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Published Online, 15 November 2005, www.theannals.com, DOI 10.1345/aph.1G167.
 The Annals of Pharmacotherapy: Vol. 39, No. 12, pp. 2119-2122. DOI 10.1345/aph.1G167
© 2005 Harvey Whitney Books Company.
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Acute Hyperammonemic Coma with Chronic Valproic Acid Therapy

Miroslav Cuturic, MD1, and Ruth K Abramson, PhD2

1 Assistant Professor, Division of Neurology, Department of Neuropsychiatry and Behavioral Science, School of Medicine, University of South Carolina, Columbia, SC
2 Professor And Chief Of Psychiatric Ge-Netics, Hall Institute Of Psychiatry, Department Of Neuropsychiatry And Behavioral Science, School Of Medicine, University Of South Carolina

Reprints: Dr. Cuturic, Department of Neuropsychiatry and Behavioral Science, University of South Carolina, 15 Medical Park, Ste. 103, Columbia, SC 29203-6894, fax 803/434-3792, mirocuturic{at}yahoo.com

OBJECTIVE: To report a case of dose-related hyperammonemic coma without liver failure in a patient receiving chronic valproate therapy.

CASE SUMMARY: A 56-year-old woman with poorly controlled epilepsy, receiving valproate at subtherapeutic levels for 6 years, developed a life-threatening hyperammonemic coma following a moderate dosage increase.

DISCUSSION: Hyperammonemic coma without associated liver failure is an extremely rare complication of valproate therapy, described primarily in patients with inborn errors of metabolism and occurring idiosyncratically during initial stages of therapy. In our case, family history was suggestive of an X-linked disorder, raising the possibility that our patient may have been an asymptomatic carrier of a urea cycle enzyme deficiency unmasked by valproate therapy. To our knowledge, as of October 24, 2005, only one prior case of hyperammonemic coma in the context of chronic valproate monotherapy has been described. Application of the Naranjo probability scale score suggests that a causal relationship between valproic acid and hyperammonemic coma was probable.

CONCLUSIONS: The widespread use of valproic acid emphasizes the need to maintain a high degree of suspicion with respect to this rare but potentially fatal adverse effect at all times, regardless of therapy duration.

Key Words: hyperammonemia, hyperglycerolemia, valproic acid

Published Online, November 15, 2005. www.theannals.com, DOI 10.1345/aph.1G167




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