Mechanism for Valproate Encephalopathy

Sin,—Hyperglycinsemia, hyperglycinuria,l propionicaciduria2 and Reye’s syndrome3 have been reported in epileptic patients taking the anticonvulsant drug valproic acid (VPA). While investigating possible mechanisms of VPA toxicity we found increased plasma glycine and propionic acid concentrations in symptom-free patients taking VPA (table i). With informed consent, loading tests with 500 mg VPA orally were done in three children who had experienced severe vomiting, lethargy, or coma while on VPA. Plasma propionate rose from baseline 5 to 82 nmol/1 (case 1), 21 to 81 nmol/1 (case 2), and 14 to 62 nmol/1 (case 3) by 3 h after the dose. However, these data did not explain why some children became ill from VPA; these levels of glycine and propionate are not nearly as high