Crigler-Najjar syndrome

Definition

Crigler-Najjar syndrome is a very rare inherited disorder in which bilirubin (a substance made by the liver) cannot be broken down.

Alternative Names

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

Causes, incidence, and risk factors

Crigler-Najjar syndrome occurs when the enzyme that normally converts bilirubin into a form that can easily be removed from the body does not work correctly. Without this enzyme, bilirubin can build up in the body and lead to jaundice (yellow discoloration of skin and eyes) and damage to the brain, muscles, and nerves.

Crigler-Najjar (type 1) is the early-onset form of the disease. Arias syndrome (type 2) is a later-onset condition.

The syndrome runs in families (inherited). A child must receive a copy of 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.

Symptoms

• Confusion and changes in thinking
• Yellow skin (jaundice) and yellow in the whites of the eyes (icterus), which begin a few days after birth and get worse over time

Signs and tests

Tests used to evaluate liver function include:

• Conjugated (bound) bilirubin
• Liver biopsy, enzyme assay
• Total bilirubin level
• Unconjugated (unbound) bilirubin in blood

Treatment

Light treatment (phototherapy) is needed on a regular basis throughout life. In infants this is done using bilirubin lights (bili or 'blue' lights). Phototherapy becomes less successful after age 4, because thickened skin blocks the light.

Liver transplantation has been used successfully in some people with type 1 disease.

Blood transfusions may help control the amount of bilirubin in blood plasma. Calcium compounds are sometimes used to bind with and remove bilirubin in the gut.

The drug phenobarbitol is sometimes used to treat Arias syndrome (type 2).

Support Groups

Expectations (prognosis)

Milder forms of the disease (type 2) do not cause severe toxicity, liver damage, or changes in thinking during childhood. People affected still have jaundice, but they have fewer symptoms and less organ damage.

Infants with the severe form of the disease (type 1) may continue to have jaundice into adulthood, and may need daily treatment. If left untreated, this severe form of the disease will lead to death in childhood.

People with this condition who reach adulthood will develop brain damage due to jaundice (kernicterus), even with regular treatment. The life expectancy for type 1 disease is 30 years.

Complications

Possible complications include:

• A form of brain damage caused by jaundice (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 jaundice that does not go away.

Prevention

Genetic counseling is recommended for prospective parents with a family history of Crigler-Najjar syndrome. Blood testing can identify people who carry the gene.

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References

Carey RG, Balistreri WF. Metabolic Diseases of the Liver. In: Kliegman RM, Behrman RE, Jenson HB, Stanton BF, eds. Nelson Textbook of Pediatrics. 18th ed. Philadelphia, Pa: Saunders Elsevier; 2007: chap 354.