Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II
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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.
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.
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.
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.
KeywordsVital Capacity Enzyme Replacement Therapy Muscle Enzyme Arterial pCO2 Juvenile Patient
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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