Respiratory chain deficiency in Alpers syndrome

Alpers syndrome is a progressive encephalopathy of early onset, characteriz ed by rapid and severe developmental delay, intractable seizures and liver involvement in a previously healthy child. Here, we report on respiratory c hain enzyme deficiency in the liver of four unrelated children presenting w ith epileptic encephalopathy and liver involvement diagnosed as Alpers synd rome. Interestingly, oxidative phosphorylation in skeletal muscle was norma l in 4/4 and blood and CSF lactate in 3/4 patients. Liver involvement had a late clinical onset in patients with previously isolated epileptic encepha lopathy. Based on these observations, we suggest 1. to give consideration t o respiratory chain deficiency in the diagnosis of severe epileptic encepha lopathy in childhood, even when no clinical or biological evidence of liver involvement or lactic acidosis is noted, and 2. to investigate the respira tory chain in a needle biopsy of the liver in children with epileptic encep halopathy prior to valproate administration if biochemical indications for respiratory chain disease or hepatic disturbance are noted, as this drug is believed to occasionally trigger hepatic failure and fatal outcome.