{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T09:31:25Z","timestamp":1793266285734,"version":"4.5.0"},"reference-count":21,"publisher":"SAGE Publications","issue":"6","license":[{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"},{"start":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T00:00:00Z","timestamp":1775520000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["Journal of Neuromuscular Diseases"],"published-print":{"date-parts":[[2026,11]]},"abstract":"<jats:sec>\n                    <jats:title>Background:<\/jats:title>\n                    <jats:p>\n                      Thymidine kinase 2 (TK2) deficiency is an ultra-rare, severe mitochondrial myopathy caused by pathogenic variants in\n                      <jats:italic toggle=\"yes\">TK2<\/jats:italic>\n                      and characterized by a wide range of ages at onset. The infantile form, presenting before 2 years of age, is the most rapidly progressive and is associated with a high risk of early mortality. We describe the clinical outcomes of early nucleoside therapy in a series of children with infantile-onset TK2 deficiency.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods:<\/jats:title>\n                    <jats:p>We retrospectively reviewed four children with genetically confirmed infantile-onset TK2 deficiency treated with oral deoxycytidine\/deoxythymidine (dC\/dT) through an Early Access Program at two centers. Dosing was escalated to 800\u2005mg\/kg\/day as tolerated. Patients were followed at baseline, Month 1, and regular intervals thereafter. Outcomes included neurological examinations, eight motor milestones, and respiratory and feeding support. Safety laboratory results, neuroimaging, and biopsy findings were reviewed.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results:<\/jats:title>\n                    <jats:p>Treatment began at 19\u201324 months (median duration 26 months; range: 4\u201381). All presented within the first year with hypotonia, motor regression, and respiratory and\/or bulbar involvement. Two required invasive ventilation and three required tube feeding before therapy. After dC\/dT initiation, all improved with no further milestone loss. Three achieved independent ambulation and stair climbing; the fourth, at 4 months of therapy, has begun unassisted walking. Both tracheostomized patients were weaned from ventilation, and enteral feeding was discontinued in all three within 1\u20136 months. Only mild dose-related diarrhea occurred in one patient.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion:<\/jats:title>\n                    <jats:p>Early nucleoside therapy halts disease progression and restores motor function in infantile-onset TK2 deficiency, the most severe form of the disease.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1177\/22143602261433223","type":"journal-article","created":{"date-parts":[[2026,4,7]],"date-time":"2026-04-07T10:09:20Z","timestamp":1775556560000},"page":"1326-1333","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":1,"title":["Transforming the natural course of infantile onset thymidine kinase 2 deficiency through early nucleoside replacement therapy"],"prefix":"10.1177","volume":"13","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5149-9310","authenticated-orcid":false,"given":"Gulcin","family":"Akinci","sequence":"first","affiliation":[{"name":"Department of Pediatrics, Division of Pediatric Neurology, Dr. Behcet Uz Children's Hospital, Izmir Faculty of Medicine, University of Health Sciences, Izmir, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-6878-8150","authenticated-orcid":false,"given":"Javid","family":"Sardarzada","sequence":"additional","affiliation":[{"name":"Leyla Medical Center"},{"name":"Interdisciplinary Neuroscience Department, Institute of Health Sciences, Bolu Abant \u0130zzet Baysal University, Bolu, Turkey"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haluk","family":"Topaloglu","sequence":"additional","affiliation":[{"name":"Yeditepe University Faculty of 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