Clinical and molecular spectrum of thymidine kinase 2-related mtDNA maintenance defect

Mol Genet Metab. 2018 Jun;124(2):124-130. doi: 10.1016/j.ymgme.2018.04.012. Epub 2018 Apr 28.


Mitochondrial DNA maintenance (mtDNA) defects have a wide range of causes, each with a set of phenotypes that overlap with many other neurological or muscular diseases. Clinicians face the challenge of narrowing down a long list of differential diagnosis when encountered with non-specific neuromuscular symptoms. Biallelic pathogenic variants in the Thymidine Kinase 2 (TK2) gene cause a myopathic form of mitochondrial DNA maintenance defect. Since the first description in 2001, there have been 71 patients reported with 42 unique pathogenic variants. Here we are reporting 11 new cases with 5 novel pathogenic variants. We describe and analyze a total of 82 cases with 47 unique TK2 pathogenic variants in effort to formulate a comprehensive molecular and clinical spectrum of TK2-related mtDNA maintenance disorders.

Keywords: Adult-onset; Early-onset; Mitochondrial DNA maintenance syndrome; Thymidine kinase 2.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adolescent
  • Adult
  • Aged
  • Child
  • Child, Preschool
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Middle Aged
  • Mitochondria / genetics*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Diseases / pathology*
  • Muscular Diseases / genetics*
  • Muscular Diseases / pathology*
  • Mutation*
  • Prognosis
  • Thymidine Kinase / genetics*
  • Young Adult


  • DNA, Mitochondrial
  • thymidine kinase 2
  • Thymidine Kinase

Supplementary concepts

  • Mitochondrial DNA Depletion Syndrome, Myopathic Form