Abnormal metabolism of valproic acid in fatal hepatic failure
Autor: | A. Schneider, A. Ritz, W. Kochen |
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Rok vydání: | 1983 |
Předmět: |
Male
medicine.medical_specialty medicine.medical_treatment Urine Gastroenterology Peritoneal dialysis Epilepsy Internal medicine medicine Humans Reye Syndrome Child Dicarboxylic aciduria Valproic Acid business.industry Liver Diseases Metabolism medicine.disease Endocrinology Pediatrics Perinatology and Child Health Epilepsy Tonic-Clonic Chemical and Drug Induced Liver Injury business Peritoneal Dialysis medicine.drug Grand mal seizure |
Zdroj: | European Journal of Pediatrics. 141:30-35 |
ISSN: | 1432-1076 0340-6199 |
Popis: | A 7-year-old boy developed a severe unilateral grand mal seizure at the age of 5 years (phenobarbitone therapy); 1.5 years later valproate (2-propylpentanoic acid, VPA) was added to the therapy. After a seizure-free period of 3 months the patient died from hepatic failure resembling Reye syndrome. Several plasma and urine samples from the final stage before and during peritoneal dialysis were analyzed by GC/MS. The predominant feature was the abnormally increased formation of both 3 mono- and 4 double unsaturated metabolites of VPA amounting in plasma to 58%-71% of the sum of VPA plus all analyzed metabolites (controls maximal 15%) and in urine to 34%-61% (controls maximal 10%). The beta-oxidation pathway of VPA was shown to be suppressed (lack of 3-keto-VPA), whereas metabolites from the omega-oxidation pathway could still be measured (urinary 5-OH-VPA plus 2-propylglutaric acid ca. 1.6%, controls more than 10%). 4-en-VPA (2-propyl-4-pentenoic acid) (5%-21% in plasma) and 4,4'-dien-VPA (2(2-propenyl)-4-pentenoic acid) (4%-7%) have been found as abnormal unsaturated metabolites not detectable in controls. Additional typical findings were the high excretion of adipic acid, suberic acid, and 4-octen-1,8-dicarboxylic acid demonstrating the enhanced capacity of omega-oxidation in fatty acid oxidation. |
Databáze: | OpenAIRE |
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