标题：Muscle imaging data in late-onset Pompe disease reveal a correlation between the pre-existing degree of lipomatous muscle alterations and the efficacy of long-term enzyme replacement therapy
摘要：Abstract Background Late-onset Pompe disease (LOPD) is a metabolic myopathy caused by mutations in {GAA} and characterized by proximal muscle weakness and respiratory insufficiency. There is evidence from clinical studies that enzyme replacement therapy (ERT) with human recombinant alpha-glucosidase improves motor performance and respiratory function in LOPD. Objective We analyzed quantitative muscle {MRI} data of lower limbs to evaluate the effects of long-term {ERT} on muscle parameters. Methods Three symptomatic {LOPD} patients who received {ERT} for five years and four untreated presymptomatic {LOPD} patients were included in the study. T1-weighted {MRI} images were used to determine volumes of thigh and lower leg muscles. In addition, mean gray values of eight individual thigh muscles were calculated to assess the degree of lipomatous muscle alterations. Results We detected a decrease in thigh muscle volume of 6.7% (p < 0.001) and an increase in lower leg muscle volume of 8.2% (p = 0.049) after five years of ERT. Analysis of individual thigh muscles revealed a positive correlation between the degree of lipomatous muscle alterations at baseline and the increase of gray values after five years of {ERT} (R2 = 0.68, p < 0.001). Muscle imaging in presymptomatic patients showed in one case pronounced lipomatous alteration of the adductor magnus muscle and mild to moderate changes in further thigh muscles. Conclusions The results demonstrate that fatty muscle degeneration can occur before clinical manifestation of muscle weakness and suggest that mildly affected muscles may respond better to {ERT} treatment than severely involved muscles. If these findings can be validated by further studies, it should be discussed if muscle alterations detected by muscle {MRI} may be an objective sign of disease manifestation justifying an early start of {ERT} in clinically asymptomatic patients in order to improve the long-term outcome.
Loading...
