Abnormal metabolism of carnitine and valproate in a case of acute encephalopathy during chronic valproate therapy.
We analyzed the urinary metabolic profiles of valproate (VPA) and carnitine metabolism in an epileptic patient who died of acute encephalopathy during VPA therapy. On admission, the serum free carnitine level was greatly decreased and gas chromatographic mass spectrometric analysis of organic acids in urine showed a complete lack of beta-oxidation metabolites of VPA, while omega-oxidation was markedly increased. After administration of L-carnitine, the levels of acylcarnitine in both serum and urine, and of serum free carnitine increased, and the metabolites of beta-oxidation appeared in urine, while there was no improvement in the liver and renal functions. This is not a typical case of VPA-induced hepatotoxicity and the main cause of the disease is not clear. But the results show that the mitochondrial beta-oxidation of VPA was greatly disturbed in this patient, which may be related to the carnitine deficiency induced by the chronic VPA-therapy.
Murakami
K
K
Department of Pediatrics, Kansai Medical University, Osaka, Japan.
Sugimoto
T
T
Nishida
N
N
Kobayashi
Y
Y
Kuhara
T
T
Matsumoto
I
I
D001927:Brain Diseases / Q000378:metabolism*; D002331:Carnitine / Q000097:blood / Q000378:metabolism* / Q000652:urine; D002547:Cerebral Palsy / Q000150:complications / Q000378:metabolism; D002648:Child; D002908:Chronic Disease; D005260:Female; D008401:Gas Chromatography-Mass Spectrometry; D006801:Humans; D010084:Oxidation-Reduction; D012640:Seizures / Q000188:drug therapy; D014635:Valproic Acid / Q000009:adverse effects* / Q000378:metabolism / Q000652:urine
D014635:Valproic Acid; D002331:Carnitine