Abstract
A 16 year old brain damaged girl with 10% activity of carbamyl phosphate synthetase (CPS) maintained NH4 levels of 20-55uM, on ketoacid therapy for 4 years. VPA (20 mg/kg/d) was then started to control akinetic seizures. Plasma NH4 rose from 30 to 226μM in one week. VPA was stopped and reinstituted on 3 other occasions with a similar HA response. During VPA therapy SGOT was 13-27 IU/1, SGPT 9-24 IU/1, bil. 0.4mg/dl. Plasma citrulline fell from 15 ± 1 to 9 ± lμM (SEM) p < .005 on VPA. Plasma glycine remained normal. Plasma NH4 was also measured in 28 epileptic children on VPA and in 29 patients on other anticonvulsants. Plasma NH4 was higher in the VPA group, 33.6 ± 1.9 vs 23.6 ± 1.5, p < .001. Mean plasma VPA level was 11.5 mg/dl, SGOT 23 and SGPT 13. There was no correlation between plasma concentrations of NH4 and VPA. Two adults and one child received VPA (20mg/kg/d) for a period of one week proceeded and followed by 1 week control periods. Plasma NH4 levels before, during and after VPA were: 32.3±3.7, 50.4±4.7, 26.9±3.9 p < .001. Plasma VPA levels were therapeutic and SGOT 18. Thus, VPA therapy resulted in a modest but significant increase in plasma NH4 without evidence of liver damage. It caused symptomatic HA in a patient with impaired waste nitrogen excretion. VPA induced HA may be a result of inhibition of activity of CPS or acetylglutamate synthetase as is thought to occur in certain organic acidemias. These data suggest that NH4+ levels should be monitored in patients receiving VPA.
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Batshaw, M., Valle, D. & Brusilow, S. 1559 DEPAKENE (VPA) INDUCED HYPERAMMONEMIA (HA). Pediatr Res 15 (Suppl 4), 703 (1981). https://doi.org/10.1203/00006450-198104001-01576
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DOI: https://doi.org/10.1203/00006450-198104001-01576