Pathological features in paediatric patients with TK2 deficiency

Jou, C. ; Nascimento, A. ; Codina, A. ; Montoya, J. ; López-Gallardo, E. (Universidad de Zaragoza) ; Emperador, S. (Universidad de Zaragoza) ; Ruiz-Pesini, E. (Universidad de Zaragoza) ; Montero, R. ; Natera-de Benito, D. ; Ortez, C. I. ; Márquez, J. ; Zelaya, M. V. ; Gutiérrez-Mata, A. ; Badosa, C. ; Carrera-García, L. ; Expósito-Escudero, J. ; Roldán, M. ; Cámara, Y. ; Marti, R. ; Ferrer, I. ; Jiménez-Mallebrera, C. ; Artuch, R.

Resumen: Thymidine kinase (TK2) deficiency causes mitochondrial DNA depletion syndrome. 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.

Idioma: Inglés

DOI: 10.3390/ijms231911002

Año: 2022

Publicado en: International Journal of Molecular Sciences 23, 19 (2022), 11002[11 pp.]
ISSN: 1661-6596

Factor impacto JCR: 5.6 (2022)

Categ. JCR: BIOCHEMISTRY & MOLECULAR BIOLOGY rank: 66 / 285 = 0.232 (2022) - Q1 - T1
Categ. JCR: CHEMISTRY, MULTIDISCIPLINARY rank: 52 / 178 = 0.292 (2022) - Q2 - T1

Factor impacto CITESCORE: 7.8 - Biochemistry, Genetics and Molecular Biology (Q1) - Computer Science (Q1) - Chemistry (Q1) - Chemical Engineering (Q1) - Medicine (Q1)

Factor impacto SCIMAGO: 1.154 - Medicine (miscellaneous) (Q1) - Physical and Theoretical Chemistry (Q1) - Computer Science Applications (Q1) - Inorganic Chemistry (Q1) - Spectroscopy (Q1) - Organic Chemistry (Q1) - Molecular Biology (Q2) - Catalysis (Q2)

Financiación: info:eu-repo/grantAgreement/ES/DGA/B33-20R
Financiación: info:eu-repo/grantAgreement/ES/FIS/PI17-00021
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI17-00166
Financiación: info:eu-repo/grantAgreement/ES/ISCIII/FIS/PI20-00340

Tipo y forma: Artículo (Versión definitiva)

Área (Departamento): Area Histología (Dpto. Anatom.Histolog.Humanas)
Área (Departamento): Área Bioquímica y Biolog.Mole. (Dpto. Bioq.Biolog.Mol. Celular)