Pathological Features in Paediatric Patients with TK2 Deficiency
Jou, Cristina (Biomedical Center for Research in Rare Diseases CIBERER-ISCIII)
Nascimento, Andres (Biomedical Center for Research in Rare Diseases CIBERER-ISCIII)
Codina, Anna (Hospital Sant Joan de Déu (Manresa))
Montoya, Julio (Universidad de Zaragoza)
López-Gallardo, Ester (Universidad de Zaragoza)
Emperador, Sonia (Universidad de Zaragoza)
Ruiz-Pesini, Eduardo (Universidad de Zaragoza)
Montero, Raquel (Hospital Sant Joan de Déu (Manresa))
Natera-de Benito, Daniel (Hospital Sant Joan de Déu (Manresa))
Ortez González, Carlos Ignacio (Hospital Sant Joan de Déu (Barcelona, Catalunya))
Marquez, Jesus (Hospital Sant Joan de Déu (Manresa))
Zelaya, Maria Victoria (Instituto de Investigación Sanitaria de Navarra)
Gutierrez-Mata, Alfonso (Hospital Nacional Niños "Dr Carlos Sáenz Herrera" (Costa Rica))
Badosa, Carmen (Institut de Recerca Sant Joan de Déu)
Carrera-García, Laura (Institut de Recerca Sant Joan de Déu)
Expósito-Escudero, Jesica (Institut de Recerca Sant Joan de Déu)
Roldan Molina, Mònica (Hospital Sant Joan de Déu (Manresa))
Cámara, Yolanda (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Martí, Ramon A (Hospital Universitari Vall d'Hebron. Institut de Recerca)
Ferrer, Isidro (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Jiménez Mallebrera, Cecilia (Universitat de Barcelona. Departament de Genètica, Microbiologia i Estadística)
Artuch, R (Biomedical Center for Research in Rare Diseases CIBERER-ISCIII, 28029 Madrid, Spain)
Universitat Autònoma de Barcelona

Date:	2022
Abstract:	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.
Grants:	Instituto de Salud Carlos III PI17-00021 Instituto de Salud Carlos III PI17-00166 Instituto de Salud Carlos III PI20-00340
Rights:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Language:	Anglès
Document:	Article ; recerca ; Versió publicada
Subject:	TK2 deficiency ; Paediatric patients ; Ultrastructural studies ; Muscle biopsy ; Mitochondrial myopathies ; Ragged red fibres
Published in:	International journal of molecular sciences, Vol. 23 (september 2022) , ISSN 1422-0067

DOI: 10.3390/ijms231911002
PMID: 36232299

11 p, 7.3 MB

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