Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II.
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.
Bembi
Bruno
B
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
Pisa
Federica Edith
FE
Confalonieri
Marco
M
Ciana
Giovanni
G
Fiumara
Agata
A
Parini
Rossella
R
Rigoldi
Miriam
M
Moglia
Arrigo
A
Costa
Alfredo
A
Carlucci
Annalisa
A
Danesino
Cesare
C
Pittis
Maria Gabriela
MG
Dardis
Andrea
A
Ravaglia
Sabrina
S
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*
D000520:alpha-Glucosidases