Domínguez-González, CristinaHernández-Laín, AurelioRivas, EloyHernández-Voth, AnaSayas Catalán, JavierFernández-Torrón, RobertoFuiza-Luces, CarmenGarcía García, JorgeMorís, GermánOlivé, MontseMiralles, FrancesDíaz-Manera, JordiCaballero, CandelaMéndez-Ferrer, BoscoMartí, RamonGarcía Arumi, ElenaBadosa, María CarmenEsteban, JesúsJimenez-Mallebrera, CeciliaBlazquez Encinar, AlbertoArenas, JoaquínHirano, MichioMartin, Miguel ÁngelParadas, Carmen2020-08-252020-08-252019-05-06Domínguez-González C, Hernández-Laín A, Rivas E, Hernández-Voth A, Sayas Catalán J, Fernández-Torrón R, et al. Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Orphanet J Rare Dis. 2019 May 6;14(1):100.http://hdl.handle.net/10668/3171Background: TK2 gene encodes for mitochondrial thymidine kinase, which phosphorylates the pyrimidine nucleosides thymidine and deoxycytidine. Recessive mutations in the TK2 gene are responsible for the 'myopathic form' of the mitochondrial depletion/multiple deletions syndrome, with a wide spectrum of severity. Methods: We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. Results: The mean age of onset was 31 years. The first symptom was muscle limb weakness in 10/18, eyelid ptosis in 6/18, and respiratory insufficiency in 2/18. All patients developed variable muscle weakness during the evolution of the disease. Half of patients presented difficulty in swallowing. All patients showed evidence of respiratory muscle weakness, with need for non-invasive Mechanical Ventilation in 12/18. Four patients had deceased, all of them due to respiratory insufficiency. We identified common radiological features in muscle magnetic resonance, where the most severely affected muscles were the gluteus maximus, semitendinosus and sartorius. On muscle biopsies typical signs of mitochondrial dysfunction were associated with dystrophic changes. All mutations identified were previously reported, being the most frequent the in-frame deletion p.Lys202del. All cases showed multiple mtDNA deletions but mtDNA depletion was present only in two patients. Conclusions: The late-onset is the less frequent form of presentation of the TK2 deficiency and its natural history is not well known. Patients with late onset TK2 deficiency have a consistent and recognizable clinical phenotype and a poor prognosis, due to the high risk of early and progressive respiratory insufficiency.enTK2 deficiencyMitochondrial myopathyMultiple deletionsTimidina quinasaMiopatías mitocondrialesGene delentionEliminación de genDNA, mitochondrialADN mitocondrialMedical Subject Headings::Persons::Persons::Age Groups::AdolescentMedical Subject Headings::Persons::Persons::Age Groups::AdultMedical Subject Headings::Persons::Persons::Age Groups::ChildMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Circular::DNA, MitochondrialMedical Subject Headings::Check Tags::FemaleMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Check Tags::MaleMedical Subject Headings::Persons::Persons::Age Groups::Adult::Middle AgedMedical Subject Headings::Diseases::Musculoskeletal Diseases::Muscular Diseases::Mitochondrial MyopathiesMedical Subject Headings::Anatomy::Musculoskeletal System::Muscles::Muscle, SkeletalMedical Subject Headings::Diseases::Musculoskeletal Diseases::Muscular DiseasesMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::MutationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective StudiesMedical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Thymidine KinaseMedical Subject Headings::Persons::Persons::Age Groups::Adult::Young Adultresearch article31060578open access10.1186/s13023-019-1071-z1750-1172PMC6501326