Crigler-Najjar syndrome is a very rare genetic condition that causes the buildup of bilirubin in your body. If left untreated, this buildup can lead to problems like brain injury.
Crigler-Najjar syndrome is extremely rare, affecting about
Crigler-Najjar syndrome is divided into type 1 and type 2 depending on its severity. Type 1 is more severe due to a higher buildup of bilirubin and less enzyme activity.
Keep reading to learn more about Crigler-Najjar syndrome is including types, symptoms, and treatment options.
Crigler-Najjar syndrome is a genetic condition caused by genes inherited from your parents. It’s been linked to certain mutations in the UGT1A1 gene, which cause reduced activity of the enzyme UDP-glucuronosyltransferase (UGT), which normally breaks down bilirubin.
Reduced activity of this enzyme causes the buildup of bilirubin in your body.
Crigler-Najjar syndrome is inherited in an autosomal recessive manner, meaning you need to receive an associated gene mutation from both parents to develop it.
Crigler-Najjar syndrome is divided into two types depending on the level of activity of this enzyme.
Type 1
Crigler-Najjar syndrome type 1 (CN1) tends to be more serious and is characterized by the complete or almost complete inactivity of UGT. People with type 1 have unconjugated bilirubin levels over 20 mg/dL. Unconjugated means it’s not bound to the protein albumin.
It often causes life threatening and severe jaundice within weeks of birth and is fatal without treatment. Individuals with this type may need a liver transplant.
Type 2 (Arias syndrome)
People with Crigler-Najjar syndrome type 2 (CN2) have a reduction in normal UGT enzyme activity and bilirubin levels between 3.5 and 20mg/dL.
Type 2 causes milder symptoms, and individuals with this type may have jaundice that comes and goes and that may worsen during times of stress. Treatment generally involves things such as medications like phenobarbital to help prevent bilirubin from building up in the blood, managing stress, and sometimes a type of blood transfusion called plasmapheresis that helps replace plasma in your blood
It’s rare for people with CN2 to develop permanent neurological injury.
The first signs of type 1 usually appear shortly after birth, with jaundice being the first sign. Jaundice is characterized by yellowing of the:
- skin
- mucous membranes
- eye whites
Infants with type 1 Crigler-Najjar syndrome are at risk of developing a complication called kernicterus or bilirubin encephalopathy. Kernicterus is a life threatening condition. where the buildup of bilirubin accumulates in the brain and causes injury. Infants with these complications may develop:
Type 2 Crigler-Najjar syndrome is milder. Symptoms tend to be milder or may not be apparent.
Crigler-Najjar syndrome is a genetic condition caused by inherited genes. It’s been linked to variants in the UGT1A1 gene.
It’s inherited in a recessive manner, meaning you need an associated gene from both parents.
The main risk factor for Crigler-Najjar syndrome is having parents with associated genes.
Your parents might not know that they carry these genes if they don’t have Crigler-Najjar syndromethemselves.
Crigler-Najjar syndrome type 1 is often diagnosed within the first few days of life in infants who develop jaundice. Blood tests can confirm high levels of bilirubin in the absence of red blood cell breakdown, and urine tests usually show a lack of bilirubin
Molecular genetic testing with a blood sample can confirm the diagnosis by identifying an associated mutation of the UGT1A1 gene.
When to seek emergency care
It’s important to seek emergency medical care if your infant develops symptoms such as:
- severe jaundice
- lethargy
- poor feeding
- seizure
- muscle spasms
Treatment for Crigler-Najjar syndrome largely centers around trying to control elevated bilirubin levels and restoring UGT1A1 gene activity.
Early treatment is needed for Crigler-Najjar syndrome type 1 to prevent kernicterus in the first months of life.
Phototherapy
The main treatment for infants with type 1 is aggressive phototherapy, in which their bare skin is exposed to intense light with their eyes shielded. This changes the bilirubin in the skin so that it can be excreted. Phototherapy tends to be less effective in older children due to their thicker skin.
Children with type 1 may require phototherapy for 10 to 12 hours per day.
Plasmaphereses
Plasmapheresis is the most effective treatment for removing excess bilirubin from the blood. It involves removing blood and separating blood cells from plasma. The plasma is then replaced with other human plasma and transfused back.
Phenobarbital medications
Phenobarbital medications stimulate the production of the enzyme that breaks down bilirubin. It may reduce bilirubin levels by
Liver and hepatocyte transplant
Liver transplant is the only permanent treatment for Crigler-Najjar syndrome, but it’s limited by cost and donor availability.
Hepatocyte transplantation is a promising alternative where healthy liver cells called hepatocytes are infused into the portal vein.
Emergency treatment
If bilirubin levels reach toxic levels, emergency treatments need to be initiated promptly. You may receive:
- aggressive hydration through an IV
- albumin
- plasmaphereses
- fat-rich food, ursodeoxycholic acid, or calcium carbonate to trap bilirubin in the intestines
Emerging therapies
Researchers are investigating a gene therapy that may cure Crigler-Najjar syndrome. Gene therapy involves injecting the missing gene to tell your body to produce the missing enzyme.
A phase ½ clinical trial is expected to be completed in 2030.
Crigler-Najjar type 1 can be more difficult to manage, with about
CN2 often causes mild symptoms and rarely causes brain injury. Some people may live into adulthood without any noticeable symptoms.
Crigler-Najjar syndrome is a very rare genetic condition characterized by the buildup of bilirubin in your body. People with type 1 often develop severe complications that can lead to brain injury in early childhood. Type 2 is generally mild and rarely causes brain injury.
It’s important to seek medical attention immediately if your child develops jaundice or other concerning symptoms. There are many reasons why a child may develop jaundice, and not all of them are serious, but it’s important for them to receive a proper diagnosis.