Valproate Toxicity and Ornithine Carbamoyltransferase Deficiency

Kay, JonathanD.S.; Hilton‐Jones, David; Hyman, Nigel

doi:10.1016/s0140-6736(86)92714-5

Cited by 57 publications

(19 citation statements)

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“…This encephalopathy is most common after initiation of treatment with VPA, but also after associating a second antiepileptic agent [7][8][9]. A few cases of VPAinduced hyperammonemic encephalopathy have been described in patients with inborn errors of the hepatic ammonia metabolism (urea cycle defects) [10,11].…”

Section: Discussionmentioning

confidence: 99%

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Valproate-Induced Hyperammonemic Encephalopathy: Imaging Findings on Diffusion-Weighted MRI

et al. 2004

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Section: Discussionmentioning

confidence: 99%

“…First, the renal production of ammonia is increased by means of an enhanced glutaminase activity. Second, there is a reduction of the hepatic fatty acid metabolism by a reduced availability of carnitine and an inhibition of carbamoylphosphate synthetase [9,11,12]. Both mechanisms cause hyperammonemia.…”

Section: Discussionmentioning

confidence: 99%

Valproate-Induced Hyperammonemic Encephalopathy: Imaging Findings on Diffusion-Weighted MRI

et al. 2004

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“…The decreased blood glutamine level observed in our study might support the hypothesis that ordinary short-term treatment with CFTM-PI induces ATP and acetyl-CoA insufficiency because of carnitine deficiency, CoA sequestration or a combination of both. Kay et al(1986) and Hjelm et al (1986) have reported cases in which occult metabolic disorders were revealed during the administration of VPA. In other studies, L-carnitine supplementation was tried for normalization of carnitine deficiency in VPA-treated patients (Ohtani et al 1982;Sakemi et al 1992).…”

Section: Discussionmentioning

confidence: 99%

Alteration of Ammonia and Carnitine Levels in Short-Term Treatment with Pivalic Acid-Containing Prodrug.

Ito

Sugiyama

Kobayashi

et al. 1995

Tohoku J. Exp. Med.

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We investigated the influence on mitochondrial functions in carnitine deficiency caused by short-term treatment of cefterampivoxil (CFTM-PI) which is one of pivaloyloxymethyl-esterified antibiotics in adult volunteers and diseased children. Administration of CFTM-PI caused hypocarnitinemia in all cases, and we observed a significant elevation of blood ammonia levels compared with those after its withdrawal in diseased children. A significant negative correlation was found between the levels of serum free carnitine and blood ammonia, and a positive correlation was observed between serum carnitine and blood glutamine levels in all adult samples and samples during administration in diseased children. Our data suggest that these antibiotic medications affect the mitochondrial function even in a short-term treatment and that L-carnitine supplementation would be necessary for patients treated with CFTM-PI. carnitine deficiency; pivalic acid; hyperammonemia Carnitine, a cofactor for mitochondrial /l-oxidation of long-chain fatty acids, is essential for energy production and enhances the excretion of accumulated acyl-CoA to regulate the intramitochondrial CoA/acyl-CoA ratio. The systemic carnitine deficiency noted in various disorders can cause hypoketotic hypoglycemia, cardiomyopathy and Reye-like syndrome because functions of carnitine are insufficient.Some oral antibiotics in general use are esterified with pivaloyloxymethyl moiety in order to increase the intestinal absorption rate. This group of antibi-

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“…It can also be used to treat bipolar depression, psychoaffective disorders, neuropathic pain and migraines (Löscher, 1999). Valproic acid-induced encephalopathy (VAE) is a rare complication and can result in death if not diagnosed early (Kay et al, 1986). VAE can be accompanied by deterioration of consciousness, focal neurological findings, ataxia, cognitive slowness, vomiting and seizures.…”

Section: Introductionmentioning

confidence: 99%