94553 20210902121738.0 doi 10.1038/s41598-020-66940-8 sideral 118601 ART-2020-118601 eng Dominguez-Gonzalez, C. Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy 2020 Access copy available to the general public Unrestricted GDF-15 is a biomarker for mitochondrial diseases. We investigated the application of GDF-15 as biomarker of disease severity and response to deoxynucleoside treatment in patients with thymidine kinase 2 (TK2) deficiency and compared it to FGF-21. GDF-15 and FGF-21 were measured in serum from 24 patients with TK2 deficiency treated 1–49 months with oral deoxynucleosides. Patients were grouped according to age at treatment and biomarkers were analyzed at baseline and various time points after treatment initiation. GDF-15 was elevated on average 30-fold in children and 6-fold in adults before the start of treatment. There was a significant correlation between basal GDF-15 and severity based on pretreatment distance walked (6MWT) and weight (BMI). During treatment, GDF-15 significantly declined, and the decrease was accompanied by relevant clinical improvements. The decline was greater in the paediatric group, which included the most severe patients and showed the greatest clinical benefit, than in the adult patients. The decline of FGF-21 was less prominent and consistent. GDF-15 is a potential biomarker of severity and of therapeutic response for patients with TK2 deficiency. In addition, we show evidence of clinical benefit of deoxynucleoside treatment, especially when treatment is initiated at an early age. info:eu-repo/semantics/openAccess by http://creativecommons.org/licenses/by/3.0/es/ 4.379 2020 MULTIDISCIPLINARY SCIENCES 17 / 73 = 0.233 2020 Q1 T1 1.24 2020 Multidisciplinary 2020 Q1 info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Badosa, C. Madruga-Garrido, M. Martí, I. Paradas, C. Ortez, C. Diaz-Manera, J. Berardo, A. Alonso-Pérez, J. Trifunov, S. Cuadras, D. Kalko, S.G. Blázquez-Bermejo, C. Cámara, Y. Martí, R. Mavillard, F. Martin, M.A. Montoya, J. Universidad de Zaragoza (orcid)0000-0003-1770-6299 Ruiz-Pesini, E. Universidad de Zaragoza (orcid)0000-0002-0269-7337 Villarroya, J. Montero, R. Villarroya, F. Artuch, R. Hirano, M. Nascimento, A. Jimenez-Mallebrera, C. 1002 060 Universidad de Zaragoza Dpto. Bioq.Biolog.Mol. Celular Área Bioquímica y Biolog.Mole. 10 (2020), 10111 1-13 Sci. rep. Scientific Reports 2045-2322 1865158 http://zaguan.unizar.es/record/94553/files/texto_completo.pdf Versión publicada 492671 http://zaguan.unizar.es/record/94553/files/texto_completo.jpg?subformat=icon icon Versión publicada oai:zaguan.unizar.es:94553 articulos driver 2021-09-02-09:40:31 ARTICLE