Cámara Navarro, YolandaCarreño-Gago, LidiaMartín, Miguel A.Melià, Maria J.Blázquez, AlbertoDelmiro, AitorGarrabou Tornos, GlòriaMorén Núñez, ConstanzaDíaz-Manera, JorgeGallardo, EduardoBornstein, BelénLópez Gallardo, EsterHernández-Lain, AurelioSan Millán, BeatrizCancho, EstherRodríguez Vico, JaimeMartí, RamonGarcía Arumí, Elena2025-02-202025-02-202015-05-060028-3878https://hdl.handle.net/2445/219048Thymidine kinase 2 (TK2) is a mitochondrial enzyme participating in the salvage of deoxyribonucleotides needed for mitochondrial DNA (mtDNA) replication. TK2 catalyzes the first and rate-limiting step of the deoxypyrimidine salvage pathway. Mutations in TK2 were typically associated with a severe myopathic form of mtDNA depletion syndrome (MDS) characterized by a dramatic decrease in mtDNA copy number in muscle that manifests during infancy and leads to the early death of most patients.1 Recently, several patients have been diagnosed with a late-onset or slow-progressing form of the disease manifesting as a milder myopathy with mtDNA multiple deletions.2–5 Here we describe 7 adult cases presenting with a mild myopathy compatible with a relatively normal life for decades and associated with multiple mtDNA deletions and no marked depletion in skeletal muscle. TK2 activity was drastically reduced in cultured fibroblasts of 2 of these patients, suggesting that redundant or complementary biochemical mechanisms could bypass the defect in some individuals, in contrast with severely affected infantile patients.3 p.application/pdfeng(c) American Academy of Neurology, 2015ProteïnesFibroblastsMalalties muscularsProteinsFibroblastsMuscular Diseasesinfo:eu-repo/semantics/article6617322025-02-20info:eu-repo/semantics/openAccess