RT Journal Article
T1 Growth Differentiation Factor 15 is a potential biomarker of therapeutic response for TK2 deficient myopathy.
A1 Dominguez-Gonzalez, Cristina
A1 Badosa, Carmen
A1 Madruga-Garrido, Marcos
A1 Martí, Itxaso
A1 Paradas, Carmen
A1 Ortez, Carlos
A1 Diaz-Manera, Jordi
A1 Berardo, Andres
A1 Alonso-Pérez, Jorge
A1 Trifunov, Selena
A1 Cuadras, Daniel
A1 Kalko, Susana G
A1 Blázquez-Bermejo, Cora
A1 Cámara, Yolanda
A1 Martí, Ramon
A1 Mavillard, Fabiola
A1 Martin, Miguel A
A1 Montoya, Julio
A1 Ruiz-Pesini, Eduardo
A1 Villarroya, Joan
A1 Montero, Raquel
A1 Villarroya, Francesc
A1 Artuch, Rafael
A1 Hirano, Michio
A1 Nascimento, Andrés
A1 Jimenez-Mallebrera, Cecilia
AB 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.
YR 2020
FD 2020-06-22
LK http://hdl.handle.net/10668/15798
UL http://hdl.handle.net/10668/15798
LA en
DS RISalud
RD Apr 11, 2025