Please use this identifier to cite or link to this item: http://hdl.handle.net/10668/3171
Título : Late-onset thymidine kinase 2 deficiency: a review of 18 cases
Autor : Domínguez-González, Cristina
Hernández-Laín, Aurelio
Rivas, Eloy
Hernández-Voth, Ana
Sayas Catalán, Javier
Fernández-Torrón, Roberto
Fuiza-Luces, Carmen
García García, Jorge
Morís, Germán
Olivé, Montse
Miralles, Frances
Díaz-Manera, Jordi
Caballero, Candela
Méndez-Ferrer, Bosco
Martí, Ramon
García Arumi, Elena
Badosa, María Carmen
Esteban, Jesús
Jimenez-Mallebrera, Cecilia
Blazquez Encinar, Alberto
Arenas, Joaquín
Hirano, Michio
Martin, Miguel Ángel
Paradas, Carmen
Filiación: [Dominguez-Gonzalez,C; Esteban,J] Neurology department, Neuromuscular disorders Unit, 12 de Octubre Hospital, Madrid, Spain. [Dominguez-Gonzalez,C; Fuiza-Luces,C; Esteban,J; Blazquez Encinar,A; Arenas,J; Martin,MA] Research Institute i+12, 12 de Octubre Hospital, Madrid, Spain. [Dominguez-Gonzalez,C; Fuiza-Luces,C; Díaz-Manera,J; Martí,C; García Arumi,E; Esteban,J; Jimenez-Mallebrera,C; Blazquez Encinar,A; Arenas,J; Martin,MA] Biomedical Network Research Centre on Rare Diseases (CIBERER), Instituto de Salud Carlos III, Madrid, Spain. [Hernández-Laín,A] Neuropathology, Pathology Department, Neuromuscular disorders Unit, 12 de Octubre Hospital, Madrid, Spain. [Rivas,E] Pathological Anatomic Department, Neuromuscular Disorders Unit, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain. [Hernández-Voth,A; Sayas Catalán,J] Neumology department, Neuromuscular disorders Unit, 12 de Octubre Hospital, Madrid, Spain. [Fernández-Torrón,R] Neurology Department, Neuromuscular disorders Unit, Hospital de Donostia, San Sebastian, Spain. [Fuiza-Luces,C; Blazquez Encinar,A; Arenas,J; Martin,MA] Mitochondrial and Neuromuscular Diseases Laboratory, Research Institute of Hospital '12 de Octubre' ('i+12'), Madrid, Spain. [García García,J] Neurology Department, Hospital de Albacete, Albacete, Spain. [Morís,G] Neurology Department, Neuromuscular disorders Unit, Hospital Central de Asturias, Oviedo, Spain. [Olivé,M] Pathological Anatomy Department, Neuromuscular disorders unit, IDIBELL-Hospital de Bellvitge, Barcelona, Spain. [Miralles,F] Neurology department, Neuromuscular disorders unit, Hospital Universitari Son Espases, Palma, Spain. [Díaz-Manera,J] Neurology department, Neuromuscular disorders unit, Hospital de la Santa Creu I Sant Pau, Barcelona, Spain. [Caballero,C] Respiratory Department, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío, CSIC, CIBERES, Universidad de Sevilla, Sevilla, Spain. [Méndez-Ferrer,B] Rehabilitation Department, Hospital Virgen del Rocio, Sevilla, Spain. [Martí,R; Badosa,MC; Jimenez-Mallebrera,C] Neuromuscular Unit, Neurology Department, Institut de Recerca Sant Joan de Déu, Hospital Sant Joan de Déu, Barcelona, Spain. [García Arumi,E] Research group on Neuromuscular and Mitochondrial Diseases, Valld'Hebron Research Institute, Universitat Autònoma de Barcelona, Barcelona, Spain. [Hirano,M] Department of Neurology, H. Houston Merritt Center, Columbia University Medical Center, New York, USA. [Paradas,C] Neurology Department, Neuromuscular Disorders Unit, Instituto de Biomedicina de Sevilla, Hospital U. Virgen del Rocío, CSIC, Universidad de Sevilla, Sevilla, Spain. [Paradas,C] Biomedical Network Research Centre on Neurodegenerative Diseases (CIBERNED), Madrid, Spain.
Palabras clave : TK2 deficiency
Mitochondrial myopathy
Multiple deletions
Timidina quinasa
Miopatías mitocondriales
Gene delention
Eliminación de gen
DNA, mitochondrial
ADN mitocondrial
MeSH: Medical Subject Headings::Persons::Persons::Age Groups::Adolescent
Medical Subject Headings::Persons::Persons::Age Groups::Adult
Medical Subject Headings::Persons::Persons::Age Groups::Child
Medical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Nucleic Acids::DNA::DNA, Circular::DNA, Mitochondrial
Medical Subject Headings::Check Tags::Female
Medical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::Humans
Medical Subject Headings::Check Tags::Male
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Middle Aged
Medical Subject Headings::Diseases::Musculoskeletal Diseases::Muscular Diseases::Mitochondrial Myopathies
Medical Subject Headings::Anatomy::Musculoskeletal System::Muscles::Muscle, Skeletal
Medical Subject Headings::Diseases::Musculoskeletal Diseases::Muscular Diseases
Medical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Variation::Mutation
Medical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Epidemiologic Methods::Epidemiologic Study Characteristics as Topic::Epidemiologic Studies::Case-Control Studies::Retrospective Studies
Medical Subject Headings::Chemicals and Drugs::Enzymes and Coenzymes::Enzymes::Transferases::Phosphotransferases::Phosphotransferases (Alcohol Group Acceptor)::Thymidine Kinase
Medical Subject Headings::Persons::Persons::Age Groups::Adult::Young Adult
Fecha de publicación : 6-May-2019
Editorial : BioMed Central Ltd.
Cita Bibliográfica: Domínguez-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.
Abstract: Background: 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.
URI: http://hdl.handle.net/10668/3171
Versión del editor : https://ojrd.biomedcentral.com/articles/10.1186/s13023-019-1071-z
DOI: 10.1186/s13023-019-1071-z
ISSN : 1750-1172 (Online)
Appears in Collections:01- Artículos - Hospital Virgen del Rocío
01- Artículos - IBIS. Instituto de Biomedicina de Sevilla

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