title: Reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1).
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.
authors.affiliation: Newcastle upon Tyne NHS Hospitals Trust, Newcastle upon Tyne, UK. robert.mcfarland@ncl.ac.uk
authors.forename: R
authors.initials: R
authors.lastname: McFarland
authors.forename: G
authors.initials: G
authors.lastname: Hudson
authors.forename: R W
authors.initials: RW
authors.lastname: Taylor
authors.forename: S H
authors.initials: SH
authors.lastname: Green
authors.forename: S
authors.initials: S
authors.lastname: Hodges
authors.forename: P J
authors.initials: PJ
authors.lastname: McKiernan
authors.forename: P F
authors.initials: PF
authors.lastname: Chinnery
authors.forename: V
authors.initials: V
authors.lastname: Ramesh
mesh_terms: D000927:Anticonvulsants / Q000009:adverse effects; D002675:Child, Preschool; D000074002:DNA Polymerase gamma; D004272:DNA, Mitochondrial / Q000235:genetics*; D004259:DNA-Directed DNA Polymerase / Q000235:genetics*; D004827:Epilepsy / Q000175:diagnosis / Q000188:drug therapy; D006801:Humans; D017114:Liver Failure, Acute / Q000139:chemically induced*; D008279:Magnetic Resonance Imaging; D008297:Male; D009154:Mutation; D014635:Valproic Acid / Q000009:adverse effects*
chemical_list: D000927:Anticonvulsants; D004272:DNA, Mitochondrial; D014635:Valproic Acid; D000074002:DNA Polymerase gamma; D004259:DNA-Directed DNA Polymerase; C413027:POLG protein, human