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Definition
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 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 kernicterus (bilirubin encephalopathy) due to bilirubin toxicity.
Clinical manifestation
Crigler-Najjar syndrome is manifested by severe, persistent jaundice, a condition in which
the skin and the whites of the eyes become yellow. This is due to excessive plasmatic levels of bilirubin (> 20 mg/dL in Crigler-Najjar type I patients). Whether untreated severe jaundice may result in brain damage (kernicterus) with possible permanent effects. As results of brain damage clinical manifestations of kernicterus include hypotonia, lethargy, deafness, oculomotor palsy.
Genetics
The disease is inherited as an autosomal recessive trait, meaning that the gene involved is not on one of the sex chromosomes; it also means that in order for a person to have the disorder the genetic change must be present in both copies of the gene, one inherited from the mother and one from the father. In other words, parents of a Crigler-Najjar patient have a copy of the UGT1A1 gene mutated (they are "carriers" of the disease). This do not have a significant effect on the bilirubin levels, since one copy of the gene is functional. In Crigler-Najjar patients both of the copies of the gene are mutated. Two carriers have a 25% chance with each pregnancy of having a child affected by the disorder; a 50% chance of having an unaffected child who is a carrier of the disorder and a 25% chance that the child will not have the disorder and will not be a carrier (see also Crigler-Najjar and pregnancy page).
Several gene alterations have been discovered in Crigler-Najjar syndrome patients, leading to reduced or absent UGT1A1 activity causing hyperbilirubinemia. Full-length cDNA for human UGT1A1 has been cloned and sequenced.
Crigler-Najjar syndrome is very rare, real incidence is unknown (approx. less than 1 case per 1,000,000 births).
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Home |
Definition |
Treatment |
Genetics |
The Gunn Rat |
Bilirubin Toxicity |
Crigler-Najjar and pregnancy |
Bilirubin Level & Drugs |
Phototherapy |
Crigler Najjar Registry |
Crigler Najjar type II |
Links |
News |
Updates
 
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