Valproic acid-induced metabolic imbalance of amino acids and organic acids.
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In two patients receiving valproic acid (VPA) who showed asymptomatic hyperammonemia, plasma amino acids and organic acids were serially determined while the dosage of VPA was reduced weekly.The patient M. M. is a 21-year-old female with cerebral palsy and generalized tonic clonic convulsion (GTC). She was born prematurely (36 weeks, 1400g) and had neonatal distress. She developed the first convulsive episode at 2 years of age. She took anticonvulsants such as diphenylhydantoin (DPH) and Phenobarbital (PB) thereafter. Although their plasma concentration was within the effective level, she developed GTC frequently from 15 years of age. She then began to take VPA (30mg/kg/day) in addition to DPH and PB, resulting in marked reduction of GTC frequency. Regular check-up revealed hyperammonemia after 5 years and 2 months of VPA administration. Plasma ammonium concentration was 233.6 μg/dl which was approximately three times higher than the controls (Normal range: 24.0-79.0μg/dl). No family history suggesting congenital metabolic disorders was obtained.Plasma VPA and hyperammonemia were not detected one and two weeks after the cessation of VPA, respectively. Amino acid analysis showed numerous imbalance: hyperglycinemia, hyperglutaminemia, low concentration of glutamate family (glutamate, proline, hydroxyproline) and aspartate family (aspartate, lysine, homoserine, methionine, threonine, isoleucine). The plasma concentration of lactic acid was low and that of pyruvic acid was high. Those imbalance of amino acid and organic acid became within normal limits 3 months after the cessation of VPA.In another patient S. M. (a 12-year-old boy, severe mental retardation with GTC) receiving VPA, almost the same results were obtained. It is, however, not yet ascertained whether or not these imbalance are universally detected in all patients receiving VPA.There have been no reports describing the long-term effects of metabolic imbalance induced by VPA, and these might be related to many side effects of VPA. Although VPA is a highly effecttve anticonvulsant against various types of seizures, we conclude that it is necessary to evaluate the metabolic status regularly in those patients receiving VPA.
- 一般社団法人 国立医療学会の論文
一般社団法人 国立医療学会 | 論文
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