Carglumic Acid Treatment of a Patient with Recurrent Valproic Acid-induced Hyperammonemia: A Rare Case Report

Abstract

Valproic acid, first manufactured as an anticonvulsant, is commonly used to treat both neurological and psychiatric conditions. A rare and deadly side effect of this medication is hyperammonemia, presenting as lethargy, confusion, seizure, and, ultimately, coma. In rare circumstances, hyperammonemia can be recurrent and devastating, especially in patients with an underlying N-acetyl glutamate synthase (NAGS) deficiency, as the valproic acid can enhance this enzyme deficiency and inhibit the conversion of ammonia into urea in the liver. For these subtypes of patients, the United States Food and Drug Administration (US FDA) has recently approved carglumic acid, a medication that can act as a scavenger by effectively increasing the levels of NAGS, ultimately enhancing the conversion of ammonia to urea. In our case report, we have mentioned a patient with treatment-resistant bipolar disorder, who presented with elevated ammonia levels secondary to valproic acid treatment. Valproic acid was the only drug that was effective in his case, so we initiated therapy to reduce his elevated ammonia levels. After a thorough evaluation, we found the patient had a genetic NAGS deficiency. Carglumic acid was initiated and proved efficacious in our patient.

Use of carglumic acid in valproate‐induced hyperammonemia: 25 pediatric cases

“…Recurrences were common in patients who maintained VPA treatment (five out of eight patients, 62%). Our results suggest that CA could be an option to maintain normal ammonemia in patients with VPA‐induced hyperammonemia for whom stopping VPA is not feasible, as proposed by other authors 28 . Moreover, long‐term treatment with CA has been suggested to be effective and well tolerated in patients with organic acidurias 29,30 …”

“…Our results suggest that CA could be an option to maintain normal ammonemia in patients with VPA-induced hyperammonemia for whom stopping VPA is not feasible, as proposed by other authors. 28 Moreover, long-term treatment with CA has been suggested to be effective and well tolerated in patients with organic acidurias. 29,30 Potential side effects of CA include vomiting, diarrhea, stomach pain, fever, or headache and they were not observed, or at least recorded, in our patients.…”

Valproic Acid–Associated Hyperammonemia

“…Manual search of reference lists and gray literature did not identify additional studies. After screening and assessing for eligibility, 240 studies were included with the remaining articles being excluded for meeting the exclusion criteria 6,7,12–245 . Among the excluded 350 articles, 37 were literature reviews, 5 were pharmacokinetically related, 41 were VPA overdose related, and 267 articles were unable to clearly answer our objectives listed.…”

Two Siblings With Valproate-Related Hyperammonemia and Novel Mutations in Glutamine Synthetase (GLUL) Treated With Carglumic Acid

“…For example, a case of VPA-induced hyperammonemia, with failed carnitine but successful carglumic acid treatment, is described by Sattar et al (2018). 16…”