Crigler-Najjar Syndrome
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Overview
Crigler-Najjar Syndrome (CNS) is a rare inherited disorder that affects the liver’s ability to process bilirubin, a yellow substance produced during the breakdown of red blood cells. CNS is caused by mutations in the UGT1A1 gene, which encodes an enzyme essential for converting toxic unconjugated bilirubin into a form that can be eliminated from the body. Without this enzyme, bilirubin builds up in the blood, leading to jaundice and potentially dangerous complications.
There are two types of CNS:
Type I, where the enzyme is nearly or completely absent, causing severe symptoms.
Type II, where enzyme activity is reduced but not absent, leading to milder symptoms.
The most common cause, as it significantly reduces the liver’s ability to function.
Sudden loss of liver function due to factors like viral hepatitis, drug overdose, or toxins.
High blood pressure in the liver can lead to the diversion of blood around the liver, allowing toxins to bypass detoxification.
Bleeding in the intestines can increase the amount of toxins that the liver must process.
Infections, especially bacterial infections in people with liver disease, can trigger or worsen HE.
Imbalances in sodium, potassium, and other electrolytes may also contribute to HE development.
What Causes Crigler-Najjar Syndrome?
CNS is caused by mutations in the UGT1A1 gene, inherited in an autosomal recessive pattern. This means a child must inherit a defective gene from both parents to develop the syndrome. If only one gene is inherited, the child may have Gilbert’s Syndrome, a milder condition.
Who is Impacted by Crigler-Najjar Syndrome?
CNS is extremely rare, affecting less than 1 in 1 million newborns worldwide. Because it is genetic, both parents must carry the mutation for their child to be affected.
What Are the Symptoms of CNS?
Type I CNS symptoms appear shortly after birth and include:
- Severe jaundice (yellowing of skin, eyes, and mucous membranes) persisting beyond three weeks.
- Risk of kernicterus (bilirubin encephalopathy), a life-threatening brain damage caused by bilirubin buildup. Early signs of kernicterus include lethargy, vomiting, poor feeding, and fever.
- Neurological symptoms such as muscle spasms, high-pitched crying, weak sucking, abnormal muscle tone (“floppiness”), and involuntary movements.
Kernicterus can lead to long-term disabilities including hearing loss, motor difficulties, and cognitive impairment.
Type II CNS symptoms are milder and may present later in life. Jaundice may worsen during illness, fasting, or anesthesia. Kernicterus is rare but can occur in stressful situations.
How is CNS Diagnosed?
Diagnosis involves:
- Observation of persistent severe jaundice soon after birth.
- Blood tests showing high unconjugated bilirubin with low conjugated bilirubin.
- Genetic testing for mutations in the UGT1A1 gene.
- Family history and clinical evaluation support diagnosis.
How is CNS Treated?
Type I CNS treatment:
- Phototherapy: Exposure to blue LED light breaks down bilirubin so it can be eliminated without the enzyme. Requires 10-12 hours daily and becomes less effective over time as skin thickens.
- Liver transplantation: The only curative treatment, providing a new liver capable of producing the enzyme to properly process bilirubin.
Type II CNS treatment:
- Usually managed with daily phenobarbital to increase residual enzyme activity.
Phototherapy may be needed during severe bilirubin spikes.
What is the Prognosis?
- Patients with Type II CNS can live relatively normal lives with proper treatment and monitoring.
- Those with Type I CNS face significant risks of brain damage and require urgent, ongoing treatment and early consideration for liver transplant.
How Can Liver Transplantation Portal Help You?
At Liver Transplantation Portal, we provide expert guidance and connect patients and families affected by Crigler-Najjar Syndrome to leading hepatologists and transplant centers. We support you through diagnosis, treatment, and the liver transplant process to ensure the best possible care.
Why Choose Liver Transplantation Portal?
We are committed to offering compassionate, specialized care for rare liver disorders like CNS. With access to top medical professionals and transplant services, Liver Transplantation Portal helps you navigate complex treatment pathways and access life-saving transplantation when needed.
Contact us today to learn more about Crigler-Najjar Syndrome and how we can assist you on your liver health journey.