Progressive myofiber loss with extensive fibro-fatty replacement in a child with mitochondrial DNA depletion syndrome and novel thymidine kinase 2 gene mutations

Neuromuscul Disord. 2009 Nov;19(11):784-7. doi: 10.1016/j.nmd.2009.08.002. Epub 2009 Sep 6.


The mitochondrial DNA depletion syndromes (MDS) are autosomal recessive disorders with a decreased mitochondrial DNA copy number. Mutations in thymidine kinase 2 (TK2) have been responsible for the myopathic form of MDS. We describe a child with congenital muscle weakness who had a progressive mitochondrial myopathy associated with extensive fibro-fatty replacement of myofibers resembling muscular dystrophy. MDS was suspected based upon findings in the initial muscle biopsy. Sequence analysis of the TK2 gene revealed two novel heterozygous mutations: the frame shift mutation, c.255_c.258delAGAA, and the heterozygous missense mutation, c.515G>A, (p.R172Q). This report extends the phenotype and genotype of TK2 defects.

Publication types

  • Case Reports

MeSH terms

  • Adolescent
  • Adult
  • Child
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Magnetic Resonance Imaging / methods
  • Male
  • Metabolism, Inborn Errors / genetics
  • Metabolism, Inborn Errors / metabolism
  • Mitochondrial Myopathies / genetics*
  • Mitochondrial Myopathies / pathology*
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / pathology
  • Muscle, Skeletal / ultrastructure
  • Mutation*
  • Thymidine Kinase / genetics*


  • DNA, Mitochondrial
  • thymidine kinase 2
  • Thymidine Kinase