Medium chain acyl-CoA dehydrogenase deficiency and fatal valproate toxicity.
A boy with delayed psychomotor development, attention deficit disorder, and therapy-resistant epilepsy was treated with valproate. The patient died of liver failure after 4 months of valproate treatment. Postmortem investigation of cultured fibroblasts suggested medium chain acyl-CoA dehydrogenase deficiency, an unexpected finding since the boy had not presented typical manifestations of this disease. Because medium chain acyl-CoA dehydrogenase is an important enzyme in the beta-oxidation of fatty acids, our patient probably had a genetically reduced tolerance to valproate. This drug should be omitted in the treatment of seizures in patients with possible medium chain acyl-CoA dehydrogenase deficiency.
Njølstad
P R
PR
Department of Pediatrics, Haukeland University Hospital, Bergen, Norway.
Skjeldal
O H
OH
Agsteribbe
E
E
Huckriede
A
A
Wannag
E
E
Søvik
O
O
Waaler
P E
PE
D042964:Acyl-CoA Dehydrogenase; D044944:Acyl-CoA Dehydrogenases / Q000172:deficiency*; D000927:Anticonvulsants / Q000009:adverse effects*; D002478:Cells, Cultured; D002648:Child; D004830:Epilepsy, Tonic-Clonic / Q000188:drug therapy* / Q000201:enzymology; D017809:Fatal Outcome; D005347:Fibroblasts / Q000201:enzymology; D006801:Humans; D017093:Liver Failure / Q000139:chemically induced* / Q000201:enzymology; D008297:Male; D012867:Skin / Q000166:cytology / Q000201:enzymology; D014635:Valproic Acid / Q000009:adverse effects*
D000927:Anticonvulsants; D014635:Valproic Acid; D044944:Acyl-CoA Dehydrogenases; D042964:Acyl-CoA Dehydrogenase