title: Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II.
abstract: OBJECTIVE
  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.
authors.affiliation: Regional Coordination Centre for Rare Diseases, University Hospital Santa Maria della Misericordia, Piazzale Santa Maria della Misericordia 15, 33100 Udine, Italy. bembi.bruno@aoud.sanita.fvg.it
authors.forename: Bruno
authors.initials: B
authors.lastname: Bembi
authors.forename: Federica Edith
authors.initials: FE
authors.lastname: Pisa
authors.forename: Marco
authors.initials: M
authors.lastname: Confalonieri
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ciana
authors.forename: Agata
authors.initials: A
authors.lastname: Fiumara
authors.forename: Rossella
authors.initials: R
authors.lastname: Parini
authors.forename: Miriam
authors.initials: M
authors.lastname: Rigoldi
authors.forename: Arrigo
authors.initials: A
authors.lastname: Moglia
authors.forename: Alfredo
authors.initials: A
authors.lastname: Costa
authors.forename: Annalisa
authors.initials: A
authors.lastname: Carlucci
authors.forename: Cesare
authors.initials: C
authors.lastname: Danesino
authors.forename: Maria Gabriela
authors.initials: MG
authors.lastname: Pittis
authors.forename: Andrea
authors.initials: A
authors.lastname: Dardis
authors.forename: Sabrina
authors.initials: S
authors.lastname: Ravaglia
mesh_terms: D000293:Adolescent; D000328:Adult; D017668:Age of Onset; D000368:Aged; D002648:Child; D056947:Enzyme Replacement Therapy / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006009:Glycogen Storage Disease Type II / Q000188:drug therapy* / Q000201:enzymology / Q000453:epidemiology / Q000534:rehabilitation; D006801:Humans; D008297:Male; D008875:Middle Aged; D019370:Observation; D013997:Time Factors; D016896:Treatment Outcome; D055815:Young Adult; D000520:alpha-Glucosidases / Q000627:therapeutic use*
chemical_list: D000520:alpha-Glucosidases