Alpers disease is a
neurodegenerative disorder of childhood characterized by early developmental delay, intractable
seizures, and death in childhood. Neuropathologic changes are most severe in the gray matter and consist of diffuse neuronal loss, spongiform changes, and
astrocytosis. We report 2 siblings with
Alpers disease who were discordant for exposure to
valproate (VPA). Both had developmental delay, and a progressive
seizure disorder beginning at 5 years of age. The proband died at age 8 years of complications of ongoing
seizures, including
epilepsia partialis continua, with only minimal liver abnormalities. Her younger brother was treated with VPA for new-onset
seizures and developed
fulminant liver failure 6 months later, which led to his death at 5 years of age. Neuropathologic abnormalities of both siblings were consistent with
Alpers disease. These observations support classification of
Alpers disease and
Alpers disease with
liver cirrhosis as a single disease. They also confirm previous reports indicating that VPA may accelerate
fulminant liver failure in
Alpers disease. We recommend that a diagnosis of
Alpers disease be considered in children with unexplained early developmental delay, cerebellar signs, or
partial seizures, especially
epilepsia partialis continua. When
Alpers disease is strongly suspected, use of VPA should be avoided.