Crigler-Najjar syndrome is caused by a disorder in the metabolism of bilirubin, the chemical that causes jaundice. It causes severe, permanent brain damage. Crigler-Najjar syndrome is a rare form of congenital non-haemolytic hyperbilirubinaemia.
Crigler-Najjar syndrome is inherited as a recessive condition. This means that a child must receive two abnormal copies of the gene, one from each parent. The parents who have one abnormal copy of the gene are said to be carriers, and are not affected. Crigler-Najjar syndrome is caused by an abnormal gene which fails to produce a functional enzyme (bilirubin glucuronyltransferase) capable of converting bilirubin into a water-soluble and therefore, easily excreted form. As a result, bilirubin can build up in the body, which 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 normal enzyme activity of a normal adult. Type I Crigler-Najjar syndrome is characterised by a total deficiency of hepatic glucuronyl transferase. It is inherited as an autosomal recessive. Conjugated bilirubin is absent from the serum. The majority die with kernicterus in the first year of life. Phototherapy can reduce the serum bilirubin by 50% and may be performed at home. ype II Crigler-Najjar syndrome is characterised by a partial deficiency of glucuronyl transferase. It is inherited as an autosomal dominant. Patients given phenobarbital often survive into adult life. Phototherapy may be used to lower the serum bilirubin level.
Infants who inherit the trait from both parents (this is called 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 which 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. Children with Crigler-Najjar syndrome present soon after birth with severe jaundice, a yellow colouring to the skin.
A build up of bilirubin, the chemical responsible for jaundice, can cause damage to the brain, and this may be apparent in the period soon after birth. This severe, prolonged jaundice is usually the feature that leads to the diagnosis.
Phototherapy is needed on an ongoing basis throughout life. In infants this is done using bilirubin lights (bili or 'blue' lights). Phototherapy becomes less successful after 4 years because thickened skin blocks the light. Liver transplantation has been used successfully for some people with type I disease.