title: A comparison of current serum biomarkers as diagnostic indicators of mitochondrial diseases.
abstract: OBJECTIVE
  To directly compare the diagnostic utility of growth differentiation factor-15 (GDF-15) with our previous fibroblast growth factor-21 (FGF-21) findings in the same adult mitochondrial disease cohort.
  
  
  METHODS
  Serum GDF-15 levels were measured using a quantitative ELISA. Statistical analyses of GDF-15 data were compared with our published FGF-21 findings.
  
  
  RESULTS
  Median serum GDF-15 concentrations were elevated in patients with mitochondrial disease and differed between all experimental groups, mirroring group results for FGF-21. There was a difference between patients diagnosed by muscle biopsy and genetic diagnosis, suggesting that serum GDF-15 measurement may be more broadly specific for mitochondrial disease than for muscle manifesting mitochondrial disease, in contrast to FGF-21. GDF-15 showed a markedly higher diagnostic odds ratio when compared with FGF-21 (75.3 vs 45.7), was a better predictor of disease based on diagnostic sensitivity (77.8% vs 68.5%), and outperformed FGF-21 on receiver operating characteristic curve analysis (area under the curve 94.1% vs 91.1%). Combining both biomarkers did not improve the area under the curve remarkably over GDF-15 alone. GDF-15 was the best predictor of mitochondrial disease (p < 0.002) following multivariate logistic regression analysis.
  
  
  CONCLUSIONS
  GDF-15 outperforms FGF-21 as an indicator of mitochondrial diseases. Our data suggest that GDF-15 is generally indicative of inherited mitochondrial disease regardless of clinical phenotype, whereas FGF-21 seems to be more indicative of mitochondrial disease when muscle manifestations are present.
  
  
  METHODS
  This study provides Class III evidence that serum GDF-15 accurately distinguishes patients with mitochondrial diseases from those without them.
authors.affiliation: From the Department of Neurogenetics (R.L.D., C.M.S.), Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, Sydney, Australia; and the Department of Neurology (C.L., C.M.S), Royal North Shore Hospital, Sydney, Australia.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Davis
authors.affiliation: From the Department of Neurogenetics (R.L.D., C.M.S.), Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, Sydney, Australia; and the Department of Neurology (C.L., C.M.S), Royal North Shore Hospital, Sydney, Australia.
authors.forename: Christina
authors.initials: C
authors.lastname: Liang
authors.affiliation: From the Department of Neurogenetics (R.L.D., C.M.S.), Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital, Sydney, Australia; and the Department of Neurology (C.L., C.M.S), Royal North Shore Hospital, Sydney, Australia. carolyn.sue@sydney.edu.au.
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Sue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019540:Area Under Curve; D015415:Biomarkers / Q000097:blood; D001706:Biopsy; D001774:Blood Chemical Analysis; D015331:Cohort Studies; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005346:Fibroblast Growth Factors / Q000097:blood*; D055436:Growth Differentiation Factor 15 / Q000097:blood*; D006801:Humans; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood* / Q000235:genetics / Q000473:pathology; D015999:Multivariate Analysis; D009132:Muscles / Q000473:pathology; D016017:Odds Ratio; D012372:ROC Curve; D055815:Young Adult
chemical_list: D015415:Biomarkers; C526140:GDF15 protein, human; D055436:Growth Differentiation Factor 15; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors