title: Fibroblast growth factor 21 is a sensitive biomarker of mitochondrial disease.
abstract: OBJECTIVE
  To prospectively determine the reliability and validity of serum fibroblast growth factor 21 (FGF-21) as a biomarker for mitochondrial disease in a cross-sectional cohort of adults with mitochondrial disease from a specialist primary care and tertiary referral clinic.
  
  
  METHODS
  We recruited 140 subjects, including 54 adults with mitochondrial disease, 20 patients with nonmitochondrial neuromuscular disease, and 66 control subjects, between November 2011 and October 2012. We compared serum FGF-21 concentrations to classical biomarkers, serum creatine kinase, lactate, pyruvate, and lactate to pyruvate ratio, to determine its validity and reliability as a biomarker of mitochondrial disease. We determined the sensitivity, odds ratio (OR), and overall reliability of FGF-21 as a marker of mitochondrial disease using statistical analyses.
  
  
  RESULTS
  Median serum FGF-21 concentrations were significantly elevated in patients with mitochondrial disease and differed significantly between all experimental groups. FGF-21 showed a markedly higher diagnostic OR (45.7 [95% confidence interval = 12.6-166.5], p < 0.0001) when compared to other biomarkers and was the best predictor of disease according to sensitivity and receiver operating characteristic curve analysis. After multivariate logistic regression analysis controlling for potential confounders, FGF-21 was the only measured parameter capable of predicting mitochondrial disease.
  
  
  CONCLUSIONS
  This prospective study establishes serum FGF-21 levels as a sensitive biomarker of mitochondrial disease and demonstrates that they are the best predictor of this disorder when compared to serum levels of classical indicators: creatine kinase, lactate, pyruvate, and the lactate to pyruvate ratio.
authors.affiliation: From the Department of Neurogenetics (R.L.D., C.L., C.M.S.), Kolling Institute of Medical Research, University of Sydney and Royal North Shore Hospital; and Department of Neurology (C.L., F.E.-H., C.R., M.N., C.M.S.), Royal North Shore Hospital, St. Leonards, NSW, Australia.
authors.forename: Ryan L
authors.initials: RL
authors.lastname: Davis
authors.forename: Christina
authors.initials: C
authors.lastname: Liang
authors.forename: Fabienne
authors.initials: F
authors.lastname: Edema-Hildebrand
authors.forename: Catherine
authors.initials: C
authors.lastname: Riley
authors.forename: Merrilee
authors.initials: M
authors.lastname: Needham
authors.forename: Carolyn M
authors.initials: CM
authors.lastname: Sue
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers; D003430:Cross-Sectional Studies; D005260:Female; D005346:Fibroblast Growth Factors; D006801:Humans; D008297:Male; D008875:Middle Aged; D028361:Mitochondrial Diseases / Q000097:blood*; D009135:Muscular Diseases / Q000097:blood*; D011237:Predictive Value of Tests; D011446:Prospective Studies; D015203:Reproducibility of Results; D055815:Young Adult
chemical_list: D015415:Biomarkers; C414620:fibroblast growth factor 21; D005346:Fibroblast Growth Factors