Crigler-Najjar Syndrome

What is Crigler-Najjar syndrome?

High levels of toxic bilirubin in your blood cause Crigler-Najjar syndrome, a rare genetic condition. Bilirubin is a substance that forms when red blood cells reach the end of their lifespan. Your liver breaks down bilirubin from a toxic substance to a nontoxic substance that you get rid of in your stool. If you’re diagnosed with Crigler-Najjar syndrome, your liver can’t break down bilirubin and it collects in your blood. As a result, Crigler-Najjar syndrome can cause life-threatening symptoms if left untreated.

What are the types of Crigler-Najjar syndrome?

There are two types of Crigler-Najjar syndrome:

• Type 1 (CN1): Crigler-Najjar syndrome type 1 is very severe and life-threatening. Most children diagnosed with this condition don’t survive past childhood from complications of the condition.
• Type 2 (CN2): Crigler-Najjar syndrome type 2 is less severe than type 1. Children diagnosed with type 2 have a normal life expectancy due to mild symptoms.

Who does Crigler-Najjar syndrome affect?

Crigler-Najjar syndrome can affect anyone, as it is a genetic condition. You can inherit the condition from your parents during conception if they both give you a copy of the UGT1A1 mutated gene (autosomal recessive). If only one parent passes the mutated gene onto you, the mutation could cause a less severe syndrome called Gilbert’s syndrome.

How common is Crigler-Najjar syndrome?

Crigler-Najjar syndrome is rare and affects less than 1 in 1 million newborns across the world.

How does Crigler-Najjar syndrome affect my child’s body?

Your child will likely experience jaundice, where their skin and the whites of their eyes turn yellow. This is a symptom of the condition caused by their liver not working effectively. Jaundice is common among newborns, but children diagnosed with Crigler-Najjar syndrome will have jaundice longer than children who don’t have the condition.

Crigler-Najjar syndrome can cause life-threatening symptoms. If there’s too much bilirubin in your child’s body, it can cause irreversible brain damage. Your child’s healthcare provider will offer a treatment plan that’s unique to their symptoms to prevent life-threatening consequences of the condition.

What are the symptoms of Crigler-Najjar syndrome?

Symptoms of Crigler-Najjar syndrome range in severity based on the type, with type 1 being the most severe. Newborns with Crigler-Najjar syndrome will experience jaundice, where they have a yellow tint to their skin and eyes. It’s common for newborns to experience jaundice because their livers aren’t fully developed. This normally resolves during the first week of life. Children with Crigler-Najjar syndrome have persistent jaundice beyond the newborn period.

Kernicterus

If there’s too much bilirubin in their brain, nerves and tissues, children diagnosed with Crigler-Najjar syndrome experience symptoms of kernicterus. Kernicterus causes brain damage and is life-threatening. These symptoms normally appear after one month or into early childhood. These symptoms can also occur later in life if treatment for Crigler-Najjar syndrome stops or another illness interrupts treatment progress.

Mild symptoms of kernicterus include:

• Clumsiness.
• Muscle spasms.
• Problems with sensory perception.
• Trouble with fine motor skills (grasping objects, fastening buttons).
• Twisting or squirming movements of their body (choreoathetosis).
• Underdeveloped enamel on teeth.

Severe symptoms of kernicterus include:

• Difficulty hearing.
• Extreme fatigue (lethargic).
• Feeding difficulties.
• Fever.
• Nausea or vomiting.
• Periods of weak muscle tone (hypotonia) and/or tight muscles (hypertonia).
• Issues with cognitive development.

What causes Crigler-Najjar syndrome?

A mutation of the UGT1A1 gene causes Crigler-Najjar syndrome. The UGT1A1 gene creates enzymes in the liver that break down bilirubin to remove it from your body.

Bilirubin is a yellow substance that forms when red blood cells reach the end of their life cycle. Bilirubin takes on two forms in your body. Unconjugated bilirubin is a toxic substance that forms from red blood cells. Your liver takes unconjugated bilirubin and breaks it down into conjugated bilirubin, the nontoxic form of the substance. Once bilirubin is in its nontoxic form, your body gets rid of it when you poop.

If you have a mutation on the UGT1A1 gene, your body can’t break down bilirubin, so its toxic form collects in your blood and tissues. If you have a toxic substance in your blood, it can cause life-threatening symptoms of Crigler-Najjar syndrome if left untreated.

How is Crigler-Najjar syndrome diagnosed?

If your baby has jaundice, with a higher bilirubin level than expected in the newborn period, or jaundice develops rapidly within the first few days to weeks after your baby is born, their healthcare provider will offer tests, in addition to a physical exam, to determine what’s causing your child’s skin and the whites of their eyes to turn yellow. Tests to diagnose Crigler-Najjar syndrome include:

• Genetic testing to identify the mutated gene responsible for symptoms.
• Blood and/or stool tests to determine how much bilirubin (unconjugated) is in their blood and stool, such as a liver function test or a complete blood count.
• Bilirubin blood test to detect how much bilirubin is in their blood.

