Long-term observational, non-randomized study of enzyme replacement therapy in late-onset glycogenosis type II.

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 pCO2), 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 pCO2 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 lateonset
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.