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| Pàgina inicial > Articles > Articles publicats > Late-onset thymidine kinase 2 deficiency : |
(Centro de Investigación Biomédica en Red de Enfermedades Raras) (Hospital Universitario Central de Asturias) (Institut d'Investigació Biomèdica de Bellvitge) (Institut d'Investigació Biomèdica Sant Pau) (Hospital Sant Joan de Déu (Barcelona, Catalunya)) (Hospital Universitari Vall d'Hebron. Institut de Recerca) (Hospital Sant Joan de Déu (Barcelona, Catalunya)) (Hospital Universitario 12 de Octubre (Madrid)) (Columbia University Medical Center, New York) (Centro de Investigación Biomédica en Red sobre Enfermedades Neurodegenerativas)| Data: | 2019 |
| Resum: | 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. We describe 18 patients with mitochondrial myopathy due to mutations in the TK2 gene with absence of clinical symptoms until the age of 12. 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. 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. |
| Ajuts: | Instituto de Salud Carlos III PI16-01843 Instituto de Salud Carlos III PI16/00579 Instituto de Salud Carlos III CP09/00011 Instituto de Salud Carlos III PI12/01683 Instituto de Salud Carlos III PMP15/00025 |
| Drets: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Llengua: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Matèria: | TK2 deficiency ; Mitochondrial myopathy ; Multiple deletions |
| Publicat a: | Orphanet Journal of Rare Diseases, Vol. 14 (may 2019) , ISSN 1750-1172 |
