Objective:

Background:

OTC deficiency is a rare x-linked disorder that results in neurotoxic hyperammonemia. Males typically present at birth with severe symptoms, while females present later in life with mild symptoms provoked by stressors/infections. Seizures have been reported during the acute hyperammonemia stage.  

Design/Methods:

A 9-year-old girl presented with a 3-day history of encephalopathy which was preceded by a respiratory infection and UTI. Her initial exam was significant for lethargy, disorientation, and disconjugate gaze. Initial labs were negative aside from hyperammonemia (259, normal 11–51). EEG showed mild encephalopathy. MRI brain on day one was essentially normal. Inborn error of metabolism labs were ordered, and IV infusions of sodium benzoate-sodium phenylacetate and arginine were started for hyperammonemia. With this treatment, she had rapid clinical improvement, and her ammonia normalized by day three. Two days later, she had a first-time focal seizure. Urgent MRI brain showed new restricted diffusion in the calcarine sulcus. Within an hour, she progressed to super refractory convulsive status epilepticus requiring a pentobarbital coma. Her ammonia remained normal during this time. On day 6, a rapid whole exome sequencing confirmed OTC deficiency. On day 9, repeat MRI showed restricted diffusion of bilateral basal ganglia and claustrum. By day 10, her ammonia rose again and required prolonged CRRT for stabilization. She ultimately had a prolonged, complicated hospital stay and remained severely encephalopathic post-extubation.  

Results:

N/A

Conclusions:

Risk of seizures and status epilepticus is not exclusive to the acute hyperammonemia stage, as previously reported. Delayed MRI findings and neurologic effects of hyperammonemia, such as super refractory status epilepticus, may present days after ammonia has normalized. OTC deficiency in females is not always mild and can have severe, life-threatening complications with prolonged hospitalization.