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.