. Clin Chim Acta 2004, 347:97–102.

    Article  PubMed  CAS  Google Scholar 

  49. Li Y, Scott CR, Chamoles NA, Ghavami A, et al.: Direct multiplex assay of lysosomal enzymes in dried blood spots for newborn screening. Clin Chem 2004, 50:1785–1796.

    Article  PubMed  CAS  Google Scholar 

  50. Shin YS, Endres W, Unterreithmeier J, et al.: Diagnosis of Pompe’s disease using leukocyte preparations. Kinetic and immunological studies of 1,4-alpha-glucosidase in human fetal and adult tissues and cultured cells. Clin Chim Acta 1985, 148:9–19.

    Article  PubMed  CAS  Google Scholar 

  51. Zhang H, Kallwass H, Young SP, et al.: Comparison of maltose and acarbose as inhibitors of maltase-glucoamylase activity in assaying acid alpha-glucosidase activity in dried blood spots for the diagnosis of infantile Pompe disease. Genet Med 2006, 8:302–306.

    PubMed  CAS  Google Scholar 

  52. Okumiya T, Keulemans JL, Kroos MA, et al.: A new diagnostic assay for glycogen storage disease type II in mixed leukocytes. Mol Genet Metab 2006, 88:22–28.

    Article  PubMed  CAS  Google Scholar 

  53. Jack RM, Gordon C, Scott CR, et al.: The use of acarbose inhibition in the measurement of acid alpha-glucosidase activity in blood lymphocytes for the diagnosis of Pompe disease. Genet Med 2006, 8:307–312.

    Article  PubMed  CAS  Google Scholar 

  54. Swallow DM, Kroos M, Van der Ploeg AT, et al.: An investigation of the properties and possible clinical significance of the lysosomal alpha-glucosidase GAA*2 allele. Ann Hum Genet 1989, 53:177–184.

    PubMed  CAS  Google Scholar 

  55. Meikle PJ, Grasby DJ, Dean CJ, et al.: Newborn screening for lysosomal storage disorders. Mol Genet Metab 2006, 88:307–314.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Arthritis and Rheumatism Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, 9000 Rockville Pike, Clinical Center, Building 10/9N244, Bethesda, MD, 20892, USA

    Nina Raben MD, PhD

Authors
  1. Tokiko Fukuda MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Ashley Roberts BS
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Paul H. Plotz MD
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Nina Raben MD, PhD
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Nina Raben MD, PhD.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Fukuda, T., Roberts, A., Plotz, P.H. et al. Acid alpha-glucosidase deficiency (Pompe disease). Curr Neurol Neurosci Rep 7, 71–77 (2007). https://doi.org/10.1007/s11910-007-0024-4

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11910-007-0024-4

Keywords

Search

Navigation