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Fibroblast growth factor 21 and grow differentiation factor 15 are sensitive biomarkers of mitochondrial diseases due to mitochondrial transfer-RNA mutations and mitochondrial DNA deletions

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Abstract

Background

Diagnosis of mitochondrial diseases (MDs) is challenging, since they are multisystemic disorders, characterized by a heterogeneous symptomatology. Recently, an increase in serum levels of fibroblast growth factor 21 (FGF21) and growth differentiation factor 15 (GDF15) has been found in the majority of patients with MDs compared with healthy controls. On the other hand, the finding of low FGF21 and GDF15 levels in some patients with MDs suggests that different types of respiratory chain defects may lead to different profiles of these two proteins.

Objective

In this study, we aimed to validate the diagnostic reliability of FGF21 and GDF15 assays in MDs and to evaluate a possible correlation between serum levels of the two biomarkers with genotype of MD patients. Serum FGF21 and GDF15 levels were measured by a quantitative ELISA.

Results

Our results showed increased serum FGF21 and GDF15 levels in MD patients; however, GDF15 measurement seems to be more sensitive and specific for screening tests for MD than FGF21. Moreover, we showed a positive correlation with both FGF21 and GDF15 levels and the number of COX-negative fibers.

Conclusion

Finally, we also demonstrated that the increase of FGF21 and GDF15 was related to MDs caused by mitochondrial translation defects, and multiple and single mtDNA deletions, but not to MDs due to mutations in the respiratory chain subunits.

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Funding

This work was supported by the University of Siena (Grant 2268-2016-NR-PAR_001). The investigators of Pisa are grateful to Telethon and MITOCON for their support (Grants GSP16001 and GUP09004). IT is research fellow supported by a grant from Regione Toscana (Project: MePreMare-Precision medicine and rare neurological diseases).

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Authors and Affiliations

  1. UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy

    Patrizia Formichi, Alessandro Malandrini, Antonio Federico & Maria Teresa Dotti

  2. Department of Medicine, Surgery and Neurosciences, University of Siena, V.le Bracci, 2, 53100, Siena, Italy

    Patrizia Formichi, Nastasia Cardone, Ilaria Taglia, Elena Cardaioli, Simona Salvatore, Alessandro Malandrini, Antonio Federico & Maria Teresa Dotti

  3. Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy

    Nastasia Cardone

  4. Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy

    Annalisa Lo Gerfo, Costanza Simoncini, Vincenzo Montano, Gabriele Siciliano & Michelangelo Mancuso

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  1. Patrizia Formichi
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  2. Nastasia Cardone
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Correspondence to Patrizia Formichi.

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This study was approved by the local ethics committee, and we obtained written consent from all participants.

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Formichi, P., Cardone, N., Taglia, I. et al. Fibroblast growth factor 21 and grow differentiation factor 15 are sensitive biomarkers of mitochondrial diseases due to mitochondrial transfer-RNA mutations and mitochondrial DNA deletions. Neurol Sci 41, 3653–3662 (2020). https://doi.org/10.1007/s10072-020-04422-5

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  • DOI: https://doi.org/10.1007/s10072-020-04422-5

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