Health Encyclopedia

Crigler-Najjar syndrome

Definition

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.

Alternative Names

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

Causes, incidence, and risk factors

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.

Symptoms

A family history of Crigler-Najjar syndrome
Yellow skin (jaundice) and yellow color of the whites of the eyes (icterus), which begin on the 2nd or 3rd day of life and progressively worsens
Jaundice that persists beyond 2 weeks without an obvious cause
Confusion and changes in thinking (resulting from brain toxicity of bilirubin)

Signs and tests

Tests used to evaluate the liver function include:

Unconjugated (unbound) bilirubin in blood (would be highly elevated)
Total bilirubin level (would be high)
Conjugated (bound) bilirubin (would be low to absent)
Liver biopsy, enzyme assay for low or absent Glucuronyl transferase activity
A family history of Crigler-Najjar syndrome

Treatment

Phototherapy (light treatment) 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.

Expectations (prognosis)

Affected individuals who reach adulthood will develop kernicterus despite ongoing treatment. The life expectancy for type I disease has been extended from death in childhood to people now living to at least age 30.

Complications

Possible complications include:

Kernicterus
Chronic yellow skin/eyes

Calling your health care provider

Seek genetic counseling if you are planning to have children and have a family history of Crigler-Najjar.

Call your health care provider if you or your newborn infant has prolonged jaundice.

Prevention

Genetic counseling is recommended for prospective parents with a family history of Crigler-Najjar syndrome. People who carry the gene can be recognized by blood testing.

Review Date:8/11/2006
Reviewed By:Brian Kirmse, MD, Mount Sinai School of Medicine, Department of Human Genetics, New York, NY. Review provided by VeriMed Healthcare Network.

ADAM Quality A.D.A.M., Inc. is accredited by URAC, also known as the American Accreditation HealthCare Commission (www.urac.org). URAC's accreditation program is the first of its kind, requiring compliance with 53 standards of quality and accountability, verified by independent audit. A.D.A.M. is among the first to achieve this important distinction for online health information and services. Learn more about A.D.A.M.'s editorial process. A.D.A.M. is also a founding member of Hi-Ethics (www.hiethics.com) and subscribes to the principles of the Health on the Net Foundation (www.hon.ch).

The Agency for Health Care Administration (Agency) and this website do not claim the information on, or referred to by, this site is error free. This site may include links to websites of other government agencies or private groups. Our Agency and this website do not control such sites and are not responsible for their content. Reference to or links to any other group, product, service, or information does not mean our Agency or this website approves of that group, product, service, or information.

Additionally, while health information provided through this website may be a valuable resource for the public, it is not designed to offer medical advice. Talk with your doctor about medical care questions you may have.