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Journal of Neurology

, Volume 259, Issue 5, pp 952–958 | Cite as

Observational clinical study in juvenile-adult glycogenosis type 2 patients undergoing enzyme replacement therapy for up to 4 years

  • C. Angelini
  • C. Semplicini
  • S. Ravaglia
  • B. Bembi
  • S. Servidei
  • E. Pegoraro
  • M. Moggio
  • M. Filosto
  • E. Sette
  • G. Crescimanno
  • P. Tonin
  • R. Parini
  • L. Morandi
  • G. Marrosu
  • G. Greco
  • O. Musumeci
  • G. Di Iorio
  • G. Siciliano
  • M. A. Donati
  • F. Carubbi
  • M. Ermani
  • T. Mongini
  • A. Toscano
  • The Italian GSDII Group
Original Communication

Abstract

The objective of this study was to describe a large Italian cohort of patients with late-onset glycogen storage disease type 2 (GSDII) at various stages of disease progression and to evaluate the clinical effectiveness of alglucosidase alpha enzyme replacement therapy (ERT). Previous studies showed in late-onset patients ERT efficacy against placebo and variable response in uncontrolled studies. Seventy-four juvenile or adult GSDII patients were treated with ERT in a multicenter open label, non-randomized study, from 12 months up to 54 months. Recombinant human alpha glucosidase (rh-GAA) was injected by intravenous route at 20 mg/kg every second week. Patients were divided into three groups according to ERT duration: Group A received treatment for 12–23 months (n = 16), Group B for 24–35 months (n = 14), and Group C for more than 36 months (n = 44). Clinical assessment included a 6-min walk test (6MWT), forced vital capacity (FVC), the Walton and Gardner-Medwin score, the number of hours of ventilation, body mass index, echocardiography and blood creatine kinase (CK). Included in our cohort were 33 males and 41 females (M:F = 0.8:1), with a mean age at first symptoms of 28.3 years (range 2–55 years) and a mean age of 43 years at study entry (range 7–72 years). Seven wheelchair bound patients, as well as 27 patients requiring ventilation support, were included. After treatment we could observe an increase in distance walked on the 6MWT in the large majority of patients (48/58; 83%), with an overall mean increase of 63 m (from 320 ± 161 to 383 ± 178 m). After treatment in the majority of patients FVC was improved or unchanged (45/69; 65%). In ventilated patients we observed an improvement in average number of hours off the ventilator (from 15.6 to 12.1 h). Six patients stopped mechanical ventilation and two others started it. The effect of therapy was not related to ERT duration. Nine of 64 patients (13%) that underwent to echocardiography showed a variable degree of cardiac hypertrophy (left ventriculum or septum), and a positive effect was observed after 36 months of ERT in one adult case. Discontinuation of treatment occurred in four patients: one drop-off case, one patient died for a sepsis after 34 months of treatment and two patients stopped ERT for worsening of general clinical condition. Mild adverse effects were observed in four cases (5%). This study represents the largest cohort of late-onset GSDII patients treated with ERT, and confirm a positive effect of treatment. These results, obtained in a large case series on therapy, indicate a favourable effect of ERT therapy, even in more advanced stage of the disease.

Keywords

Glycogenosis type 2 Enzyme replacement therapy Acid maltase Clinical trials 

Notes

Conflict of interest

Drs Toscano and Angelini are members of the Pompe Global Advisory Board, sustained by Genzyme, and received reimbursement for the participation to the board meetings. Drs Angelini, Toscano, Bembi, Servidei, Filosto and Semplicini received support from Genzyme for organizing or participating to scientific meetings.

Supplementary material

415_2011_6293_MOESM1_ESM.pdf (47 kb)
Supplementary material 1 (PDF 46 kb)

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Copyright information

© Springer-Verlag 2011

Authors and Affiliations

  • C. Angelini
    • 1
    • 2
  • C. Semplicini
    • 1
  • S. Ravaglia
    • 3
    • 4
  • B. Bembi
    • 5
  • S. Servidei
    • 6
  • E. Pegoraro
    • 1
  • M. Moggio
    • 7
  • M. Filosto
    • 8
  • E. Sette
    • 9
  • G. Crescimanno
    • 10
  • P. Tonin
    • 11
  • R. Parini
    • 12
  • L. Morandi
    • 13
  • G. Marrosu
    • 14
  • G. Greco
    • 15
  • O. Musumeci
    • 16
  • G. Di Iorio
    • 17
  • G. Siciliano
    • 18
  • M. A. Donati
    • 19
  • F. Carubbi
    • 20
  • M. Ermani
    • 1
  • T. Mongini
    • 21
  • A. Toscano
    • 16
  • The Italian GSDII Group
  1. 1.Department of NeurosciencesUniversity of PadovaPadovaItaly
  2. 2.IRCCS S. CamilloVeniceItaly
  3. 3.Department of Neurological SciencesUniversity of PaviaPaviaItaly
  4. 4.Clinical Institute “Beato Matteo”VigevanoItaly
  5. 5.Regional Coordination Centre for Rare DiseasesUniversity Hospital S. Maria Della MisericordiaUdineItaly
  6. 6.Department of NeurologyUniversità CattolicaRomeItaly
  7. 7.Department of Neurology, Fondazione IRCCS Ca’ Granda Osp. Policlinico, Centro Dino FerrariUniversity of MilanMilanItaly
  8. 8.Clinical Neurology, Section for Neuromuscular Diseases and NeuropathiesUniversity Hospital Spedali CiviliBresciaItaly
  9. 9.Neurology UnitS. Anna HospitalFerraraItaly
  10. 10.Italian National Research CouncilInstitute of Biomedicine and Molecular ImmunologyPalermoItaly
  11. 11.Department of Neurological Sciences and Vision, Section of NeurologyUniversity of VeronaVeronaItaly
  12. 12.Rare Metabolic Diseases Unit, Department of PediatricsSan Gerardo HospitalMonzaItaly
  13. 13.Immunology and Muscular Pathology UnitNational Neurological Institute Carlo BestaMilanItaly
  14. 14.Neuromuscular Unit, Department of Cardiovascular Science and NeurologyUniversity of CagliariSardiniaItaly
  15. 15.Department of NeurosciencesUniversity of SienaSienaItaly
  16. 16.Department of Neurosciences, Psychiatry and AnaesthesiologyUniversity of MessinaMessinaItaly
  17. 17.Department of Neurological SciencesSecond University of NaplesNaplesItaly
  18. 18.Neurological InstituteUniversity of PisaPisaItaly
  19. 19.Clinic of Pediatric NeurologyMeyer HospitalFlorenceItaly
  20. 20.Department of Medicine, Endocrinology, Metabolism and GeriatricsUniversity of Modena and Reggio EmiliaModenaItaly
  21. 21.Centre for Neuromuscular Diseases “P. Peirolo”, Department of NeurosciencesUniversity of TorinoTurinItaly

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