Researchers at University Hospital, Berne, Switzerland describe the molecular genetic analysis of POLG in a 3.5 years old boy with VPA-induced fatal liver failure and encephalopathy (Alpers-Huttenlocher syndrome, AHS). Mutations in the POLG gene are a common cause of inherited mitochondrial disease in children and adults. They are involved with various neurodegenerative diseases, including Alpers syndrome, and result in accumulation of multiple mtDNA deletions and/or depletions of mtDNA in muscle, brain and liver. Some POLG mutations lead to a range of clinical phenotypes that predispose to fatal liver failure after exposure to VPA. POLG analysis in mitochondrial diseases helps in confirmation of AHS and optimizes clinical management. 
COMMENT. The study extends the list of POLG mutations associated with VPA hepatoxicity. A report of reversible valproate hepatotoxicity due to mutations in mitochondrial DNA polymerase gamma (POLG1) is cited.