The urea cycle disorders (UCDs) are a group of inborn errors of metabolism that are associated with defective ureagenesis. The urea cycle comprises of N-Acetyl Glutamate Synthase, a cofactor-synthesizing enzyme, five catalytic enzymes, i.e., carbamoyl-phosphate synthase 1 (CPS1), ornithine transcarbamylase (OTC), argininosuccinate synthase (ASS1), argininosuccinate lyase (ASL), arginase (ARG1), and amino acid two transporters, citrin and ORNT1 that facilitate conversion of nitrogen from ammonia and aspartate into urea. With deficiency of any of these components, there is a block in ureagenesis that results in accumulation of ammonia and hyperammonemic encephalopathy, which can be associated with high mortality and morbidity.
All UCDs are inherited as autosomal-recessive traits, except for OTC deficiency, which is X-linked. With the exception of ARG1 deficiency, infants with a complete deficiency of any of the other urea cycle enzymes commonly present in the newborn period with hyperammonemic coma. The universal newborn screening in all 50 states has facilitated earlier diagnosis of the UCDs. The availability of nutritional supplements, formulae, nitrogen-scavenging medications, and dialysis have improved the outcome for patients; however it is often challenging to manage those with severe forms of UCDs.