Enzyme

Typical clinical features

Ornithine transcarbamylase

Severe encephalopathy with onset at between 24 and 48 h of life in male homozygotes. Mild recurrent encephalopathy after protein-rich meals in female heterozygotes. Mild liver dysfunction [1, 3]

Carbamyl phosphate synthetase

Early onset: in the first month of life, lethargy, coma

Late onset: coma induced by pregnancy or valproic acid, rarely focal strokes [1, 2]

Citrullinemia type I

Argininosuccinic acid synthetase

Pediatric onset: vomiting, failure to thrive, hepatomegaly, developmental delay, protein avoidance, lethargy.

Adult onset: insomnia, sleep reversal, nocturnal sweats and terrors, recurrent vomiting (especially at night), diarrhea, tremors, episodes of confusion after meals, lethargy, convulsions, delusions and hallucinations, and brief episodes of coma [1, 2]

Argininosuccinate lyase

Vomiting, feeding lethargy in the first few days of life, subsequently developmental delays and infection-induced episodes of hyperammonemia. Mild liver fibrosis [1, 2]

Arginase

Onset in childhood, developmental delay, seizures, lethargy after high-protein meals [1, 2]