title: Growth Differentiation Factor 15 Is a Novel Diagnostic Biomarker of Mitochondrial Diseases.
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.
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Xinbo
authors.initials: X
authors.lastname: Ji
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.|Department of Neurology, Yidu Central Hospital of Weifang City, Qingzhou Shi, China.
authors.forename: Lizhen
authors.initials: L
authors.lastname: Zhao
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Kunqian
authors.initials: K
authors.lastname: Ji
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Yuying
authors.initials: Y
authors.lastname: Zhao
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Rui
authors.initials: R
authors.lastname: Zhang
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Hou
authors.affiliation: Neuropathology Section, WCM Health Sciences Centre, University of Alberta, Edmonton, Alberta, Canada.
authors.forename: Jianqiang
authors.initials: J
authors.lastname: Lu
authors.affiliation: Laboratory of Neuromuscular Disorders and Department of Neurology, Qilu Hospital, Shandong University, Jinan, 250012, China. czyan1964@gmail.com.|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. czyan1964@gmail.com.
authors.forename: Chuanzhu
authors.initials: C
authors.lastname: Yan
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood / Q000378:metabolism; D003430:Cross-Sectional Studies; D005260:Female; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood* / Q000175:diagnosis*; D018482:Muscle, Skeletal / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15
keywords: Biomarker; Growth differentiation factor 15; Histology; Mitochondrial disease; Neuromuscular disorders