Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders

Ann Neurol. 2015 Nov;78(5):814-23. doi: 10.1002/ana.24506. Epub 2015 Oct 14.


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.

Interpretation: 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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Biomarkers / blood
  • Child
  • Creatine Kinase / blood
  • Female
  • Fibroblast Growth Factors / blood
  • Growth Differentiation Factor 15 / blood*
  • Growth Differentiation Factor 15 / genetics*
  • Humans
  • Lactic Acid / blood
  • MELAS Syndrome / genetics
  • Male
  • Middle Aged
  • Mitochondrial Diseases / diagnosis
  • Mitochondrial Diseases / genetics*
  • Pyruvic Acid / blood
  • ROC Curve
  • Young Adult


  • Biomarkers
  • GDF15 protein, human
  • Growth Differentiation Factor 15
  • fibroblast growth factor 21
  • Lactic Acid
  • Fibroblast Growth Factors
  • Pyruvic Acid
  • Creatine Kinase