OTC main chain variants cause OTC deficiency

OTC deficiency (OTCD) is an X-linked metabolic disorder of the urea cycle that leads to hyperammonemia, neurological complications and in the most pronounced cases, death (reviewed in Couchet et al, 2021; Schmitt Ribas et al, 2022). OTCD arises from mutations distributed across the functional domains of the protein and can present as a severe neonatal form (often affecting residues involved in catalysis or substrate binding and resulting in severely compromised enzymatic activity) or as later onset, clinically milder forms that affect surface or domain-interface residues and that retain partial enzymatic function (reviewed in Couchet et al, 2021; Schmitt Ribas et al, 2022).