title: Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders.
abstract: OBJECTIVE
  The diagnosis of mitochondrial disorders (MDs) is occasionally difficult because patients often present with solitary, or a combination of, symptoms caused by each organ insufficiency, which may be the result of respiratory chain enzyme deficiency. Growth differentiation factor 15 (GDF-15) has been reported to be elevated in serum of patients with MDs. In this study, we investigated whether GDF-15 is a more useful biomarker for MDs than several conventional biomarkers.
  
  
  METHODS
  We measured the serum levels of GDF-15 and fibroblast growth factor 21 (FGF-21), as well as other biomarkers, in 48 MD patients and in 146 healthy controls in Japan. GDF-15 and FGF-21 concentrations were measured by enzyme-linked immunosorbant assay and compared with lactate, pyruvate, creatine kinase, and the lactate-to-pyruvate ratio. We calculated sensitivity and specificity and also evaluated the correlation based on two rating scales, including the Newcastle Mitochondrial Disease Rating Scale (NMDAS).
  
  
  RESULTS
  Mean GDF-15 concentration was 6-fold higher in MD patients compared to healthy controls (2,711 ± 2,459 pg/ml vs 462.5 ± 141.0 pg/mL; p < 0.001). Using a receiver operating characteristic curve, the area under the curve was significantly higher for GDF-15 than FGF-21 and other conventional biomarkers. Our date suggest that GDF-15 is the most useful biomarker for MDs of the biomarkers examined, and it is associated with MD severity.
  
  
  CONCLUSIONS
  Our results suggest that measurement of GDF-15 is the most useful first-line test to indicate the patients who have the mitochondrial respiratory chain deficiency.
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Shuichi
authors.initials: S
authors.lastname: Yatsuga
authors.affiliation: Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Yasunori
authors.initials: Y
authors.lastname: Fujita
authors.affiliation: Department of Neurology, Faculty of Medicine, University of Tsukuba, Ibaraki, Japan.
authors.forename: Akiko
authors.initials: A
authors.lastname: Ishii
authors.affiliation: Division of Cardiovascular Medicine, Department of Internal Medicine, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Fukumoto
authors.affiliation: Department of Neurology, Neuro-Muscular Center, National Omuta Hospital, Fukuoka, Japan.
authors.forename: Hajime
authors.initials: H
authors.lastname: Arahata
authors.affiliation: Department of Biostatistics, Kurume University Graduate School of Medicine, Kurume, Japan.
authors.forename: Tatsuyuki
authors.initials: T
authors.lastname: Kakuma
authors.affiliation: Health Care Center, Toyohashi University of Technology, Toyohashi, Japan.
authors.forename: Toshio
authors.initials: T
authors.lastname: Kojima
authors.affiliation: Research Team for Mechanism of Aging, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Masafumi
authors.initials: M
authors.lastname: Ito
authors.affiliation: Department of Genomics for Longevity and Health, Tokyo Metropolitan Institute of Gerontology, Tokyo, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Tanaka
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Reo
authors.initials: R
authors.lastname: Saiki
authors.affiliation: Department of Pediatrics and Child Health, Kurume University School of Medicine, Fukuoka, Japan.
authors.forename: Yasutoshi
authors.initials: Y
authors.lastname: Koga
mesh_terms: D000293:Adolescent; D000328:Adult; D015415:Biomarkers / Q000097:blood; D002648:Child; D003402:Creatine Kinase / Q000097:blood; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood; D055436:Growth Differentiation Factor 15 / Q000097:blood* / Q000235:genetics*; D006801:Humans; D019344:Lactic Acid / Q000097:blood; D017241:MELAS Syndrome / Q000235:genetics; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000175:diagnosis / Q000235:genetics*; D019289:Pyruvic Acid / Q000097:blood; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C414620:fibroblast growth factor 21; D019344:Lactic Acid; D005346:Fibroblast Growth Factors; D019289:Pyruvic Acid; D003402:Creatine Kinase