Premium
Long‐term observational, non‐randomized study of enzyme replacement therapy in late‐onset glycogenosis type II
Author(s) -
Bembi Bruno,
Pisa Federica Edith,
Confalonieri Marco,
Ciana Giovanni,
Fiumara Agata,
Parini Rossella,
Rigoldi Miriam,
Moglia Arrigo,
Costa Alfredo,
Carlucci Annalisa,
Danesino Cesare,
Pittis Maria Gabriela,
Dardis Andrea,
Ravaglia Sabrina
Publication year - 2010
Publication title -
journal of inherited metabolic disease
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.462
H-Index - 102
eISSN - 1573-2665
pISSN - 0141-8955
DOI - 10.1007/s10545-010-9201-8
Subject(s) - enzyme replacement therapy , juvenile , glycogen storage disease type ii , medicine , cardiology , disease , biology , genetics
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 pCO 2 ), 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 pCO 2 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.