Unusual cause of hyperammonemia in two cases with short-term and long-term valproate therapy successfully treated by single dose carglumic acid
A 15-year-old male with a 1-month history of epilepsy, headache, and hemiparesis was admitted to the pediatric intensive care unit with altered mental status. The child was managed conservatively along with intravenous antibiotics and was started on intravenous valproate at a dosage of 33 mg/kg and levetiracetam 44 mg/kg was added for breakthrough seizures. He was intubated because of impaired consciousness with increasing confusion and lethargy and increased seizure frequency. The alteration of consciousness was subsequent to the administration of valproate and not due to a progression of the disease. A metabolic encephalopathy was suspected. Laboratory investigations revealed hyperammonemia 283 μg/dl 6 days after initiating valproic acid (VPA) and no signs of hepatotoxicity. There was no family history of any genetic-metabolic disorder. The valproate was ceased and a single dose of carglumic acid 100 mg/kg per day was administered through a nasogastric tube, followed by a rapid improvement in the patient's mental state and a return of the ammonia level to the normal range (50 μg/dl). Blood ammonia remained normal thereafter.