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Growth Differentiation Factor 15 Is a Novel Diagnostic Biomarker of Mitochondrial Diseases

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Abstract

The present study aimed to investigate whether serum growth differentiation factor 15 concentration is a valuable and reliable diagnostic biomarker of mitochondrial diseases. We examined consecutive patients with mitochondrial diseases, in comparison with patients with non-mitochondrial disease neuromuscular disorders and healthy controls. The serum concentrations of growth differentiation factor 15 were measured by ELISA, and compared with those of FGF21, lactate, and creatine kinase. We also evaluated the correlations between growth differentiation factor 15 concentrations and the Newcastle Mitochondrial Disease Adult Scale, numbers of ragged-red fibers, and COX-negative fibers in the biopsied muscles. The median serum growth differentiation factor 15 concentration was significantly elevated in 42 patients with mitochondrial diseases, compared with 20 patients with non-mitochondrial disease neuromuscular disorders and 50 healthy controls. The area under the curve of growth differentiation factor 15 for the diagnosis of muscle-manifesting mitochondrial diseases was 0.999, in comparison with those area under the curves of the other biomarkers including fibroblast growth factor 21 (0.935, p < 0.01), lactate (0.845 for p < 0.001), and creatine kinase (0.575, p < 0.001). Growth differentiation factor 15 was significantly correlated with mitochondrial disease severity and the proportion of ragged-red fibers identified in the biopsied muscles. Circulating growth differentiation factor 15 measurement is a superior biomarker with high sensitivity and specificity, which can be used as a non-invasive test to screen for primary mitochondrial diseases and dysmetabolic myopathy with associated mitochondrial dysfunction in susceptible individuals.

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Abbreviations

AUC:

Area under ROC curve

COX:

Cytochrome c oxidase

CPEO:

Chronic progressive external ophthalmoplegia

DMD:

Duchenne muscular dystrophy

GDF15:

Growth differentiation factor 15

FGF21:

Fibroblast growth factor 21

IBM:

Inclusion body myositis

MELAS:

Mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes

MERRF:

Myoclonus epilepsy with ragged-red fiber

MM:

Mitochondrial myopathy

MND:

Motoneuron disease

NMDAS:

Newcastle Mitochondrial Disease Adult Scale

MDs:

Mitochondrial diseases

NMDs:

Neuromuscular disorders

RRFs:

Ragged-red fibers

ROC:

Receiver operating characteristics

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Acknowledgements

This study was supported by grants from the National Natural Science Foundation of China (No. 81171182 and No. 81671235). The authors thank the subjects for their participation, referring doctors, and Ms. Dandan Zhao for her assistance with muscle histology.

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Authors and Affiliations

  1. Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China

    Xinbo Ji, Lizhen Zhao, Kunqian Ji, Yuying Zhao, Wei Li, Rui Zhang, Ying Hou & Chuanzhu Yan

  2. Department of Neurology, Yidu Central Hospital of Weifang City, Qingzhou Shi, China

    Lizhen Zhao

  3. Neuropathology Section, WCM Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada

    Jianqiang Lu

  4. Department of Neurology, Qilu Hospital of Shandong University, Key Laboratory for Experimental Teratology of the Ministry of Education, Brain Science Research Institute, Shandong University, No. 107, West Wenhua Road, Jinan, 250012, China

    Chuanzhu Yan

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  1. Xinbo Ji
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Correspondence to Chuanzhu Yan.

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Additional information

Xinbo Ji, Lizhen Zhao, and Kunqian Ji contributed equally to this work.

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Ji, X., Zhao, L., Ji, K. et al. Growth Differentiation Factor 15 Is a Novel Diagnostic Biomarker of Mitochondrial Diseases. Mol Neurobiol 54, 8110–8116 (2017). https://doi.org/10.1007/s12035-016-0283-7

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