Definition

What is Crigler-Najjar Syndrome?

Crigler-Najjar syndrome is a severe condition characterized by high levels of a toxic substance called bilirubin in the blood (hyperbilirubinemia). Bilirubin is produced when red blood cells are broken down. This substance is removed from the body only after it undergoes a chemical reaction in the liver, which converts the toxic form of bilirubin (called unconjugated bilirubin) to a nontoxic form called conjugated bilirubin. People with Crigler-Najjar syndrome have a buildup of unconjugated bilirubin in their blood (unconjugated hyperbilirubinemia).

Bilirubin has an orange-yellow tint, and hyperbilirubinemia causes yellowing of the skin and whites of the eyes (jaundice).

How common is Crigler-Najjar Syndrome?

Crigler-Najjar syndrome is rare. It’s estimated to affect fewer than 1 in 1 million newborns worldwide. Please discuss with your doctor for further information.

Symptoms

What are the symptoms of Crigler-Najjar Syndrome?

The common symptoms of Crigler-Najjar Syndrome are:

  • 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
  • Lethargy
  • Poor feeding
  • Vomiting

There may be some symptoms not listed above. If you have any concerns about a symptom, please consult your doctor.

When should I see my doctor?

If your baby has any signs or symptoms listed above or if you have any questions, please consult with your doctor. Everyone’s body acts differently. It is always best to discuss with your doctor what is best for your situation.

Causes

What causes Crigler-Najjar Syndrome?

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.

Type I Crigler-Najjar is the form of the disease that starts early in life. Type II Crigler-Najjar syndrome starts later in life.

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, but DO NOT have symptoms.

Risk factors

What increases my risk for Crigler-Najjar Syndrome?

There are many risk factors for Crigler-Najjar Syndrome, such as:

  • A family history of Crigler-Najjar Syndrome

Diagnosis & treatment

The information provided is not a substitute for any medical advice. ALWAYS consult with your doctor for more information.

How is Crigler-Najjar Syndrome diagnosed?

A diagnosis may be suspected within the first few days of life in infants with persistent jaundice. A diagnosis may be confirmed by a thorough clinical evaluation, characteristic findings, detailed patient history, and specialized testing. For example, in infants with this disorder, blood tests reveal abnormally high levels of unconjugated bilirubin in the absence of increased levels of red blood cell degeneration (hemolysis), as in Rh disease (isoimmunization). In addition, bile analysis reveals no detectable bilirubin glucuronides and urine analysis may demonstrate a lack of bilirubin.

Molecular genetic testing can confirm a diagnosis of Crigler-Najjar syndrome. Molecular genetic testing can detect mutations in the UGT1A1 gene that are known to cause the disorder, but is available only as a diagnostic service at specialized laboratories.

It is important to distinguish Crigler-Najjar syndrome type I and type II. The administration of phenobarbital, a barbiturate, reduces blood bilirubin levels individuals affected with Crigler-Najjar syndrome type II and Gilbert syndrome, but is ineffective for those with Crigler-Najjar syndrome type I. Therefore, failure to respond to this medication is an important indication for differential diagnostic purposes.

How is Crigler-Najjar Syndrome treated?

Treatment is directed toward lowering the level of unconjugated bilirubin in the blood. Early treatment is imperative in Crigler-Najjar syndrome type I to prevent the development of kernicterus during the first few months of life. Because Crigler-Najjar syndrome type II is milder and responds to phenobarbital, treatment is different.

The mainstay of treatment for Crigler-Najjar syndrome type I is aggressive phototherapy. During this procedure, the bare skin is exposed to intense light, while the eyes are shielded. This helps to change the bilirubin molecules in the skin, so that it can be excreted in bile without conjugation. As affected individuals age, the body mass increases and the skin thickens, making phototherapy less effective for preventing kernicterus. For years, fluorescent light has been used, but has drawbacks including exposing patients to ultraviolet radiation. Some doctors recommend using light-emitting diodes (LEDs) technology, which uses blue light. This technology can be adjusted to the specific treatment level needed in an individual and does not expose people to ultraviolet radiation. However, it is not widely available. Exposure of skin to sun light is very effective in reducing blood bilirubin levels.

Infections, episodes of fevers, and other types of illnesses should be treated immediately to reduce the risk of an affected individual developing kernicterus.

Plasmapherersis has been used to rapidly lower bilirubin levels in the blood. Plasmapheresis is a method for removing unwanted substances (toxins, metabolic substances and plasma components) from the blood. During plasmapheresis, blood is removed from the affected individual and blood cells are separated from plasma. The plasma is then replaced with other human plasma and the blood is transfused back into the affected individual.

Liver transplantation is the only definitive treatment for individuals with Crigler-Najjar syndrome type I. Liver transplantation has drawbacks such as cost, limited availability of a donor, need for prolonged use of immunosuppressive drugs and the potential of rejection. Some physicians recommend a liver transplant if infants or children with severely elevated levels of unconjugated bilirubin do not respond to other therapy (refractory hyperbilirubinemia) or if there is a progression of neurological symptoms. Other physicians believe that liver transplantation should be performed before adolescence as preventive therapy, before brain damage can result from early onset kernicterus.

Crigler-Najjar syndrome type II responds to treatment with phenobarbital. In some instances, during an episode of severe hyperbilirubinemia, individuals with Crigler-Najjar syndrome type II may need phototherapy. Some affected individuals may not require any treatment, but should be monitored routinely.

Genetic counseling is recommended for affected individuals and their families. Psychosocial support for the entire family is essential as well. Other treatment is symptomatic and supportive.

Lifestyle changes & home remedies

What are some lifestyle changes or home remedies that can help me manage Crigler-Najjar Syndrome?

If you have any questions, please consult with your doctor to better understand the best solution for you.

 

Hello Health Group does not provide medical advice, diagnosis or treatment.

Sources

Review Date: August 17, 2018 | Last Modified: August 17, 2018

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