Their healthcare provider will also ask if you have a history of genetic conditions in your family to pinpoint the diagnosis before testing.

How is Crigler-Najjar syndrome treated?

Treatment for Crigler-Najjar syndrome focuses on lowering the levels of bilirubin in your body. Treatment could include:

• Phototherapy: Phototherapy uses bright lights to remove bilirubin from your body. During this procedure, you’ll wear protective eyewear and have your skin exposed to bright lights. The lights move bilirubin through your body as waste without changing it into its non-toxic form.
• Taking medicine to treat infections or illnesses that cause fever.
• Plasmapheresis: Plasmapheresis removes toxic substances from the blood via a blood transfusion that removes the plasma from your blood and replaces it with healthy plasma, often from a donor.
• Liver transplant: A surgical procedure to remove your liver and replace it with a donor’s healthy liver. This is an effective treatment for Crigler-Najjar syndrome type 1 and usually occurs before adolescence to prevent brain damage.
• Taking phenobarbitalto prevent bilirubin from building up in your blood (hyperbilirubinemia). This treatment is effective for Crigler-Najjar syndrome type 2.

Are there side effects of the treatment?

While very effective for treating Crigler-Najjar syndrome, exposing your skin to fluorescent light or sunlight can increase your risk of being exposed to ultraviolet radiation that can lead to skin cancer. The new technology that uses LED blue lights (similar to the light that emits from your phone screen) reduces your exposure to ultraviolet radiation and is the safest treatment option.

As you age and grow, phototherapy might become ineffective to treat Crigler-Najjar syndrome because your body mass increases, which causes your skin to thicken. This makes it more difficult for light to reach bilirubin molecules.

How do I take care of my child during Crigler-Najjar syndrome treatment?

The most common treatment for symptoms of Crigler-Najjar syndrome is phototherapy. Children diagnosed with this condition will need to spend time under phototherapy lights to remove bilirubin from their body to prevent it from collecting in their blood and reducing jaundice. Most often, infants will need to sleep under phototherapy lights a few times a week to a few times a month. It can be difficult to put children to sleep under bright lights, even with light-blocking eye protection. Offer comfort to your child during their treatments by talking to them or touching them until they adjust to the lights and can sleep. Proper hydration is essential.

How can I prevent Crigler-Najjar syndrome?

You can’t prevent Crigler-Najjar syndrome because it’s a genetic condition. If you plan on becoming pregnant and want to understand your risk of having a child with a genetic condition, talk with your healthcare provider about genetic testing.

What can I expect if I have Crigler-Najjar syndrome?

Children diagnosed with Crigler-Najjar syndrome type 2 will have a good prognosis if their condition receives treatment early to prevent life-threatening symptoms.

Severe cases of Crigler-Najjar syndrome type 1 have a poorer prognosis if the condition isn’t diagnosed and treated within the first few months of life. In these cases, children are at risk of life-threatening symptoms that prevent them from living beyond two years.

Most people diagnosed with Crigler-Najjar syndrome will need lifelong treatment and management of the condition. With effective treatment, they’ll have a normal lifespan.

Is there a cure for Crigler-Najjar syndrome?

Studies show that a liver transplant could cure Crigler-Najjar syndrome. During a liver transplant, a healthy donor’s liver replaces your liver during a lengthy surgical procedure. The outcome of a liver transplant for a person diagnosed with Crigler-Najjar syndrome is to prevent life-threatening symptoms like brain damage from occurring. As the cells and enzymes in your liver can’t break down bilirubin, replacing your liver with a liver that can break down bilirubin is an effective treatment option.

When should I see my healthcare provider?

Crigler-Najjar syndrome can cause irreversible, life-threatening symptoms. If you notice any symptoms of the condition affecting your child’s ability to thrive, contact their healthcare provider. Additional symptoms to look out for include:

• Developmental delays.
• High fever.
• Jaundice that won’t go away after phototherapy.
• Trouble eating.

What questions should I ask my doctor?

• How long does my child need phototherapy treatment?
• Are there side effects to the treatment you recommended?
• Does my child need a liver transplant?
• How serious is my child’s diagnosis?
• Can my child do phototherapy at home?

A note from Cleveland Clinic

A Crigler-Najjar syndrome diagnosis can be challenging for both children and their caretakers. It may be scary to see your child have a yellow hue to their skin and eyes after they’re born. While you’re taking care of your child during their diagnosis, make sure you take care of yourself if you feel overwhelmed, stressed or anxious by talking with a mental health professional. When you’re feeling your best, you’ll be able to care for your child to help them feel their best as well.