Citrin deficiency is an inborn error of metabolism that appears to affect both the urea cycle and energy generation. Worldwide, citrin deficiency is likely one of the commonest inborn errors of metabolism, 60,000–80,000 individuals are estimated to have citrin deficiency in China alone. Children typically present with an abnormal newborn screen or neonatal intrahepatic cholestasis with citrin deficiency (NICCD). Adults typically present clinically with neuropsychiatric symptoms, hepatic dysfunction and hyperammonemia. As plasma amino acids typically show an elevated citrulline at the time of crisis, this presentation is known as citrullinemia type II (CTLN2). Without therapy, cases may progress to liver failure. Individuals may also suffer recurrent pancreatitis. In contrast to other urea cycle defects, the treatment for citrin deficiency requires a high protein, low carbohydrate diet. Acute hyperammonemia responds to arginine therapy. Sodium pyruvate has been reported to provide benefit. In addition many cases will require restriction of galactose. Liver transplant fully corrects the CTLN2 phenotype.
Therapeutic approaches for patients with adult-onset type II citrullinemia (CTLN2): effectiveness of treatment with low-carbohydrate diet and sodium pyruvate