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Autosomal recessive\n                      <jats:italic>TK2<\/jats:italic>\n                      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.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>We administered deoxynucleoside monophosphates and deoxynucleoside to 16 TK2\u2010deficient patients under a compassionate use program.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>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\u2010minute 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\u2010dependent 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.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Interpretation<\/jats:title>\n                    <jats:p>This open\u2010label study indicates favorable side effect profiles and clinical efficacy of deoxynucleoside monophosphate and deoxynucleoside therapies for TK2 deficiency. ANN NEUROL 2019;86:293\u2013303<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/ana.25506","type":"journal-article","created":{"date-parts":[[2019,5,24]],"date-time":"2019-05-24T08:50:56Z","timestamp":1558687856000},"page":"293-303","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":126,"title":["Deoxynucleoside Therapy for Thymidine Kinase 2\u2013Deficient Myopathy"],"prefix":"10.1002","volume":"86","author":[{"given":"Cristina","family":"Dom\u00ednguez\u2010Gonz\u00e1lez","sequence":"first","affiliation":[{"name":"Neuromuscular Disorders Unit, Neurology Department Hospital 12 de Octubre  Madrid Spain"},{"name":"Instituto de Investigaci\u00f3n i + 12 Hospital 12 de Octubre  Madrid Spain"},{"name":"Center for Biomedical Network Research on Rare Diseases (CIBERER) Instituto de Salud Carlos III  Madrid Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marcos","family":"Madruga\u2010Garrido","sequence":"additional","affiliation":[{"name":"Neuromuscular Disorders Unit, Pediatric Neurology Department, Instituto de Biomedicina de Sevilla, Hospital U. 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