TY - JOUR T1 - Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II. JF - J Inherit Metab Dis Y1 - 2010 A1 - Bembi, Bruno A1 - Pisa, Federica Edith A1 - Confalonieri, Marco A1 - Ciana, Giovanni A1 - Fiumara, Agata A1 - Parini, Rossella A1 - Rigoldi, Miriam A1 - Moglia, Arrigo A1 - Costa, Alfredo A1 - Carlucci, Annalisa A1 - Danesino, Cesare A1 - Pittis, Maria Gabriela A1 - Dardis, Andrea A1 - Ravaglia, Sabrina KW - Adolescent KW - Adult KW - Age of Onset KW - Aged KW - alpha-Glucosidases KW - Child KW - Enzyme Replacement Therapy KW - Female KW - Follow-Up Studies KW - Glycogen Storage Disease Type II KW - Humans KW - Male KW - Middle Aged KW - Observation KW - Time Factors KW - Treatment Outcome KW - Young Adult AB -

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.

VL - 33 IS - 6 U1 - http://www.ncbi.nlm.nih.gov/pubmed/20838899?dopt=Abstract ER -