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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; 3:58-64MG

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.

Authors+Show Affiliations

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

Pub Type(s)

Journal Article

Language

eng

PubMed ID

26937398

Citation

Gruhn, Kai Michael, et al. "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." Molecular Genetics and Metabolism Reports, vol. 3, 2015, pp. 58-64.
Gruhn KM, Heyer CM, Güttsches AK, et al. 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;3:58-64.
Gruhn, K. M., Heyer, C. M., Güttsches, A. K., Rehmann, R., Nicolas, V., Schmidt-Wilcke, T., ... Kley, R. A. (2015). 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. Molecular Genetics and Metabolism Reports, 3, pp. 58-64. doi:10.1016/j.ymgmr.2015.03.010.
Gruhn KM, et al. 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;3:58-64. PubMed PMID: 26937398.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - 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. AU - Gruhn,Kai Michael, AU - Heyer,Christoph Malte, AU - Güttsches,Anne-Katrin, AU - Rehmann,Robert, AU - Nicolas,Volkmar, AU - Schmidt-Wilcke,Tobias, AU - Tegenthoff,Martin, AU - Vorgerd,Matthias, AU - Kley,Rudolf Andre, Y1 - 2015/04/21/ PY - 2016/3/4/entrez PY - 2016/3/5/pubmed PY - 2016/3/5/medline KW - ERT, enzyme replacement therapy KW - Enzyme replacement therapy KW - LOPD, late onset Pompe disease KW - MRI KW - MRI, magnetic resonance imaging KW - Muscle imaging KW - Muscle volume KW - Myopathy KW - Pompe disease KW - rhGAA, human recombinant alpha-glucosidase SP - 58 EP - 64 JF - Molecular genetics and metabolism reports JO - Mol Genet Metab Rep VL - 3 N2 - 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. SN - 2214-4269 UR - https://www.unboundmedicine.com/medline/citation/26937398/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_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S2214-4269(15)30004-5 DB - PRIME DP - Unbound Medicine ER -