A 7-year-old boy developed a severe unilateral grand real 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-l,8-dicarboxylic acid demonstrating the enhanced capacity of omega-oxidation in fatty acid oxidation.