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Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase γ (POLG1)

Newcastle upon Tyne NHS Hospitals Trust, Newcastle upon Tyne, UK.
Archives of Disease in Childhood (Impact Factor: 2.91). 03/2008; 93(2):151-3. DOI: 10.1136/adc.2007.122911
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ABSTRACT We report the case of a 2-year-old boy with seizures who developed hepatic failure shortly after commencing sodium valproate. Unexpectedly, liver function returned to normal on stopping the drug. Sequencing of the mitochondrial polymerase gamma gene (POLG1) revealed four heterozygous substitutions, two of which have been identified in cases of Alpers-Huttenlocher disease.

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    • "Valproic acid, although seemingly beneficial for SE, should be avoided, as patients with POLG1 mutations are at high risk of acute liver failure, which can manifest several weeks after starting therapy. Transient liver failure with recovery after stopping valproic acid is possible (Patient 5) and has been reported (McFarland et al., 2008). In case of irreversible organ failure, transplantation rescues liver function, but neurologic outcome remains grim. "
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