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         headline: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
         description: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. 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. 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. 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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      headline: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
      description: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. 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. 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. 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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               name:Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy
               type:PostalAddress
            type:Organization
      name:Alessandro Malandrini
      affiliation:
            name:Azienda Ospedaliero-Universitaria Senese
            address:
               name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
               type:PostalAddress
            type:Organization
            name:University of Siena
            address:
               name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
               type:PostalAddress
            type:Organization
      name:Antonio Federico
      affiliation:
            name:Azienda Ospedaliero-Universitaria Senese
            address:
               name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
               type:PostalAddress
            type:Organization
            name:University of Siena
            address:
               name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
               type:PostalAddress
            type:Organization
      name:Maria Teresa Dotti
      affiliation:
            name:Azienda Ospedaliero-Universitaria Senese
            address:
               name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
               type:PostalAddress
            type:Organization
            name:University of Siena
            address:
               name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
               type:PostalAddress
            type:Organization
PostalAddress:
      name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:Department of Neuroscience, Psychology, Drug Research and Child Health, University of Florence, Florence, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy
      name:Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy
      name:Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy
      name:Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy
      name:Department of Clinical and Experimental Medicine, Neurological Institute, University of Pisa, Pisa, Italy
      name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
      name:UOC Neurologia e Malattie Neurometaboliche, Azienda Ospedaliero-Universitaria Senese, Siena, Italy
      name:Department of Medicine, Surgery and Neurosciences, University of Siena, Siena, Italy
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