Six children with refractory seizures and focal neuronal damage who died of liver failure are reported from the Washington University School of Medicine, St Louis, MO.
Six children with refractory seizures and focal neuronal damage who died of liver failure are reported from the Washington University School of Medicine, St Louis, MO. Four were treated with valproic acid (VPA) and developed liver failure within 30 - 68 days. Two of these children each had one sibling who was not exposed to VPA and developed the same clinical picture, but liver failure was delayed. Siblings receiving VPA survived only 3 and 5 months after onset of seizures, whereas those not treated with VPA lived for 7 to 16 months. [1]
COMMENT. The authors propose that many of the reported patients with VPA-associated hepatotoxicity represent undiagnosed hepato-cerebral degeneration, the Huttenlocher variant of Alpers’ syndrome. Their experience suggests that liver failure is accelerated by exposure to VPA, and an alternative antiepileptic treatment should be employed in young children with resistant seizures and mental and motor regression, indicative of cerebral degeneration. Recurrence of this syndrome in family members suggests an autosomal recessive inheritance, but the biochemical basis remains undetermined. Of 13 similar cases reported from the Hospital for Sick Children, London [2], only 4 had received VPA and 2 may have died from VPA-hepatotoxicity.(See Ped Neur Briefs July1987)
BickneseARMayWHickeyWFDodsonWEEarly childhood hepatocerebral degeneration misdiagnosed as valproate hepatotoxicityAnn Neurol1992Dec3267677510.1002/ana.4103206101471867EggerJHardingBNBoydSGWilsonJErdohaziMProgressive neuronal degeneration of childhood (PNDC) with liver diseaseClin Pediatr (Phila)1987Apr2641677310.1177/0009922887026004012435443