Abstract
Background and objectiveTK2 deficiency (TK2d) is a rare mitochondrial disorder that manifests predominantly as a progressive myopathy with a broad spectrum of severity and age of onset. The rate of progression is variable, and the prognosis is poor due to early and severe respiratory involvement. Early and accurate diagnosis is particularly important since a specific treatment is under development. This study aims to evaluate the diagnostic value of lower limb muscle MRI in adult patients with TK2d.MethodsWe studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. We compared the identified pattern in patients with TK2d with the MRI pattern of other non-mitochondrial genetic myopathies that share similar clinical characteristics.ResultsWe found a consistent lower limb muscle MRI pattern in patients with TK2d characterized by involvement of the gluteus maximus, gastrocnemius medialis, and sartorius muscles. The identified pattern in TK2 patients differs from the known radiological involvement of other resembling muscle dystrophies that share clinical features.ConclusionsBy analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis.
Highlights
Recessive mutations in the TK2 gene lead to an ultra-rare mitochondrial disorder that manifests primarily as a progressive myopathy with early respiratory involvement [1–4].Cristina Domínguez-González and Roberto Fernández-Torrón contributed to this work.Extended author information available on the last page of the article1 3 Vol:.(1234567890)Mutations in this gene produce a deficiency of the enzyme thymidine kinase 2 (TK2), involved in the intramitochondrial biosynthesis of pyrimidine nucleotides
The gluteus maximus, sartorius, gastrocnemius medialis, semitendinosus, semimembranosus, and tensor fascia latae were the most affected muscles, even though the fat muscle replacement was mild in many cases ((Median Mercuri (MM) 1, range: 0–4)
To study if there were different radiological patterns regarding the molecular diagnosis, we divided the cohort into three different groups: Group 1: patients with an mitochondrial DNA (mtDNA) single large-scale deletion; Group 2: patients with a point mtDNA mutation (MTCO1, MTTL1, MTTK, MTTS1, and MTTN genes); Group 3: patients with mutations in nuclear genes involved in mtDNA synthesis or maintenance (POLG, TWNK, RRM2B, and TK2)
Summary
Recessive mutations in the TK2 gene lead to an ultra-rare mitochondrial disorder that manifests primarily as a progressive myopathy with early respiratory involvement [1–4].Cristina Domínguez-González and Roberto Fernández-Torrón contributed to this work.Extended author information available on the last page of the article1 3 Vol:.(1234567890)Mutations in this gene produce a deficiency of the enzyme thymidine kinase 2 (TK2), involved in the intramitochondrial biosynthesis of pyrimidine nucleotides. The balance in the nucleotide pool is disturbed, which interferes with the synthesis of the mitochondrial DNA (mtDNA), causing mtDNA depletion or multiple mtDNA deletions [5, 6] Clinical symptoms of this mitochondrial disorder can start at any age, with a variable rate of progression. Methods We studied a cohort of 45 genetically confirmed patients with mitochondrial myopathy (16 with mutations in TK2, 9 with mutations in other nuclear genes involved in mitochondrial DNA [mtDNA] synthesis or maintenance, 10 with single mtDNA deletions, and 10 with point mtDNA mutations) to analyze the imaging pattern of fat replacement in lower limb muscles. Conclusions By analyzing the largest cohort of muscle MRI from patients with mitochondrial myopathies studied to date, we identified a characteristic and specific radiological pattern of muscle involvement in patients with TK2d that could be useful to speed up its diagnosis
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
