Crigler-Najjar Syndrome

Crigler-Najjar syndrome is an inherited disorder of bilirubin metabolism. It is an autosomal recessive disorder, meaning that an individual needs to receive two copies of the defective gene, one from each parent, in order to develop the syndrome. There are less than 50 known cases of Crigler-Najjar syndrome in the United States, and only several hundred worldwide have been reported. The real prevalence of the syndrome is unknown. It affects both males and females of all ethnic backgrounds.

Symptoms
Crigler-Najjar syndrome has two distinct forms. Both involve deficiency of an enzyme called UGT.

• Type 1 is associated with the production of little or no UGT, which causes very high levels of bilirubin to build up in the body. Jaundice, the yellowish appearance of the skin and eyes due to the excess bilirubin, is present at or soon after birth.
• Type 2 is associated with low UGT activity, and therefore lower levels of bilirubin in the body than in type 1. Jaundice may not appear until later in infancy or childhood.

If Crigler-Najjar syndrome type 1 is not identified and treated at birth, the excess bilirubin may cause brain damage, known as bilirubin encephalopathy or kernicterus. Symptoms of kernicterus are low muscle tone (hypotonia), deafness, and lethargy; death or permanent brain damage may result.

Diagnosis
High levels of bilirubin in the blood along with normal liver function tests is characteristic of Crigler-Najjar syndrome. Infants with Type 1 will be jaundiced and have bilirubin levels of 17-50 mg/dL. Crigler-Najjar syndrome Type 2 may be suspected in infants and children who are jaundiced and have bilirubin levels of 6-22 mg/dL.

Treatment
Prompt treatment of excess bilirubin in infants with Crigler-Najjar syndrome type 1 is necessary in order to prevent kernicterus. Treatment usually involves plasma exchange transfusion. This removes the bilirubin-saturated protein from the blood. Long-term phototherapy (bili lights) is started as well. The phototherapy helps break down the bilirubin into a form which can be excreted in the urine. Oral calcium phosphate may also be given. Because children with type 1 have little or no UGT, they must continue to receive daily phototherapy in order to survive.

Children with Crigler-Najjar syndrome type 2 may not require any treatment or may have their excess bilirubin managed with phenobarbital, which causes UGT to be more active.

Information for this article was taken from:
- The Crigler-Najjar Association
- Pigazzi, A., & Ravalli, S. (2002). Crigler-Najjar syndrome. eMedicine, accessed at http://www.emedicine.com/med/topic476.htm