FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders.

TitleFGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders.
Publication TypeJournal Article
Year of Publication2016
AuthorsLehtonen, JM, Forsström, S, Bottani, E, Viscomi, C, Baris, OR, Isoniemi, H, Höckerstedt, K, Österlund, P, Hurme, M, Jylhävä, J, Leppä, S, Markkula, R, Heliö, T, Mombelli, G, Uusimaa, J, Laaksonen, R, Laaksovirta, H, Auranen, M, Zeviani, M, Smeitink, J, Wiesner, RJ, Nakada, K, Isohanni, P, Suomalainen, A
Date Published2016 Nov 29
KeywordsAdult, Aged, 80 and over, Animals, Biomarkers, Disease Models, Animal, Enzyme-Linked Immunosorbent Assay, Female, Fibroblast Growth Factors, Growth Differentiation Factor 15, Humans, Male, Mice, Transgenic, Middle Aged, Mitochondrial Diseases, Muscle, Skeletal, Mutation, RNA, Fungal, Sensitivity and Specificity

OBJECTIVE: To validate new mitochondrial myopathy serum biomarkers for diagnostic use.

METHODS: We analyzed serum FGF21 (S-FGF21) and GDF15 from patients with (1) mitochondrial diseases and (2) nonmitochondrial disorders partially overlapping with mitochondrial disorder phenotypes. We (3) did a meta-analysis of S-FGF21 in mitochondrial disease and (4) analyzed S-Fgf21 and skeletal muscle Fgf21 expression in 6 mouse models with different muscle-manifesting mitochondrial dysfunctions.

RESULTS: We report that S-FGF21 consistently increases in primary mitochondrial myopathy, especially in patients with mitochondrial translation defects or mitochondrial DNA (mtDNA) deletions (675 and 347 pg/mL, respectively; controls: 66 pg/mL, p

CONCLUSIONS: S-FGF21 is a specific biomarker for muscle-manifesting defects of mitochondrial translation, including mitochondrial transfer-RNA mutations and primary and secondary mtDNA deletions, the most common causes of mitochondrial disease. However, normal S-FGF21 does not exclude structural respiratory chain complex or assembly factor defects, important to acknowledge in diagnostics.

CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that elevated S-FGF21 accurately distinguishes patients with mitochondrial myopathies from patients with other conditions, and FGF21 and GDF15 mitochondrial myopathy from other myopathies.

Alternate JournalNeurology
Citation Key10.1212/WNL.0000000000003374
PubMed ID27794108
PubMed Central IDPMC5270510
Grant ListMC_UP_1002/1 / / Medical Research Council / United Kingdom