Reversible infantile mitochondrial diseases

J Inherit Metab Dis. 2015 May;38(3):427-35. doi: 10.1007/s10545-014-9784-6. Epub 2014 Nov 19.


Mitochondrial diseases are usually severe and progressive conditions; however, there are rare forms that show remarkable spontaneous recoveries. Two homoplasmic mitochondrial tRNA mutations (m.14674T>C/G in mt-tRNA(Glu)) have been reported to cause severe infantile mitochondrial myopathy in the first months of life. If these patients survive the first year of life by extensive life-sustaining measures they usually recover and develop normally. Another mitochondrial disease due to deficiency of the 5-methylaminomethyl-2-thiouridylate methyltransferase (TRMU) causes severe liver failure in infancy, but similar to the reversible mitochondrial myopathy, within the first year of life these infants may also recover completely. Partial recovery has been noted in some other rare forms of mitochondrial disease due to deficiency of mitochondrial tRNA synthetases and mitochondrial tRNA modifying enzymes. Here we summarize the clinical presentation of these unique reversible mitochondrial diseases and discuss potential molecular mechanisms behind the reversibility. Understanding these mechanisms may provide the key to treatments of potential broader relevance in mitochondrial disease, where for the majority of the patients no effective treatment is currently available.

Publication types

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

MeSH terms

  • Gene Expression
  • Humans
  • Infant
  • Infant, Newborn
  • Liver Failure / genetics*
  • Mitochondrial Diseases / genetics*
  • Mitochondrial Myopathies / genetics*
  • Mutation
  • RNA, Transfer / genetics*
  • Thionucleotides / deficiency*
  • Thionucleotides / genetics*
  • Uracil Nucleotides / deficiency*
  • Uracil Nucleotides / genetics*


  • 5-methylaminomethyl-2-thiouridylate
  • Thionucleotides
  • Uracil Nucleotides
  • RNA, Transfer