Molecular basis of infantile reversible cytochrome c oxidase deficiency myopathy

Brain. 2009 Nov;132(Pt 11):3165-74. doi: 10.1093/brain/awp221. Epub 2009 Aug 31.


Childhood-onset mitochondrial encephalomyopathies are usually severe, relentlessly progressive conditions that have a fatal outcome. However, a puzzling infantile disorder, long known as 'benign cytochrome c oxidase deficiency myopathy' is an exception because it shows spontaneous recovery if infants survive the first months of life. Current investigations cannot distinguish those with a good prognosis from those with terminal disease, making it very difficult to decide when to continue intensive supportive care. Here we define the principal molecular basis of the disorder by identifying a maternally inherited, homoplasmic m.14674T>C mt-tRNA(Glu) mutation in 17 patients from 12 families. Our results provide functional evidence for the pathogenicity of the mutation and show that tissue-specific mechanisms downstream of tRNA(Glu) may explain the spontaneous recovery. This study provides the rationale for a simple genetic test to identify infants with mitochondrial myopathy and good prognosis.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Base Sequence
  • Cytochrome-c Oxidase Deficiency* / genetics
  • Cytochrome-c Oxidase Deficiency* / pathology
  • Cytochrome-c Oxidase Deficiency* / physiopathology
  • Diagnosis, Differential
  • Female
  • Genotype
  • Humans
  • Infant
  • Infant, Newborn
  • Male
  • Mitochondria / metabolism
  • Mitochondrial Encephalomyopathies* / genetics
  • Mitochondrial Encephalomyopathies* / pathology
  • Mitochondrial Encephalomyopathies* / physiopathology
  • Molecular Biology
  • Molecular Sequence Data
  • Muscle, Skeletal / pathology
  • Nucleic Acid Conformation
  • Pedigree
  • Phenotype
  • Point Mutation*
  • Prognosis