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Journal of Inherited Metabolic Disease

, Volume 33, Issue 6, pp 727–735 | Cite as

Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II

  • Bruno Bembi
  • Federica Edith Pisa
  • Marco Confalonieri
  • Giovanni Ciana
  • Agata Fiumara
  • Rossella Parini
  • Miriam Rigoldi
  • Arrigo Moglia
  • Alfredo Costa
  • Annalisa Carlucci
  • Cesare Danesino
  • Maria Gabriela Pittis
  • Andrea Dardis
  • Sabrina Ravaglia
Original Article

Abstract

Objectives

Type II glycogenosis (GSDII) is a lysosomal storage disorder due to acid alpha-glucosidase (GAA) deficiency. Enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase (rhGAA) has been demonstrated to be effective in the treatment of infantile forms of GSDII, but little information is available concerning late-onset phenotypes. Long-term follow-up studies are not available at present. The aim of this study was to evaluate the ERT long-term effects in late-onset GSDII.

Methods

Twenty-four patients, including 7 juveniles and 17 adults, received bi-weekly infusion of rhGAA (20 mg/kg) for at least 36 months. Clinical conditions, muscular function (6-min walking test, 6MWT; Walton scale, WS), respiratory function (vital capacity, VC; forced expiratory volume, FEV1; arterial pCO2), and muscle enzymes were assessed every 6 months.

Results

The 6MWT improved in both juvenile and adult patients (p = 0.01, p = 0.0002, respectively), as well as in patients with moderate to severe muscle function impairment (WS > 3.5; p = 0.002). An overall improvement in WS was also observed (p = 0.0003). VC and FEV1 remained unchanged, while pCO2 decreased (p = 0.017). Muscle enzymes decreased significantly (p < 0.0001). Two patients (8%) showed transient secondary events during ERT.

Conclusions

Long-term ERT with rhGAA was shown to be safe, well tolerated, and effective in improving motor function and in stabilizing respiratory function in late-onset GSDII. The response pattern showed a progressive clinical improvement during the follow-up period in juvenile patients, while in adults it reached and maintained a plateau after the first year of treatment.

Keywords

Vital Capacity Enzyme Replacement Therapy Muscle Enzyme Arterial pCO2 Juvenile Patient 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.

Notes

Acknowledgments

This work was supported by the Agenzia Italiana del Farmaco (AIFA) D.G. 62229; by I.R.C.C.S. Burlo Garofolo-Trieste, RC 92/05; by a grant from “Programma Italia-USA”-526D/47 of the Istituto Superiore di Sanità, Rome; and by a grant from the Italian Association of Glycogenosis (AIG). The authors wish to thank the participating patients and their families for their precious contribution to data collection and clinical information and Sarah Tripepi Winteringham, MCIL, for her assistance in manuscript editing.

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Copyright information

© SSIEM and Springer 2010

Authors and Affiliations

  • Bruno Bembi
    • 1
  • Federica Edith Pisa
    • 2
  • Marco Confalonieri
    • 3
  • Giovanni Ciana
    • 1
  • Agata Fiumara
    • 4
  • Rossella Parini
    • 5
  • Miriam Rigoldi
    • 5
  • Arrigo Moglia
    • 6
  • Alfredo Costa
    • 6
  • Annalisa Carlucci
    • 7
  • Cesare Danesino
    • 8
  • Maria Gabriela Pittis
    • 9
  • Andrea Dardis
    • 1
  • Sabrina Ravaglia
    • 6
  1. 1.Regional Coordination Centre for Rare DiseasesUniversity Hospital Santa Maria della MisericordiaUdineItaly
  2. 2.Institute of Hygiene and Clinical EpidemiologyUniversity Hospital Santa Maria della MisericordiaUdineItaly
  3. 3.Pulmonary UnitUniversity Hospital of TriesteTriesteItaly
  4. 4.Paediatric ClinicUniversity of CataniaCataniaItaly
  5. 5.Metabolic Unit, Paediatric DepartmentSan Gerardo HospitalMonzaItaly
  6. 6.Department of Neurological SciencesUniversity of PaviaPaviaItaly
  7. 7.Respiratory Intensive Care Unit, IRCCS Fondazione MaugeriPaviaItaly
  8. 8.Medical GeneticsUniversity of PaviaPaviaItaly
  9. 9.Metabolic Unit, I.R.C.C.S. Burlo Garofolo of TriesteTriesteItaly

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