Outcome Measures in Juvenile/Adult GSDII Cases

Abstract

Delineation of the natural history of patients with the heterogeneous juvenile/adult form of glycogen storage disease type II (GSDII) is needed to evaluate enzyme replacement therapy (ERT) efficacy. In natural history data, a progressive decline in skeletal and respiratory muscle function has been observed over the years before ERT. Several outcome measures were evaluated before and during ERT, such as muscle strength evaluated by Medical Research Council (MRC) scale, a series of timed and graded functional tests such as Gait, Stairs, Gowers, Chair (GSGC) score, the Brooke score for upper arms, the Six-Minute Walk Test (6MWT), forced vital capacity on spirometry determined both in lying and sitting position, and quality of life evaluated by SF-36. We critically evaluated the 6MWT as a primary outcome measure to evaluate patient performance. However, the 6MWT is not useful for wheelchair bound patients, patients using a walker or in ventilator-dependent patients. The previously mentioned outcome measures were further monitored in a series of patients at different time points during ERT. Evidence was found of a partial improvement in the time needed to complete functional GSGC tests in some cases during a prolonged observational study. However, after 6 months, the time needed to complete some functional tests increased after the initial improvement. The use of different functional parameters seems crucial to determine the efficacy of ERT, since not all juvenile/adult patients respond similarly over time. The relative prevalence and clinical heterogeneity of juvenile/adult GSDII cases shows the importance of a critical evaluation of clinical parameters used as outcome measures, both for multicentre observational studies or future clinical trials. A protocol valid for long-term studies is useful to confirm the presence of clinical efficacy.