Crigler-Najjar syndrome

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Liver anatomy

Crigler-Najjar syndrome is an inherited disorder in which bilirubin (a substance made by the liver) cannot be changed into its water-soluble form, bilirubin glucuronide. This causes jaundice (yellow discoloration of skin and eyes) and organ malfunctions.

Glucuronyl transferase deficiency (type I Crigler-Najjar); Arias syndrome (type II Crigler-Najjar)

Crigler-Najjar syndrome is caused by an abnormal gene. The gene fails to make a working enzyme (bilirubin glucuronyltransferase). This enzyme, in its normal (working ) form, is capable of converting bilirubin into a water-soluble (and therefore easily excreted) form. As a result, bilirubin can build up in the body, and can damage the brain and other organs.

The syndrome is inherited as an autosomal recessive trait. This means that the child must get the defective gene from both parents to develop the severe form of the condition. Parents who are carriers (with just one defective gene) have about half the enzyme activity of a normal adult.

Infants who inherit the trait from both parents (this is called being homozygous for the abnormal gene) develop severe jaundice (hyperbilirubinemia) beginning a few days after birth. If these infants are not treated, they may develop kernicterus, which is bilirubin toxicity of the brain and can be fatal.

In such infants, the jaundice will persist into adult life and may require daily treatment. The constantly elevated levels of bilirubin may eventually produce an adult form of kernicterus despite treatment. If left untreated, this severe infant-onset form of the disease will lead to death in childhood.

Milder forms of the disease (type II) are not associated with severe toxicity, liver damage, or changes in thinking during childhood. Affected individuals still have jaundice, but they have fewer symptoms and less organ damage.

Review Date: 08/11/2006
Reviewed By: Brian Kirmse, MD, Mount Sinai School of Medicine, Department of Human Genetics, New York, NY. Review provided by VeriMed Healthcare Network.