RT Journal Article
T1 Late-onset thymidine kinase 2 deficiency: a review of 18 cases
A1 Domínguez-González, Cristina
A1 Hernández-Laín, Aurelio
A1 Rivas, Eloy
A1 Hernández-Voth, Ana
A1 Sayas Catalán, Javier
A1 Fernández-Torrón, Roberto
A1 Fuiza-Luces, Carmen
A1 García García, Jorge
A1 Morís, Germán
A1 Olivé, Montse
A1 Miralles, Frances
A1 Díaz-Manera, Jordi
A1 Caballero, Candela
A1 Méndez-Ferrer, Bosco
A1 Martí, Ramon
A1 García Arumi, Elena
A1 Badosa, María Carmen
A1 Esteban, Jesús
A1 Jimenez-Mallebrera, Cecilia
A1 Blazquez Encinar, Alberto
A1 Arenas, Joaquín
A1 Hirano, Michio
A1 Martin, Miguel Ángel
A1 Paradas, Carmen
K1 TK2 deficiency
K1 Mitochondrial myopathy
K1 Multiple deletions
K1 Timidina quinasa
K1 Miopatías mitocondriales
K1 Gene delention
K1 Eliminación de gen
K1 DNA, mitochondrial
K1 ADN mitocondrial
AB 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.
PB BioMed Central Ltd.
YR 2019
FD 2019-05-06
LK http://hdl.handle.net/10668/3171
UL http://hdl.handle.net/10668/3171
LA en
NO 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.
DS RISalud
RD Apr 11, 2025