Crigler-Najjar syndrome (CNS), named for the two physicians who first described the condition in 1952, John Crigler and Victor Najjar, is a rare, life-threatening inherited condition that affects the liver. CNS is characterized by a high level of a toxic substance called bilirubin in the blood (hyperbilirubinemia).
Bilirubin is produced during the normal process of breaking down of red blood cells. In order to be removed from the body, bilirubin goes through a chemical reaction in the liver where an enzyme called uridine diphosphate glucuronosyl transferase (UGT) converts the toxic form of bilirubin into a soluble form (a process known as “bilirubin conjugation”) that can be eliminated from the body through the bile and into the intestines. See the graphic titled Normal State below.
In CNS, the UGT enzyme is either completely inactive (CNS type I) or severely reduced (CNS type II). In both types, bilirubin is not broken down properly and cannot be excreted into the bile. High levels of unconjugated bilirubin accumulate in the blood and this leads to jaundice and may travel to the brain and result in a severe form of brain damage called kernicterus (more on this below). CNS type I, in which the body produces no, or very little, UGT is much more severe and can result in death in early childhood. CNS type II, in which the body produces moderate but reduced amounts of UGT, is less severe, less likely to cause kernicterus, and patients may respond to some medications. See the graphic titled Abnormal State below.