Enzyme replacement therapy improves respiratory outcomes in patients with late-onset type II glycogenosis and high ventilator dependency

PURPOSE: Type II glycogenosis (GSDII) is a rare and often fatal neuromuscular disorder caused by acid alpha-glucosidase deficiency. Although alglucosidase alfa enzyme replacement therapy (ERT) significantly improves outcomes in subjects with the infantile form, its efficacy in patients with the late-onset one is not entirely clear. The long-term efficacy of ERT in late-onset GSGII complicated by severe pulmonary impairment causing high mechanical ventilation dependency was investigated in this study. METHODS: The long-term clinical efficacy of ERT was assessed in eight late-onset GSDII patients using home mechanical ventilation (HMV) by comparing their outcomes with those of six historical control patients (GSDII patients) who had received HMV alone. The number of hospitalizations due to pulmonary exacerbations and of hours of daily use of HMV were considered the study's primary efficacy endpoints. RESULTS: The treatment group showed an increased tendency toward shorter follow-up compared to the control group (35.8 ± 29.2 vs. 52.6 ± 8.55 months; p = 0.04). At the end of the study period, the daily use of HMV (12.5 ± 7.6 vs. 19 ± 14.3 h; p = 0.004) and the hospitalization rate [incidence rate ratio = 0.43 (95 % confidence interval 0.18-0.93); p = 0.03] were significantly lower in the patients receiving ERT. The differences in the forced vital capacity absolute value and percentage change from baseline were not significantly different in the two groups. CONCLUSIONS: ERT reduces ventilator dependency in late-onset GSDII patients and the need for hospitalization due to respiratory exacerbations.