Pathological Features in Paediatric Patients with TK2 Deficiency.
Cristina JouAndres NascimentoAnna CodinaJulio MontoyaEster López-GallardoSonia EmperadorEduardo Ruiz-PesiniRaquel MonteroDaniel Natera-de BenitoCarlos I OrtezJesus MarquezMaría Victoria ZelayaAlfonso Gutierrez-MataCarmen BadosaLaura Carrera-GarcíaJesica Expósito-EscuderoMonica RoldánYolanda CamaraRamon RamonIsidro FerrerCecilia Jimenez-MallebreraRafael ArtuchPublished in: International journal of molecular sciences (2022)
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.
Keyphrases
- mitochondrial dna
- copy number
- end stage renal disease
- skeletal muscle
- ejection fraction
- newly diagnosed
- chronic kidney disease
- oxidative stress
- prognostic factors
- genome wide
- intensive care unit
- peritoneal dialysis
- gene expression
- single molecule
- heart failure
- ultrasound guided
- dna methylation
- patient reported outcomes
- drug induced
- tyrosine kinase
- protein kinase
- single cell