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

Muscle quality is defined as muscle strength generated per unit muscle mass. If enzyme replacement therapy (ERT) has some effects on type II glycogenosis (GSDII) skeletal muscle pathology, we should be able to measure a change in strength and mass. We conducted a prospective study including 11 patients aged 54.2?±?11.2 years, referring to a single institution and receiving ERT for ≥2 years. Median Walton score was 3 (2.5–6). Lower limb skeletal muscles were assessed by dynamometry and quantitative muscle MRI. Three segments (anterior thigh, posterior thigh, leg) were analysed separately. Clinical-MRI correlations were searched for at T0, T6/T8, and T18/24. Changes in lean and fat body composition were assessed by bioelectrical impedance analysis. We found that the anterior thigh showed the best therapeutic response, with an improvement in muscle quality (muscle mass: +7.5%, p?=?0.035; strength: +45%, p?=?0.002). BMI and lean body mass increased (p?=?0.007). Patients with low BMI showed a better outcome. Intramuscular fat accumulation significantly progressed in spite of ERT (+3.7%, p?=?0.001), especially in the poorly responsive posterior thigh muscles. Both clinical assessment and MRI revealed a definite improvement in the anterior thigh muscles. However, progression of intramuscular fat accumulation during ERT, as well as the limited responsiveness of posterior thigh muscles, suggests the necessity for early treatment intervention. The better outcome of patients with low BMI, if confirmed, may indicate that dietary protocols could be adopted as adjuvant measures to ERT in adult GSDII.