RT Journal Article
T1 Deoxynucleoside Therapy for Thymidine Kinase 2-Deficient Myopathy.
A1 Domínguez-González, Cristina
A1 Madruga-Garrido, Marcos
A1 Mavillard, Fabiola
A1 Garone, Caterina
A1 Aguirre-Rodríguez, Francisco Javier
A1 Donati, M Alice
A1 Kleinsteuber, Karin
A1 Martí, Itxaso
A1 Martín-Hernández, Elena
A1 Morealejo-Aycinena, Juan P
A1 Munell, Francina
A1 Nascimento, Andrés
A1 Kalko, Susana G
A1 Sardina, M Dolores
A1 Álvarez Del Vayo, Concepcion
A1 Serrano, Olga
A1 Long, Yuelin
A1 Tu, Yuqi
A1 Levin, Bruce
A1 Thompson, John L P
A1 Engelstad, Kristen
A1 Uddin, Jasim
A1 Torres-Torronteras, Javier
A1 Jimenez-Mallebrera, Cecilia
A1 Martí, Ramon
A1 Paradas, Carmen
A1 Hirano, Michio
AB Thymidine kinase 2, encoded by the nuclear gene TK2, is required for mitochondrial DNA maintenance. Autosomal recessive TK2 mutations cause depletion and multiple deletions of mtDNA that manifest predominantly as a myopathy usually beginning in childhood and progressing relentlessly. We investigated the safety and efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies. We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2-deficient patients under a compassionate use program. In 5 patients with early onset and severe disease, survival and motor functions were better than historically untreated patients. In 11 childhood and adult onset patients, clinical measures stabilized or improved. Three of 8 patients who were nonambulatory at baseline gained the ability to walk on therapy; 4 of 5 patients who required enteric nutrition were able to discontinue feeding tube use; and 1 of 9 patients who required mechanical ventilation became able to breathe independently. In motor functional scales, improvements were observed in the 6-minute walk test performance in 7 of 8 subjects, Egen Klassifikation in 2 of 3, and North Star Ambulatory Assessment in all 5 tested. Baseline elevated serum growth differentiation factor 15 levels decreased with treatment in all 7 patients tested. A side effect observed in 8 of the 16 patients was dose-dependent diarrhea, which did not require withdrawal of treatment. Among 12 other TK2 patients treated with deoxynucleoside, 2 adults developed elevated liver enzymes that normalized following discontinuation of therapy. This open-label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293-303.
YR 2019
FD 2019-06-17
LK http://hdl.handle.net/10668/14012
UL http://hdl.handle.net/10668/14012
LA en
DS RISalud
RD Apr 6, 2025