Crigler-Najjar syndrome is a genetic disease characterized by a persistent unconjugated hyperbilirubinemia (elevated bilirubin levels).
Bilirubin is the waste product of the breakdown of hemoglobin occurring during the normal turnover of red blood cells. Bilirubin is not soluble in water and before excretion in the bile must be associated with a substance called glucuronid acid. This process takes place in the liver thanks to the bilirubin-uridine diphosphoglucuronate glucuronosyltransferase (B-UDPGT), also known as UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme. In Crigler-Najjar patients the enzyme is either inactive (type I) or severely reduced (type II). Therefore, bilirubin cannot be excreted into the bile and remains in the blood. The high plasma level of unconjugated bilirubin leads to jaundice and may lead to bilirubin-induced neurologic damage (kernicterus, bilirubin encephalopathy) due to bilirubin toxicity.
