Classic Citrullinemia

Citrullinemia type I (CTLN1) is a urea cycle disorder caused by biallelic pathogenic variants in the ASS1 gene. Compared to proximal urea cycle defects, hyperammonemia could be less severe and less common. Other biochemical abnormalities include elevated glutamine, elevated citrulline, extremely low argininosuccinic acid, low or normal plasma arginine levels in the amino acid profile, and elevated urinary orotic acid. Early-onset disease phenotype presents with severe and life-threatening hyperammonemic events with acute encephalopathy during the early neonatal period, while the late-onset disease phenotype presents with variable neuromuscular/neuropsychiatric manifestations.