Depakote (Sodium valproate) is used to treat various types of seizure disorders. It is also used to treat manic episodes related to bipolar disorder (manic depression), and to prevent migraine headaches. Drug toxicity from Depakote is an uncommon but potentially fatal cause of liver injury. Rare mutations in the POLG gene, which codes for the mitochondrial DNA polymerase gamma cause Alpers-Huttenlocher syndrome (AHS). AHS is a neurometabolic disorder associated with an increased risk of developing fatal valproate hepatotoxicity.
In one study1, Heterozygous genetic variation in POLG was strongly associated with valproate-induced liver toxicity (odds ratio = 23.6). These findings implicate impaired liver regeneration in valproate toxicity and show that prospective genetic testing of POLG will identify individuals at high risk of this potentially fatal consequence of treatment.1
Hepatotoxicity, Toxic liver disease, POLG gene, valproate, valproic acid