Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders
Open accessAbstract
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.
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GDF15 is considered an indicator of mitochondrial dysfunction in muscle.
“It is considered as an indicator of mitochondrial dysfunction in muscle (21)”
From Human Aging and Longevity Are Characterized by High Levels of Mitokines (2019) · cites this paper as [21]
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- Authors
- Yatsuga, S., Fujita, Y., Ishii, A., Fukumoto, Y., Arahata, H., Kakuma, T., Kojima, T., Ito, M., Tanaka, M., Saiki, R., & Koga, Y.
- Affiliations
- Kurume University (JP)
- Tokyo Metropolitan Institute of Gerontology (JP)
- University of Tsukuba (JP)
- Omuta hospital (JP)
- Toyohashi University of Technology (JP)
- Corresponding author
- Koga, Yasutoshi
- ORCID
- Venue
- Annals of Neurology
- Publisher
- Wiley
- Published
- 2015-10-14
- Volume
- 78
- Issue
- 5
- Pages
- 814-823
- ISSN
- 0364-5134 (ISSN-L)
- 1531-8249
- PMC
- PMC5057301
- OpenAlex
- W1903699046
- Cited by
- 293
- References
- 25
- Citations by year
- 2026: 26 · 2025: 29 · 2024: 29 · 2023: 24 · 2022: 32 · 2021: 35 · 2020: 41 · 2019: 31 · 2018: 14 · 2017: 18 · 2016: 13 · 2013: 1
- FWCI
- 12.59
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Annals of Neurology (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Institutional Repositories DataBase (IRDB) (publishedVersion)
- Terrestrial Environment Research Center (University of Tsukuba) (submittedVersion)
- Funders
- Ministry of Education, Culture, Sports, Science and Technology (MEXT) (25461571 (to Y.K.), 25860891 (to S.Y.), 25242062 (to M.T.))
- The Ministry of Health, Labor and Welfare of Japan. (24-Nanchi-Ippan-005 (to Y.K.) for Research on Intractable Diseases)
- Topics
- Health Sciences › Medicine › Rheumatology › GDF15 and Related Biomarkers
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Clinical Biochemistry › Metabolism and Genetic Disorders
- Keywords
- growth differentiation factor 15, mitochondrial disease, biomarkers, FGF21, respiratory chain deficiency, serum biomarkers, disease severity, sensitivity and specificity
- MeSH terms
- Adolescent, Adult, Child, Creatine Kinase, Female, Fibroblast Growth Factors, Humans, Male, Middle Aged, ROC Curve, Biomarkers, MELAS Syndrome, Pyruvic Acid, Lactic Acid, Mitochondrial Diseases, Growth Differentiation Factor 15, Young Adult
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