Carbamoyl phosphate synthetase I deficiency

Carbamoyl phosphate synthetase I deficiency, or CPS I deficiency, is an autosomal recessive metabolic disorder in which the liver lacks the enzyme that starts the urea cycle, so ammonia accumulates in the blood. Ammonia is toxic at high levels and the nervous system is especially sensitive to it. In the severe form the illness shows in the first days of life, when an infant may be lethargic, unwilling to feed, and have poorly controlled breathing or body temperature, and some go on to seizures, coma, developmental delay and intellectual disability. Milder cases may not appear until later in life. Mutations in the CPS1 gene cause it, placing it among the urea cycle disorders. Management begins with reducing protein intake, maintaining energy intake and giving intravenous glucose, with sodium benzoate, sodium phenylacetate and arginine to clear ammonia, and hemodialysis when levels are extremely high. In 2025 a newborn with a severe form received a bespoke base-editing therapy reported in the New England Journal of Medicine.