Enzyme replacement therapy in severe adult-onset glycogen storage disease type II

Abstract

Glycogen storage disease type II (GSDII) is an autosomal recessive myopathy caused by a deficiency of the lysosomal enzyme acid alpha-glucosidase (GAA). Enzyme replacement therapy (ERT) with recombinant GAA (rh-GAA) has become available for GSDII, although its effectiveness in adults remains unknown. We present a case of ERT with rhGAA in a 49-year-old male with GSDII in a severe stage of the disease. Quantitative magnetic resonance imaging showed an increase in muscle mass of the inferior limb, especially evident on the quadriceps femoris and the patient's body weight increased up to 30%, although his reported dietary habits were the same as before ERT. Beyond improvement in muscle strength and respiratory function, we observed a dramatic increase in body mass index from 12.7 to 16.6 kg/m(2). This may reflect a change from a catabolic state to a more balanced metabolic state during ERT.

Changes in nutritional status and body composition during enzyme replacement therapy in adult‐onset type II glycogenosis

“…Morevover, improvement of respiratory function has been claimed to explain the observed improvement in BW in patients treated with ERT [13]. This view is apparently supported by our own findings, since of the three subjects with low BMI, only patient 1, detailed in reference [22], significantly improved respiratory function, and this patient was also the only one significantly improving BW and LM during ERT. We observed a discrepancy between BMI and FM evaluation, since there were five patients with increased FM, and this was an unexpected finding in view of their normal BMI (Table 2). This suggests that BMI assessment in patients with GSDII may underestimate the increase in FM due to altered body composition.…”

“…Morevover, improvement of respiratory function has been claimed to explain the observed improvement in BW in patients treated with ERT [13]. This view is apparently supported by our own findings, since of the three subjects with low BMI, only patient 1, detailed in reference [22], significantly improved respiratory function, and this patient was also the only one significantly improving BW and LM during ERT.…”

Changes in skeletal muscle qualities during enzyme replacement therapy in late‐onset type II glycogenosis: temporal and spatial pattern of mass vs. strength response

“…SCF also increased , especially during the first 6 months of ERT, and so did BMI and percent fat mass. Other authors (Strothotte et al 2010;Merk et al 2009) and our own previous observations (Ravaglia et al 2008(Ravaglia et al , 2010 pointed to an increase in BMI during ERT. Authors tend to interpret the weight gain as a sign of clinical improvement and provide putative explanations, such as decreased movement-related and respiration-related energy expenditure along with clinical motor and respiratory improvement (Ravaglia et al 2010).…”

Skeletal muscle pathology of infantile Pompe disease during long-term enzyme replacement therapy

“…The urinary hexose tetrasaccharide (Hex 4 ) biomarker that is used for overall assessment of disease severity and response to ERT [16,17] does not allow for the evaluation of the extent of involvement of particular muscle groups. Recent work has indicated the potential utility of whole-body magnetic resonance imaging (MRI) [18,19]. However, this technique has not yet been systematically evaluated for its ability to measure subtle changes in muscle pathology and will require further assessment of its diagnostic and prognostic potential in Pompe disease.…”