Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression
Articolo
Data di Pubblicazione:
2022
Citazione:
Case Report: Thymidine Kinase 2 (TK2) Deficiency: A Novel Mutation Associated With Childhood-Onset Mitochondrial Myopathy and Atypical Progression / A. Manini, M. Meneri, C. Rodolico, S. Corti, A. Toscano, G.P. Comi, O. Musumeci, D. Ronchi. - In: FRONTIERS IN NEUROLOGY. - ISSN 1664-2295. - 13:(2022), pp. 857279.1-857279.6. [10.3389/fneur.2022.857279]
Abstract:
The nuclear gene TK2 encodes the mitochondrial thymidine kinase, an enzyme involved in the phosphorylation of deoxycytidine and deoxythymidine nucleosides. Biallelic TK2 mutations are associated with a spectrum of clinical presentations mainly affecting skeletal muscle and featuring muscle mitochondrial DNA (mtDNA) instability. Current classification includes infantile- (≤ 1 year), childhood- (1–12 years), and late-onset (≥12 years) forms. In addition to age at onset, these forms differ for progression, life expectancy, and signs of mtDNA instability (mtDNA depletion vs. accumulation of multiple mtDNA deletions). Childhood-onset TK2 deficiency typically causes a rapidly progressive proximal myopathy, which leads to wheelchair-bound status within 10 years of disease onset, and severe respiratory impairment. Muscle biopsy usually reveals a combination of mitochondrial myopathy and dystrophic features with reduced mtDNA content. Here we report the case of an Italian patient presenting childhood-onset, slowly progressive mitochondrial myopathy, ptosis, hypoacusis, dysphonia, and dysphagia, harboring the TK2 variants c.278A>G and c.543del, the latter unreported so far. Compared to other childhood-onset TK2-patients, our case displays atypical features, including slowly progressive muscle weakness and absence of respiratory failure, which are usually observed in late-onset forms. This report extends the genetic background of TK2-related myopathy, highlighting the clinical overlap among different forms.
Tipologia IRIS:
01 - Articolo su periodico
Keywords:
deoxynucleosides; mitochondrial DNA; mtDNA maintenance defects; myopathy; thymidine kinase 2; TK2
Elenco autori:
A. Manini, M. Meneri, C. Rodolico, S. Corti, A. Toscano, G.P. Comi, O. Musumeci, D. Ronchi
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