The objective of this study was to describe a large Italian cohort of patients with late-onset glycogen storage disease type 2 (GSDII) at various stages of disease progression and to evaluate the clinical effectiveness of alglucosidase alpha enzyme replacement therapy (ERT). Previous studies showed in late-onset patients ERT efficacy against placebo and variable response in uncontrolled studies. Seventy-four juvenile or adult GSDII patients were treated with ERT in a multicenter open label, non-randomized study, from 12 months up to 54 months. Recombinant human alpha glucosidase (rh-GAA) was injected by intravenous route at 20 mg/kg every second week. Patients were divided into three groups according to ERT duration: Group A received treatment for 12-23 months (n = 16), Group B for 24-35 months (n = 14), and Group C for more than 36 months (n = 44). Clinical assessment included a 6-min walk test (6MWT), forced vital capacity (FVC), the Walton and Gardner-Medwin score, the number of hours of ventilation, body mass index, echocardiography and blood creatine kinase (CK). Included in our cohort were 33 males and 41 females (M:F = 0.8:1), with a mean age at first symptoms of 28.3 years (range 2-55 years) and a mean age of 43 years at study entry (range 7-72 years). Seven wheelchair bound patients, as well as 27 patients requiring ventilation support, were included. After treatment we could observe an increase in distance walked on the 6MWT in the large majority of patients (48/58; 83%), with an overall mean increase of 63 m (from 320 ± 161 to 383 ± 178 m). After treatment in the majority of patients FVC was improved or unchanged (45/69; 65%). In ventilated patients we observed an improvement in average number of hours off the ventilator (from 15.6 to 12.1 h). Six patients stopped mechanical ventilation and two others started it. The effect of therapy was not related to ERT duration. Nine of 64 patients (13%) that underwent to echocardiography showed a variable degree of cardiac hypertrophy (left ventriculum or septum), and a positive effect was observed after 36 months of ERT in one adult case. Discontinuation of treatment occurred in four patients: one drop-off case, one patient died for a sepsis after 34 months of treatment and two patients stopped ERT for worsening of general clinical condition. Mild adverse effects were observed in four cases (5%). This study represents the largest cohort of late-onset GSDII patients treated with ERT, and confirm a positive effect of treatment. These results, obtained in a large case series on therapy, indicate a favourable effect of ERT therapy, even in more advanced stage of the disease.

INTRODUCTION:The clinical course of late-onset Pompe disease is heterogeneous, and new clinical outcome measures are needed to evaluate enzyme replacement therapy (ERT).\ud METHODS:We correlated the 6-Minute Walk Test (6MWT), Walton and Gardner-Medwin (WGM) score, and GSGC (Gait, Stairs, Gower, Chair) scores in 40 patients.\ud RESULTS:At baseline, the GSGC score correlated with both WGM (P < 0.001, n = 33) and 6MWT (P < 0.001, n = 26). After 1 year of ERT, we observed a significant change in gait, stairs and chair performance on the GSGC scale. The 6MWT significantly increased from 319 to 371 meters in 32 patients, and the WGM score was reduced.\ud CONCLUSIONS:GSGC is a group of functional tests that requires only a few minutes to perform, therefore, this score might be a good indicator to be used in future studies

Background: Noninvasive ventilation (NIV) may improve quality of sleep but patient-ventilator asynchronies (PVA) may affect sleep structure. Possible changes in ventilation quality after hospital discharge are poorly known. Objective: To analyse the impact of different kinds of PVA on sleep disruption in chronically ventilated neuromuscular patients after in-hospital optimization of ventilator setting with nocturnal polygraphy, and to compare home and hospital PVA occurrence. Methods: Eighteen patients were included in the study. PVA during hospital polygraphic monitoring and during successive home polysomnography were analysed. The relationships between PVA and air leaks, sleep stages, and arousals or awakenings recorded during polysomnography were investigated. Results: Overall, PVA had a low rate of occurrence (4.32 events/h, IQR 1.75e6.25), but their number was higher during home polysomnographies than in hospital (p Z 0.0039): their increase was correlated to an increase in air leaks with respect to hospital monitorings (p Z 0.020). Autotriggerings were the most common asynchronies, followed by ineffective efforts (IE) and prolonged insufflations (PI). All asynchronies occurred more often in NREM than in REM sleep. Autotriggerings and IE were more often associated with arousals than PI (p < 0.05). PVA rate was correlated with arousals and awakenings rate (r Z 0.49, p Z 0.03), but, due to the low PVA rate, only 12.69% of arousals and awakenings were associated with PVA. Conclusions: Most kinds of PVA are often associated with arousals. Polygraphic monitoring may help to improve ventilator setting. However, air leaks and autotriggerings may increase in unassisted environments. Therefore, it may be useful to extend control of NIV effects at home. ª

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