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. [1]

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. [2]