Crigler-Najjar Syndrome
A rare inherited inability to process bilirubin
Quick Facts
- Type: Inherited metabolic liver disorder
- Cause: Missing or reduced bilirubin enzyme
- Onset: From birth
- Types: Type 1 (severe) and Type 2 (milder)
Overview
Crigler-Najjar syndrome is a rare inherited disorder in which the liver lacks enough of the enzyme needed to process bilirubin, the yellow pigment produced when red blood cells break down. Normally this enzyme attaches bilirubin to another molecule so it can be removed in bile. In Crigler-Najjar syndrome the enzyme is missing or severely reduced, so unconjugated bilirubin builds up in the blood and causes jaundice from the first days of life.
There are two forms. Type 1 is the most severe, with little or no enzyme activity and dangerously high bilirubin levels that require lifelong treatment. Type 2 is milder, with some enzyme activity, lower bilirubin levels, and a better outlook. The condition is distinct from the common, harmless Gilbert syndrome, which involves only a slight reduction in the same enzyme.
Symptoms
The hallmark is persistent, marked jaundice that begins in the newborn period and does not resolve like ordinary newborn jaundice.
- Pronounced yellowing of the skin and the whites of the eyes, present from birth
- Jaundice that persists and, in type 1, reaches very high bilirubin levels
- In severe, untreated cases, signs of bilirubin affecting the brain (kernicterus), such as poor feeding, unusual sleepiness, a high-pitched cry, stiffening or arching of the body, or seizures
Type 2 causes milder, more variable jaundice and a much lower risk of brain involvement. Type 1, if untreated, carries a serious risk of brain damage from extremely high bilirubin.
Causes
Crigler-Najjar syndrome is caused by inherited changes in the UGT1A1 gene, which provides instructions for the enzyme that processes bilirubin in the liver.
- Type 1: the enzyme is essentially absent, so bilirubin cannot be processed and rises to very high levels.
- Type 2: some enzyme activity remains, so bilirubin still builds up but to a lesser, less dangerous degree.
The condition is inherited in an autosomal recessive pattern, meaning a child must inherit an altered copy of the gene from each parent. Parents who each carry one altered copy usually have no symptoms themselves.
Risk Factors
- Two parents who each carry a UGT1A1 gene change (carriers)
- A family history of Crigler-Najjar syndrome
- Parents who are blood relatives, which increases the chance of inheriting two altered copies
Diagnosis
Diagnosis is suspected when a newborn has severe, persistent unconjugated jaundice without another explanation.
- Bilirubin testing: markedly elevated unconjugated (indirect) bilirubin with normal other liver tests and no evidence of red cell breakdown.
- Excluding other causes: tests to rule out blood-group incompatibility, hemolysis, and bile duct problems.
- Genetic testing: identifies changes in the UGT1A1 gene and confirms the diagnosis.
- Response to medication: a trial of a medicine called phenobarbital can help distinguish type 2 (which responds) from type 1 (which does not).
Treatment
Treatment aims to keep bilirubin at safe levels and prevent brain injury. It differs by type.
- Phototherapy: the mainstay for type 1; special light breaks down bilirubin in the skin and is often needed for many hours a day, including at home.
- Medication: phenobarbital can lower bilirubin in type 2 by boosting the limited enzyme activity.
- Exchange transfusion: used urgently when bilirubin rises to dangerous levels.
- Liver transplant: the only definitive cure for type 1, considered because phototherapy becomes less effective as a child grows.
Children with type 1 need close, lifelong specialist care. Type 2 is usually managed more easily and carries a much better outlook.
Prevention
Crigler-Najjar syndrome cannot be prevented because it is inherited. For families with a known history, the focus is on awareness and early management:
- Genetic counseling for couples with a family history or known carrier status
- Prompt evaluation of any newborn with severe or persistent jaundice
- Close monitoring of bilirubin in an affected child to prevent dangerous rises
- Strict adherence to prescribed phototherapy and follow-up
When to See a Doctor
Any newborn with severe or persistent jaundice should be evaluated promptly. Seek emergency care if a baby or child with Crigler-Najjar syndrome develops signs that bilirubin may be affecting the brain, such as:
- Unusual sleepiness or difficulty waking
- Poor feeding, a high-pitched cry, or marked irritability
- Stiffening, arching of the body, or abnormal movements
- Seizures
These are medical emergencies. Families managing type 1 should follow their care team's instructions for monitoring and when to seek urgent help.
Frequently Asked Questions
What is the difference between Crigler-Najjar syndrome and Gilbert syndrome?
Both involve the same bilirubin-processing enzyme, but Gilbert syndrome is common and harmless with only a slight enzyme reduction, while Crigler-Najjar syndrome is rare and severe, with the enzyme largely or completely missing and bilirubin rising to high levels from birth.
Is Crigler-Najjar syndrome curable?
Type 1 can be cured only by a liver transplant, since the missing enzyme is made in the liver. Type 2 is milder and usually well controlled with medication. Phototherapy is essential for managing type 1 while awaiting or instead of transplant in some cases.
Why is high bilirubin dangerous in this condition?
Very high levels of unconjugated bilirubin can cross into the brain and cause damage, a condition called kernicterus. Preventing bilirubin from reaching dangerous levels is the main goal of treatment, especially in type 1.
How is Crigler-Najjar syndrome inherited?
It is inherited in an autosomal recessive pattern, meaning a child must receive an altered copy of the UGT1A1 gene from both parents. Carrier parents usually have no symptoms themselves.
What does treatment involve day to day?
For type 1, treatment often means several hours of phototherapy each day, careful monitoring of bilirubin, and specialist follow-up, with liver transplant considered over time. Type 2 is usually managed with medication and is much less demanding.
References
- MedlinePlus, U.S. National Library of Medicine. Crigler-Najjar syndrome.
- Genetic and Rare Diseases Information Center (GARD). Crigler-Najjar syndrome.
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK). Liver disease.
- National Organization for Rare Disorders (NORD).