title: Respiratory chain deficiency in Alpers syndrome.
abstract: Alpers syndrome is a progressive encephalopathy of early onset, characterized by rapid and severe developmental delay, intractable seizures and liver involvement in a previously healthy child. Here, we report on respiratory chain enzyme deficiency in the liver of four unrelated children presenting with epileptic encephalopathy and liver involvement diagnosed as Alpers syndrome. Interestingly, oxidative phosphorylation in skeletal muscle was normal 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 encephalopathy. Based on these observations, we suggest 1. to give consideration to respiratory chain deficiency in the diagnosis of severe epileptic encephalopathy in childhood, even when no clinical or biological evidence of liver involvement or lactic acidosis is noted, and 2. to investigate the respiratory chain in a needle biopsy of the liver in children with epileptic encephalopathy 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.
authors.affiliation: Department of Medical Genetics and INSERM U-393, Hôpital Necker-Enfants Malades, Paris, France.
authors.forename: M
authors.initials: M
authors.lastname: Gauthier-Villars
authors.forename: P
authors.initials: P
authors.lastname: Landrieu
authors.forename: V
authors.initials: V
authors.lastname: Cormier-Daire
authors.forename: E
authors.initials: E
authors.lastname: Jacquemin
authors.forename: D
authors.initials: D
authors.lastname: Chrétien
authors.forename: A
authors.initials: A
authors.lastname: Rötig
authors.forename: P
authors.initials: P
authors.lastname: Rustin
authors.forename: A
authors.initials: A
authors.lastname: Munnich
authors.forename: P
authors.initials: P
authors.lastname: de Lonlay
mesh_terms: D001284:Atrophy; D001707:Biopsy, Needle; D002540:Cerebral Cortex / Q000473:pathology; D002675:Child, Preschool; D003241:Consanguinity; D003937:Diagnosis, Differential; D002549:Diffuse Cerebral Sclerosis of Schilder / Q000175:diagnosis* / Q000235:genetics / Q000473:pathology; D004579:Electron Transport / Q000235:genetics / Q000502:physiology*; D004798:Enzymes / Q000172:deficiency*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007657:Ketone Bodies / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism; D008099:Liver / Q000473:pathology; D008297:Male; D019289:Pyruvic Acid / Q000378:metabolism; D013226:Status Epilepticus / Q000235:genetics / Q000473:pathology
chemical_list: D004798:Enzymes; D007657:Ketone Bodies; D019344:Lactic Acid; D019289:Pyruvic Acid