Zidovudine administration during pregnancy and mitochondrial disease in the offspring.
Prophylactic administration of zidovudine (ZDV) to mother-child pairs reduces HIV transmission. ZDV can impair mitochondrial (mt) DNA polymerase gamma, leading to mtDNA depletion. Signs of mitochondrial dysfunction have been observed in a few children with prenatal exposure to nucleoside analogues, although no mtDNA depletion was demonstrated. Other studies failed to confirm mitochondrial disorders in children who were exposed to antiretroviral agents in utero. A child, whose HIV-infected mother received ZDV from the fourth month of pregnancy, developed neonatal encephalomyopathy, anaemia and hyperlactataemia. At 2 weeks of age, a muscle biopsy exhibited red-ragged-like fibres, proliferation of abnormal mitochondria and a 90% depletion of mtDNA without qualitative abnormalities. At 6 months, the depletion was less profound (about 50% of normal values). Severe psychomotor delay and visual disturbances persisted at 30 months, but they were greatly reduced at 5-year follow-up. These laboratory and clinical findings clearly demonstrated that mtDNA alteration was acquired and not consequent to an inherited disorder. Fetal exposure to ZDV may have caused the mtDNA depletion, which, although temporary, led to irreversible but not progressive brain damage.
Tovo
Pier-Angelo
PA
Department of Pediatrics, University of Turin, Turin, Italy. pierangelo.tovo@unito.it
Chiapello
Nadia
N
Gabiano
Clara
C
Zeviani
Massimo
M
Spada
Marco
M
D019380:Anti-HIV Agents / Q000008:administration & dosage / Q000009:adverse effects*; D018890:Chemoprevention; D005260:Female; D015658:HIV Infections / Q000188:drug therapy* / Q000517:prevention & control / Q000635:transmission / Q000821:virology; D006801:Humans; D007231:Infant, Newborn; D018445:Infectious Disease Transmission, Vertical / Q000517:prevention & control; D008297:Male; D028361:Mitochondrial Diseases / Q000139:chemically induced*; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000188:drug therapy* / Q000821:virology; D011256:Pregnancy Outcome; D011297:Prenatal Exposure Delayed Effects; D018894:Reverse Transcriptase Inhibitors / Q000008:administration & dosage / Q000009:adverse effects*; D015215:Zidovudine / Q000008:administration & dosage / Q000009:adverse effects*
D019380:Anti-HIV Agents; D018894:Reverse Transcriptase Inhibitors; D015215:Zidovudine