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Title: Late-onset thymidine kinase 2 deficiency: a review of 18 cases
Author: Domínguez González, Cristina
Hernández lain, Aurelio
Rivas, Eloy
Hernández Voth, Ana
Sayas Catalán, Javier
Fernández Torrón, Roberto
Fuiza Luces, Carmen
García García, Jorge
Morís, Germán
Olivé i Plana, Montserrat
Miralles, Francesc
Díaz Manera, Jordi
Caballero, Candela
Méndez Ferrer, Bosco
Martí, Ramon
García Arumi, Elena
Badosa, Carmen
Esteban, Jesús
Jimenez Mallebrera, Cecilia
Blázquez Encinar, Alberto
Arenas, Joaquín
Hirano, Michio
Martin, Miguel Ángel
Paradas, Carmen
Keywords: Mitocondris
Malalties musculars
Muscular diseases
Issue Date: 6-Jan-2019
Publisher: BioMed Central
Abstract: 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.
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It is part of: Orphanet Journal of Rare Diseases, 2019, vol. 14
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Appears in Collections:Articles publicats en revistes (Institut d'lnvestigació Biomèdica de Bellvitge (IDIBELL))

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