A comparison of genetic mitochondrial disease and nucleoside analogue toxicity. Does fetal nucleoside toxicity underlie reports of mitochondrial disease in infants born to women treated for HIV infection?

Ann N Y Acad Sci. 2000 Nov;918:247-61. doi: 10.1111/j.1749-6632.2000.tb05494.x.


Recent reports of mitochondrial disease in infants whose mothers were treated in pregnancy with nucleoside analogues are of concern. Chronic nucleoside analogue treatment of adults has long been known to cause mitochondrial DNA depletion with the risk of multisystem disease. Combination nucleoside analogue treatment regimens may have the greatest risk of toxicity. This paper briefly presents the underlying biochemical etiologies and phenotypes of some common genetic mitochondrial diseases in order to provide a comparison with reports of infant toxicity. A standardized method for the diagnosis and evaluation of mitochondrial disease is discussed. A hypothesis, with predictions of the effects of antenatal nucleoside analogue treatment on the fetus, is presented and future directions for research on this problem are suggested.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Anti-HIV Agents / adverse effects*
  • Female
  • HIV Infections / drug therapy
  • HIV Infections / prevention & control*
  • HIV Infections / transmission
  • Humans
  • Infant, Newborn
  • Infectious Disease Transmission, Vertical / prevention & control*
  • Mitochondria / drug effects
  • Mitochondria / metabolism
  • Mitochondrial Myopathies / chemically induced*
  • Mitochondrial Myopathies / classification
  • Mitochondrial Myopathies / genetics*
  • Pregnancy
  • Pregnancy Complications / drug therapy*
  • Prenatal Exposure Delayed Effects*
  • Zidovudine / adverse effects*


  • Anti-HIV Agents
  • Zidovudine