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We aimed to report the clinical, biochemical, genetic, histopathological, and ultrastructural features of a cohort of paediatric patients with TK2 deficiency. Mitochondrial DNA was isolated from muscle biopsies to assess depletions and deletions. The TK2 genes were sequenced using Sanger sequencing from genomic DNA. All muscle biopsies presented ragged red fibres (RRFs), and the prevalence was greater in younger ages, along with an increase in succinate dehydrogenase (SDH) activity and cytochrome c oxidase (COX)-negative fibres. An endomysial inflammatory infiltrate was observed in younger patients and was accompanied by an overexpression of major histocompatibility complex type I (MHC I). The immunofluorescence study for complex I and IV showed a greater number of fibres than those that were visualized by COX staining. In the ultrastructural analysis, we found three major types of mitochondrial alterations, consisting of concentrically arranged lamellar cristae, electrodense granules, and intramitochondrial vacuoles. The pathological features in the muscle showed substantial differences in the youngest patients when compared with those that had a later onset of the disease. Additional ultrastructural features are described in the muscle biopsy, such as sarcomeric de-structuration in the youngest patients with a more severe phenotype.<\/jats:p>","DOI":"10.3390\/ijms231911002","type":"journal-article","created":{"date-parts":[[2022,9,20]],"date-time":"2022-09-20T22:36:44Z","timestamp":1663713404000},"page":"11002","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Pathological Features in Paediatric Patients with TK2 Deficiency"],"prefix":"10.3390","volume":"23","author":[{"given":"Cristina","family":"Jou","sequence":"first","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres","family":"Nascimento","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Codina","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1770-6299","authenticated-orcid":false,"given":"Julio","family":"Montoya","sequence":"additional","affiliation":[{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IISA), Universidad de Zaragoza, 50011 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ester","family":"L\u00f3pez-Gallardo","sequence":"additional","affiliation":[{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IISA), Universidad de Zaragoza, 50011 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sonia","family":"Emperador","sequence":"additional","affiliation":[{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IISA), Universidad de Zaragoza, 50011 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0269-7337","authenticated-orcid":false,"given":"Eduardo","family":"Ruiz-Pesini","sequence":"additional","affiliation":[{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Instituto de Investigaci\u00f3n Sanitaria de Arag\u00f3n (IISA), Universidad de Zaragoza, 50011 Zaragoza, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0609-5701","authenticated-orcid":false,"given":"Raquel","family":"Montero","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7764-2085","authenticated-orcid":false,"given":"Daniel","family":"Natera-de Benito","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carlos I.","family":"Ortez","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jesus","family":"Marquez","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry 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Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9530-6234","authenticated-orcid":false,"given":"Monica","family":"Rold\u00e1n","sequence":"additional","affiliation":[{"name":"Unitat de Microsc\u00f2pia Confocal i Imatge Cel\u00b7lular, Servei de Medicina Gen\u00e8tica i Molecular, Institut Pedi\u00e0tric de Malaties Rares (IPER), Hospital Sant Joan de D\u00e9u, Esplugues de Llobregat, 08950 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yolanda","family":"Camara","sequence":"additional","affiliation":[{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, Vall d\u2019Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8273-9540","authenticated-orcid":false,"given":"Ramon","family":"Marti","sequence":"additional","affiliation":[{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Research Group on Neuromuscular and Mitochondrial Disorders, Vall d\u2019Hebron Institut de Recerca, Universitat Aut\u00f2noma de Barcelona, 08193 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9888-8754","authenticated-orcid":false,"given":"Isidre","family":"Ferrer","sequence":"additional","affiliation":[{"name":"Department of Pathology and Experimental Therapeutics, University of Barcelona, 08007 Barcelona, Spain"},{"name":"Biomedical Center for Research in Neurodegenerative Diseases (CIBERNED), Bellvitge Institute of Biomedical Research (IDI-BELL), Hospitalet de Llobregat, 08007 Barcelona, Spain"},{"name":"Department of Genetics, Microbiology and Statistics, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8203-7103","authenticated-orcid":false,"given":"Cecilia","family":"Jimenez-Mallebrera","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"},{"name":"Department of Genetics, Microbiology and Statistics, University of Barcelona, 08007 Barcelona, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3422-9685","authenticated-orcid":false,"given":"Rafael","family":"Artuch","sequence":"additional","affiliation":[{"name":"Pathology, Biobank, Pediatric Neurology, Neuromuscular Unit and Clinical Biochemistry Departments, Hospital Sant Joan de D\u00e9u and Institut de Recerca Sant Joan de D\u00e9u, 08950 Barcelona, Spain"},{"name":"Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Zeviani, M., and Viscomi, C. 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