|Title||FGF21 is a biomarker for mitochondrial translation and mtDNA maintenance disorders.|
|Publication Type||Journal Article|
|Year of Publication||2016|
|Authors||Lehtonen, 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 Published||2016 Nov 29|
|Keywords||Adult, 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.
|PubMed Central ID||PMC5270510|
|Grant List||MC_UP_1002/1 / / Medical Research Council / United Kingdom|