Late-onset thymidine kinase 2 deficiency: a review of 18 cases
[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...
| Autores: | , , , , , , , , , , , , , , , , , , , , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | Consejo Superior de Investigaciones Científicas (CSIC) |
| Repositorio: | DIGITAL.CSIC. Repositorio Institucional del CSIC |
| OAI Identifier: | oai:digital.csic.es:10261/204934 |
| Acceso en línea: | http://hdl.handle.net/10261/204934 |
| Access Level: | acceso abierto |
| Palabra clave: | TK2 deficiency Mitochondrial myopathy Multiple deletions |
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oai:digital.csic.es:10261/204934 |
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Late-onset thymidine kinase 2 deficiency: a review of 18 casesDomínguez‐González, CristinaHernández-Laín, AurelioRiva, EloyHernández-Voth, AnaSayas Catalán, JavierFernández-Torrón, RobertoFuiza-Luces, CarmenGarcía-García, JorgeMoris, GermánOlivé, MontseMiralles, FrancesDíaz-Manera, JordiCaballero-Eraso, CandelaMéndez-Ferrer, BoscoMartí, RamónGarcía Arumi, ElenaBadosa, María CarmenEsteban, JesúsJiménez-Mallebrera, CeciliaBlázquez Encinar, AlbertoArenas, JoaquínHirano, MichioMartín, Miguel ÁngelParadas, CarmenTK2 deficiencyMitochondrial myopathyMultiple deletions[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.This work was supported by research grants of Plan Nacional de I + D + I and Instituto de Salud Carlos III (ISCIII), Subdirección General de Evaluación y Fomento de la Investigación Sanitaria”, project PI16–01843 (CP), PI16/00579 and CP09/00011 for CJM and the European Regional Development Fund (FEDER a way to achieve Europe). MAM has received funding from the Spanish ISCIII (grant PI 15/00431). A multicentric grant funded by the ISCIII (PMP15/00025 to MAM, RM, MO, CP).Peer reviewedSpringer NatureInstituto de Salud Carlos IIIEuropean CommissionMinisterio de Economía y Competitividad (España)Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72]202020202019info:eu-repo/semantics/articlehttp://purl.org/coar/resource_type/c_6501Publisher's versioninfo:eu-repo/semantics/publishedVersionhttp://hdl.handle.net/10261/204934reponame:DIGITAL.CSIC. Repositorio Institucional del CSICinstname:Consejo Superior de Investigaciones Científicas (CSIC)Ingléshttps://doi.org/10.1186/s13023-019-1071-zSíinfo:eu-repo/semantics/openAccessoai:digital.csic.es:10261/2049342026-05-22T06:33:51Z |
| dc.title.none.fl_str_mv |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| title |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| spellingShingle |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases Domínguez‐González, Cristina TK2 deficiency Mitochondrial myopathy Multiple deletions |
| title_short |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| title_full |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| title_fullStr |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| title_full_unstemmed |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| title_sort |
Late-onset thymidine kinase 2 deficiency: a review of 18 cases |
| dc.creator.none.fl_str_mv |
Domínguez‐González, Cristina Hernández-Laín, Aurelio Riva, Eloy Hernández-Voth, Ana Sayas Catalán, Javier Fernández-Torrón, Roberto Fuiza-Luces, Carmen García-García, Jorge Moris, Germán Olivé, Montse Miralles, Frances Díaz-Manera, Jordi Caballero-Eraso, Candela Méndez-Ferrer, Bosco Martí, Ramón García Arumi, Elena Badosa, María Carmen Esteban, Jesús Jiménez-Mallebrera, Cecilia Blázquez Encinar, Alberto Arenas, Joaquín Hirano, Michio Martín, Miguel Ángel Paradas, Carmen |
| author |
Domínguez‐González, Cristina |
| author_facet |
Domínguez‐González, Cristina Hernández-Laín, Aurelio Riva, Eloy Hernández-Voth, Ana Sayas Catalán, Javier Fernández-Torrón, Roberto Fuiza-Luces, Carmen García-García, Jorge Moris, Germán Olivé, Montse Miralles, Frances Díaz-Manera, Jordi Caballero-Eraso, Candela Méndez-Ferrer, Bosco Martí, Ramón García Arumi, Elena Badosa, María Carmen Esteban, Jesús Jiménez-Mallebrera, Cecilia Blázquez Encinar, Alberto Arenas, Joaquín Hirano, Michio Martín, Miguel Ángel Paradas, Carmen |
| author_role |
author |
| author2 |
Hernández-Laín, Aurelio Riva, Eloy Hernández-Voth, Ana Sayas Catalán, Javier Fernández-Torrón, Roberto Fuiza-Luces, Carmen García-García, Jorge Moris, Germán Olivé, Montse Miralles, Frances Díaz-Manera, Jordi Caballero-Eraso, Candela Méndez-Ferrer, Bosco Martí, Ramón García Arumi, Elena Badosa, María Carmen Esteban, Jesús Jiménez-Mallebrera, Cecilia Blázquez Encinar, Alberto Arenas, Joaquín Hirano, Michio Martín, Miguel Ángel Paradas, Carmen |
| author2_role |
author author author author author author author author author author author author author author author author author author author author author author author |
| dc.contributor.none.fl_str_mv |
Instituto de Salud Carlos III European Commission Ministerio de Economía y Competitividad (España) Consejo Superior de Investigaciones Científicas [https://ror.org/02gfc7t72] |
| dc.subject.none.fl_str_mv |
TK2 deficiency Mitochondrial myopathy Multiple deletions |
| topic |
TK2 deficiency Mitochondrial myopathy Multiple deletions |
| description |
[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. |
| publishDate |
2019 |
| dc.date.none.fl_str_mv |
2019 2020 2020 |
| dc.type.none.fl_str_mv |
info:eu-repo/semantics/article http://purl.org/coar/resource_type/c_6501 Publisher's version info:eu-repo/semantics/publishedVersion |
| format |
article |
| status_str |
publishedVersion |
| dc.identifier.none.fl_str_mv |
http://hdl.handle.net/10261/204934 |
| url |
http://hdl.handle.net/10261/204934 |
| dc.language.none.fl_str_mv |
Inglés |
| language_invalid_str_mv |
Inglés |
| dc.relation.none.fl_str_mv |
https://doi.org/10.1186/s13023-019-1071-z Sí |
| dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
Springer Nature |
| publisher.none.fl_str_mv |
Springer Nature |
| dc.source.none.fl_str_mv |
reponame:DIGITAL.CSIC. Repositorio Institucional del CSIC instname:Consejo Superior de Investigaciones Científicas (CSIC) |
| instname_str |
Consejo Superior de Investigaciones Científicas (CSIC) |
| reponame_str |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
| collection |
DIGITAL.CSIC. Repositorio Institucional del CSIC |
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|
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1869422703646081024 |
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15,81155 |