Citrullinemia type II

Citrullinemia type II (CTLN2), also known as adult-onset citrullinemia or citrin deficiency (adult form), is a rare inherited metabolic disorder caused by mutations in the SLC25A13 gene, which encodes the mitochondrial aspartate-glutamate carrier protein citrin. This protein plays a critical role in the urea cycle and in the malate-aspartate shuttle within the liver. When citrin is deficient, the liver cannot properly metabolize ammonia, leading to recurrent episodes of hyperammonemia (elevated blood ammonia levels). The disease primarily affects the liver and the central nervous system. Citrullinemia type II typically presents in adulthood, usually between the ages of 20 and 50, although the underlying citrin deficiency is present from birth. Affected individuals may initially present with neonatal intrahepatic cholestasis caused by citrin deficiency (NICCD) in infancy, which usually resolves spontaneously. Later in life, patients develop neuropsychiatric symptoms including confusion, restlessness, disorientation, abnormal behavior, seizures, and coma triggered by hyperammonemic crises. Patients often exhibit a characteristic dietary preference for protein-rich and lipid-rich foods and an aversion to carbohydrate-rich foods and alcohol, which can worsen symptoms. Other features include fatty liver, hepatomegaly, and elevated plasma citrulline and ammonia levels. Some patients may progress to life-threatening encephalopathy. Treatment focuses on managing hyperammonemia through dietary modifications (low-carbohydrate, high-protein and high-fat diet), pharmacological agents such as sodium pyruvate and arginine supplementation, and avoidance of triggers including alcohol, sugary foods, and certain medications. Liver transplantation is the only definitive curative treatment and is recommended for patients with recurrent or severe hyperammonemic episodes. The disease is most prevalent in East Asian populations, particularly in Japan. Early recognition and appropriate dietary management are essential to prevent potentially fatal hyperammonemic crises.

Data sourced from FDA regulatory filings and ClinicalTrials.gov. Updated periodically.

Common questions about Citrullinemia type II