A 17-year-old girl with severe anxiety and depression on Vilazodone with a previous history of psychosis requiring inpatient psychiatric admission, was admitted for 1-week history of worsening neuropsychiatric symptoms including lethargy, vomiting, gait ataxia and agitation.  A serum ammonia level obtained on the second day of admission was elevated at 378 ug/dL (normal range 20-50 ug/dL). Upon taking her history, the patient, her older sister, mother and maternal grandmother consciously avoided protein in their diets. A rapid analysis of blood amino acids by tandem mass spectrometry, showed a characteristic OTC deficiency metabolic profile, including a low normal citrulline, high glutamine and an elevated urinary orotic acid. Mutation analysis revealed a heterozygous pathogenic variant c.422G>A (p.Arg141Gln; AKA R141Q) in the OTC gene consistent with a diagnosis of X-linked OTC deficiency. Our patient was treated with intravenous hydration, hemodialysis, lactulose, intravenous arginine, sodium phenylacetate and sodium benzoate, and a protein-restricted diet. Her mental status and ataxia significantly improved once her ammonia level normalized.  She was restarted on low dose of Vilazodone outpatient and resumed most of her daily activities. She was subsequently discharged on citrulline supplementation, instructions for protein restricted diet and oral glycerol phenylbutyrate with an outpatient evaluation for liver transplant.

Our patient remained undiagnosed until 17 years of age when she presented in acute hyperammonemic crisis. Her prior symptoms of neuropsychiatric disturbances were attributed to anxiety and depression and possible drug side effect.  Undiagnosed OTC deficiency may have been a contributing factor to her psychiatric symptoms.