Crigler-Najjar Syndrome

Excerpt

Crigler-Najjar syndrome is a rare autosomal recessive disorder causing hyperbilirubinemia in newborns. Bilirubin metabolism involves the uptake of bilirubin from circulation, intracellular storage, conjugation with glucuronic acid, and excretion into bile. Abnormalities in any of these processes lead to hyperbilirubinemia. Crigler-Najjar syndrome is characterized by the absence or decreased activity of UDP-glucuronosyltransferase (UGT), an enzyme required for glucuronidation of unconjugated bilirubin in the liver. This deficiency is a significant cause of congenital nonhemolytic jaundice.

The syndrome is classified into 2 types based on the level of UGT activity:

1. Type 1: Characterized by severe symptoms due to minimal or a complete absence of enzyme activity, individuals with Crigler-Najjar syndrome type 1 (CN1) experience life-threatening and severe jaundice, requiring regular phototherapy for treatment. Patients with this form of the disease are at very high risk of developing neurological complications, including permanent damage such as kernicterus. The only cure for CN1 syndrome is a liver transplant.

1. Type 2: This form of Crigler-Najjar syndrome is characterized by milder symptoms resulting from reduced enzyme activity. Individuals with Crigler-Najjar syndrome type 2 (CN2) experience intermittent jaundice triggered by stress and typically manage the condition through conservative measures. Permanent neurological damage is rare in CN2, and the need for a liver transplant is infrequent.