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Late-onset thymidine kinase 2 deficiency: A review of 18 cases

Lookup NU author(s): Professor Jordi Diaz ManeraORCiD



This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


© 2019 The Author(s).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.

Publication metadata

Author(s): Dominguez-Gonzalez C, Hernandez-Lain A, Rivas E, Hernandez-Voth A, Sayas Catalan J, Fernandez-Torron R, Fuiza-Luces C, Garcia Garcia J, Moris G, Olive M, Miralles F, Diaz-Manera J, Caballero C, Mendez-Ferrer B, Marti R, Garcia Arumi E, Badosa MC, Esteban J, Jimenez-Mallebrera C, Encinar AB, Arenas J, Hirano M, Martin MA, Paradas C

Publication type: Review

Publication status: Published

Journal: Orphanet Journal of Rare Diseases

Year: 2019

Volume: 14

Issue: 1

Online publication date: 06/05/2019

Acceptance date: 17/04/2019

ISSN (electronic): 1750-1172

Publisher: BioMed Central Ltd.


DOI: 10.1186/s13023-019-1071-z

PubMed id: 31060578