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

Kai Michael Gruhn; Christoph Malte Heyer; Anne-Katrin Güttsches; Robert Rehmann; Volkmar Nicolas; Tobias Schmidt-Wilcke; Martin Tegenthoff; Matthias Vorgerd; Rudolf Andre Kley

doi:10.1016/j.ymgmr.2015.03.010

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

Mol Genet Metab Rep. 2015 Apr 21:3:58-64. doi: 10.1016/j.ymgmr.2015.03.010. eCollection 2015 Jun.

Authors

Kai Michael Gruhn¹, Christoph Malte Heyer², Anne-Katrin Güttsches¹, Robert Rehmann¹, Volkmar Nicolas², Tobias Schmidt-Wilcke¹, Martin Tegenthoff¹, Matthias Vorgerd¹, Rudolf Andre Kley¹

Affiliations

¹ Department of Neurology, Heimer Institute for Muscle Research, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany.
² Institute of Radiology, University Hospital Bergmannsheil, Ruhr-University, Bochum, Germany.

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 (R(2) = 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.

Keywords: ERT, enzyme replacement therapy; Enzyme replacement therapy; LOPD, late onset Pompe disease; MRI; MRI, magnetic resonance imaging; Muscle imaging; Muscle volume; Myopathy; Pompe disease; rhGAA, human recombinant alpha-glucosidase.