Overview

This section provides a brief overview of Crigler Najjar Syndrome.

A1. WHAT IS CRIGLER NAJJAR SYNDROME?

Crigler Najjar Syndrome (CNS) is a rare, but serious condition that causes persistent high levels of bilirubin in the blood and tissue. This is technically called hyperbilirubinemia. The skin and other tissues are a yellow/orange colour, referred to as Jaundice. Uncontrolled hyperbilirubinemia can cause brain damage (kernicterus).

A2. HOW COMMON IS CNS?

CNS occurs worldwide, but is rare. It is estimated that there are about 50 to 100 cases in the USA and perhaps a similar number in Europe. There are about 5 cases in Australia. In some communities, the condition is relatively more common. Examples include the Netherlands and the Amish and Mennonite communities in the USA. Until phototherapy treatment was developed in the 1970s most people with CNS died in infancy. For this reason there are, at present, relatively few people with CNS over 30.

Because of the rarity of the condition good quality information is less readily available than is desirable. This website seeks to make a contribution to rectifying this information gap.

A3. WHAT ARE THE SYMPTOMS?

Because of the high blood and skin bilirubin levels, CNS people have a persistent orange/yellow skin colour and the whites of the eyes are usually yellow. Untreated, CNS can cause much more serious symptoms.

A4. HOW SERIOUS IS THE CONDITION?

Very serious brain damage (kernicterus) may result from high blood bilirubin levels. This can happen within the first month of life, unless treatment is provided. Even with good treatment and management of the condition, other illnesses and some drugs can cause brain damage at lower blood bilirubin levels. For most CNS people, treatment and management have very significant, but not necessarily debilitating, impacts on lifestyle.

A5. HOW IS CNS DIAGNOSED?

Many term babies are jaundiced in the first few days of life. A high proportion are put under blue lights until their livers start to function normally, usually within 10 days of birth. There are a number of conditions that may make the jaundice continue for perhaps a month before bilirubin levels return to normal.

Unless CNS is suspected because of family history, these other causes need to be ruled out before CNS is diagnosed. The diagnosis can be confirmed by either bile analysis or by genetic testing. Neither is a routine test and each requires specialist resources.

Although the diagnosis may take some weeks, during this time it is absolutely vital to take action to control blood bilirubin below dangerous levels. (See Questions C3 and C11). The American Academy of Pediatrics has recently published a clinical practice guideline covering this period. (See Question B2: Reference 3)

A6. WHAT CAUSES CNS?

Everyone has two copies of a gene that produces the liver enzyme (“glucuronyl transferase”) essential for the normal method of removing bilirubin from the blood. There is a range of possible defects that can occur on this gene. Defects on both copies of this gene can cause the normal method of removal of bilirubin to fail, either partially or totally. As a result, blood bilirubin levels increase at rates related to the level of active enzyme present.

A7. WHO GETS AFFECTED BY CNS?

Babies born with the more serious genetic defects become very seriously and persistently jaundiced in the first month of life. Where the defect is less serious and there is some activity of the enzyme, the condition may go undiagnosed for some time.

A8. IS THERE A CURE FOR CNS?

Currently the only known cure is a total or partial liver transplant, a serious surgical operation that is followed by long-term use of drugs that suppress the immune system and leave the person more exposed than normal to a range of other illnesses.

A9. CAN CNS BE TREATED?

Yes. Some of the less serious genetic defects reduce the amount of enzyme produced rather than produce an inactive enzyme. In these cases phenobarbital and some other drugs may, in some circumstances, be able to stimulate the production of the enzyme enough to control blood bilirubin to a level below that which could cause brain damage.

In many cases the only method of controlling blood bilirubin levels is the use of intensive blue light phototherapy. Depending on the effectiveness of the phototherapy equipment and the seriousness of the defect, this may require many hours of treatment at night or during the day.

A10. WHAT IS MEANT BY CRIGLER NAJJAR TYPE 1 AND TYPE 2?

In the early years of the study of CNS it was found that, for some CNS people, controlled doses of the drug phenobarbital reduced blood bilirubin to some extent. When his happened the condition was catagorised as Type 2 and regarded as less serious. Failure to respond to phenobarbital was categorised as Type 1.

This distinction continues to be used, but the categorisation is somewhat simplistic. Some CNS people who do not respond to phenobarbital nevertheless have some low level of natural enzyme activity and some low level capacity to reduce bilirubin. These people can normally be held safe with lesser levels of phototherapy treatment than Type 1 CNS people.

In general, Type 1 cases are the most serious. Type 2 cases may be less serious, but nevertheless require careful monitoring, treatment and management.