000094553 001__ 94553
000094553 005__ 20210902121738.0
000094553 0247_ $$2doi$$a10.1038/s41598-020-66940-8
000094553 0248_ $$2sideral$$a118601
000094553 037__ $$aART-2020-118601
000094553 041__ $$aeng
000094553 100__ $$aDominguez-Gonzalez, C.
000094553 245__ $$aGrowth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy
000094553 260__ $$c2020
000094553 5060_ $$aAccess copy available to the general public$$fUnrestricted
000094553 5203_ $$aGDF-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.
000094553 540__ $$9info:eu-repo/semantics/openAccess$$aby$$uhttp://creativecommons.org/licenses/by/3.0/es/
000094553 590__ $$a4.379$$b2020
000094553 591__ $$aMULTIDISCIPLINARY SCIENCES$$b17 / 73 = 0.233$$c2020$$dQ1$$eT1
000094553 592__ $$a1.24$$b2020
000094553 593__ $$aMultidisciplinary$$c2020$$dQ1
000094553 655_4 $$ainfo:eu-repo/semantics/article$$vinfo:eu-repo/semantics/publishedVersion
000094553 700__ $$aBadosa, C.
000094553 700__ $$aMadruga-Garrido, M.
000094553 700__ $$aMartí, I.
000094553 700__ $$aParadas, C.
000094553 700__ $$aOrtez, C.
000094553 700__ $$aDiaz-Manera, J.
000094553 700__ $$aBerardo, A.
000094553 700__ $$aAlonso-Pérez, J.
000094553 700__ $$aTrifunov, S.
000094553 700__ $$aCuadras, D.
000094553 700__ $$aKalko, S.G.
000094553 700__ $$aBlázquez-Bermejo, C.
000094553 700__ $$aCámara, Y.
000094553 700__ $$aMartí, R.
000094553 700__ $$aMavillard, F.
000094553 700__ $$aMartin, M.A.
000094553 700__ $$0(orcid)0000-0003-1770-6299$$aMontoya, J.$$uUniversidad de Zaragoza
000094553 700__ $$0(orcid)0000-0002-0269-7337$$aRuiz-Pesini, E.$$uUniversidad de Zaragoza
000094553 700__ $$aVillarroya, J.
000094553 700__ $$aMontero, R.
000094553 700__ $$aVillarroya, F.
000094553 700__ $$aArtuch, R.
000094553 700__ $$aHirano, M.
000094553 700__ $$aNascimento, A.
000094553 700__ $$aJimenez-Mallebrera, C.
000094553 7102_ $$11002$$2060$$aUniversidad de Zaragoza$$bDpto. Bioq.Biolog.Mol. Celular$$cÁrea Bioquímica y Biolog.Mole.
000094553 773__ $$g10 (2020), 10111 1-13$$pSci. rep.$$tScientific Reports$$x2045-2322
000094553 8564_ $$s1865158$$uhttps://zaguan.unizar.es/record/94553/files/texto_completo.pdf$$yVersión publicada
000094553 8564_ $$s492671$$uhttps://zaguan.unizar.es/record/94553/files/texto_completo.jpg?subformat=icon$$xicon$$yVersión publicada
000094553 909CO $$ooai:zaguan.unizar.es:94553$$particulos$$pdriver
000094553 951__ $$a2021-09-02-09:40:31
000094553 980__ $$aARTICLE