Enzyme Replacement Therapy in Juvenile and Adult Late-Onset Glycogenosis Type II

Abstract

Late-onset glycogenosis type II (Glycogen Storage Disease type II–GSDII) is a rare autosomal disorder caused by deficiency of acid maltase, a lysosomal enzyme that hydrolyses glycogen to glucose. Recently, both infantile and adult GSDII patients have been treated with enzyme replacement therapy (ERT). Important efficacy studies involving large cohorts of juvenile and adult GSDII patients have been recently published or are ongoing; one of them—the Late-Onset Treatment Study (LOTS) study—ran according to a randomised placebo-controlled trial design. According to their clinical outcomes, ERT is effective in modifying the natural course of the disease. Amelioration of motor function measured with the Six-Minute Walk Test (6MWT) and Walton Medwin-Gardner Scale, and stabilisation or mild amelioration of pulmonary function measured with Forced Vital Capacity (FVC) in the upper position, were found in most patients. On the contrary, quality of life measured with SF-36 did not show significant modifications. The above-mentioned clinical parameters may not be adequate in depicting the global clinical status, and their variations do not always correlate with the patients’ clinical feeling during therapy. The 6MWT and FVC may not be the best outcome measures to underscore the clinical modification of the natural course, and other secondary outcomes should be considered. Furthermore, the response to ERT is heterogeneous, as far as the dynamics of response (slow, fast, sustained or plateau), the extent of modifications of the natural course and the functions modified by treatment are concerned. Due to the wide heterogeneity of the disease and the large variability of response, a global parameter is urged in order to identify responder and non-responder patients. The Italian Group on GSDII evaluated efficacy of ERT by a treating-physicians score, ranging from –2 to 2, according to the gain or loss of function (e.g. rising from chair, climbing stairs, walking outside, driving the car, respiratory problems, etc.). The score 0 indicated no ariations, 2 indicated gain/loss of function, 1 the same function but less/more difficulty in performing them. mong the response predictors, the data available suggest that the profile of the responder patient corresponds to female with a lower body mass index (BMI), a better clinical status and shorter disease duration. The reasons for he differing response to ERT are still under investigation, and more studies are needed encompassing subjective nd objective measurements of response.