Identifier to cite or link to this item: http://hdl.handle.net/20.500.13003/11879
Late-onset thymidine kinase 2 deficiency: a review of 18 cases
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ISSN: 1750-1172
WOS ID: 000467271200001
Scopus EID: 2-s2.0-85065652720
PMID: 31060578
Embase PUI: L628305371
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Dominguez-Gonzalez, Cristina; Hernandez-Lain, Aurelio; Rivas, Eloy; Hernandez-Voth, Ana; Catalan, Javier Sayas; Fernandez-Torron, Roberto; Fuiza-Luces, Carmen; Garcia Garcia, Jorge; Moris, German; Olive, Montse; Miralles, Frances; Diaz-Manera, Jordi; Caballero, Candela; Mendez-Ferrer, Bosco; Marti, Ramon; Garcia Arumi, Elena; Carmen Badosa, Maria; Esteban, Jesus; Jimenez-Mallebrera, Cecilia; Blazquez Encinar, Alberto; Arenas, Joaquin; Hirano, Michio; Angel Martin, Miguel; Paradas, CarmenPublication date
2019-05-06Document type
review articleCitation
Dominguez-Gonzalez C, Hernandez-Lain A, Rivas E, Hernandez-Voth A, Sayas Catalan J, Fernandez-Torron R, et al. Late-onset thymidine kinase 2 deficiency: a review of 18 cases. Orphanet J Rare Dis. 2019 May 06;14:100.Abstract
BackgroundTK2 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.MethodsWe describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12.ResultsThe mean age of onset was 31years. 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.ConclusionsThe 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.
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https://dx.doi.org/10.1186/s13023-019-1071-zMeSH
ChildMitochondrial Myopathies
Young Adult
Adult
Muscle, Skeletal
Humans
Adolescent
Middle Aged
DNA, Mitochondrial
Muscular Diseases
Male
Mutation
Thymidine Kinase
Female
Late Onset Disorders
Retrospective Studies
DeCS
FemeninoEnfermedades de Inicio Tardío
Enfermedades Musculares
ADN Mitocondrial
Mutación
Timidina Quinasa
Adolescente
Masculino
Humanos
Persona de Mediana Edad
Adulto Joven
Músculo Esquelético
Miopatías Mitocondriales
Niño
Estudios Retrospectivos
Adulto