Two novel cosegregating mutations in tRNAMet and COX III, in a patient with exercise intolerance and autoimmune polyendocrinopathy

Mitochondrion. 2009 Apr;9(2):123-9. doi: 10.1016/j.mito.2009.01.006. Epub 2009 Jan 21.


We report a 12-year-old patient with growth retardation, exercise intolerance, lactic acidosis (increasing after exercise) and autoimmune polyendocrinopathy type 2. Muscle biopsy shows abundant COX-negative fibers, subsarcolemmal mitochondrial aggregates and markedly reduced activities of all respiratory chain complexes. Genetic analysis identified two new cosegregating mutations in Met-tRNA (m.4415A>G) and Cox III (m.9922A>C), located in highly conserved regions of MtDNA. Both the mutations are heteroplasmics in multiple patients' tissues. Single-muscle fiber analysis showed significantly higher levels of both the mutations in COX-negative than in normal fibers. In addition, a possible link between the mitochondrial dysfunction and the autoimmune disease is suggested.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acidosis, Lactic / genetics*
  • Child
  • DNA, Mitochondrial / genetics*
  • Female
  • Humans
  • Mitochondria / pathology
  • Mitochondrial Proteins / metabolism
  • Muscles / pathology
  • Point Mutation*
  • Polyendocrinopathies, Autoimmune / genetics*
  • Prostaglandin-Endoperoxide Synthases / genetics*
  • Prostaglandin-Endoperoxide Synthases / metabolism
  • RNA, Transfer, Met / genetics*


  • DNA, Mitochondrial
  • Mitochondrial Proteins
  • RNA, Transfer, Met
  • Prostaglandin-Endoperoxide Synthases
  • cyclooxygenase-3