Progressive Reversion of Clinical and Molecular Phenotype in a Child With Liver Mitochondrial DNA Depletion

J Hepatol. 2002 May;36(5):698-703. doi: 10.1016/s0168-8278(02)00021-1.


Mitochondrial DNA depletion is a well established cause of severe liver failure in infancy. The autosomal inheritance of this quantitative mitochondrial DNA defect supports the involvement of a nuclear gene in the control of mitochondrial DNA level. We previously described a case of a 28-month-old child presenting with a progressive liver fibrosis due to a mitochondrial DNA depletion (85% at 12 months of age). As this syndrome was clinically liver-restricted, a liver transplant was initially discussed. We report the clinical, biochemical and molecular follow-up of this child, now 6 years old. The patient displayed a spontaneous gradual improvement of his liver function with continuous increment of clotting factor values since 32 months of age. A marked reduction of the previous extensive fibrosis was evidenced on a liver biopsy performed at 46 months of age associated with a dramatic decrease of the mitochondrial DNA depletion (35%). Consequently, an almost complete restoration of respiratory chain activities containing mitochondrial DNA-encoded subunits was observed. This is the first report of a revertant phenotype in liver mitochondrial DNA depletion syndrome.

Publication types

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

MeSH terms

  • Biopsy
  • Child
  • DNA, Mitochondrial / genetics*
  • Electron Transport / physiology
  • Humans
  • Liver Cirrhosis / etiology
  • Liver Cirrhosis / genetics*
  • Liver Cirrhosis / pathology
  • Male
  • Mitochondria / physiology*
  • Mitochondrial Diseases / complications
  • Mitochondrial Diseases / genetics*
  • Phenotype
  • Recovery of Function / genetics*


  • DNA, Mitochondrial