Crigler-Najjar Syndrome Overview
Learn About Crigler-Najjar Syndrome
Crigler-Najjar syndrome is a very rare inherited disorder in which bilirubin cannot be broken down. Bilirubin is a substance made by the liver.
Glucuronyl transferase deficiency (type I Crigler-Najjar); Arias syndrome (type II Crigler-Najjar)
An enzyme converts bilirubin into a form that can easily be removed from the body. Crigler-Najjar syndrome occurs when this enzyme does not work correctly. Without this enzyme, bilirubin can build up in the body and lead to:
- Jaundice (yellow discoloration of skin and eyes)
- 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 may start later in life.
The syndrome runs in families (inherited). A child must receive a copy of the variant gene from both parents to develop the severe form of the condition. Parents who are carriers (with just one variant gene) have about one half the enzyme activity of a normal adult, but do not have symptoms.
Symptoms may include:
- 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
Light treatment (phototherapy) is needed throughout a person's life. In infants, this is done using bilirubin lights (bili or 'blue' lights). Phototherapy does not work as well after age 4, because thickened skin blocks the light.
A liver transplant can be done in some people with type I disease.
Blood transfusions may help control the amount of bilirubin in blood. Calcium compounds are sometimes used to remove bilirubin in the gut.
The drug phenobarbitol is sometimes used to treat type II Crigler-Najjar syndrome.
Federico Mingozzi practices in Evry, France. Mr. Mingozzi is rated as an Elite expert by MediFind in the treatment of Crigler-Najjar Syndrome. His top areas of expertise are Crigler-Najjar Syndrome, Rotor Syndrome, Pompe Disease, Hemophilia B, and Liver Transplant.
Giulia Bortolussi practices in Trieste, Italy. Ms. Bortolussi is rated as an Elite expert by MediFind in the treatment of Crigler-Najjar Syndrome. Her top areas of expertise are Crigler-Najjar Syndrome, Rotor Syndrome, Transient Familial Hyperbilirubinemia, Bilirubin Encephalopathy, and Liver Transplant.
Andres Muro practices in Trieste, Italy. Mr. Muro is rated as an Elite expert by MediFind in the treatment of Crigler-Najjar Syndrome. His top areas of expertise are Crigler-Najjar Syndrome, Rotor Syndrome, Transient Familial Hyperbilirubinemia, Bilirubin Encephalopathy, and Liver Transplant.
Milder forms of the disease (type II) do not cause liver damage or changes in thinking during childhood. People who are affected with a mild form still have jaundice, but they have fewer symptoms and less organ damage.
Infants with the severe form of the disease (type I) may continue to have jaundice into adulthood, and may need daily treatment. If not treated, this severe form of the disease will lead to death in childhood.
People with this condition who reach adulthood will develop brain damage due to jaundice (kernicterus), even with regular treatment. The life expectancy for someone with type I disease is 30 years.
Possible complications include:
- A form of brain damage caused by jaundice (kernicterus)
- Chronic yellow skin/eyes
Seek genetic counseling if you are planning to have children and have a personal or family history of Crigler-Najjar.
Contact your health care provider if you or your newborn infant has jaundice that does not go away.
Genetic counseling is recommended for people with a personal or family history of Crigler-Najjar syndrome who want to have children. Blood tests can identify people who carry the genetic variant.
Summary: This is a Phase 1/2, multinational, open-label, study to evaluate the safety and efficacy of an intravenous infusion of GT-UGT1A1-AAV8-02 in patients with Crigler-Najjar type 1 aged ≤10 years and requiring phototherapy. Patients will received a single administration of GT-UGT1A1-AAV8-02 and will be followed for safety and efficacy of approximately 60 months (5 years): * a follow-up of approximatel...
Summary: Clinical trial rationale: CNS is an ultra-rare (\<1/1 million newborns), autosomal recessive disorder of bilirubin conjugation caused by mutation in the gene coding for uridine 5'-diphosphate glucuronosyltransferase (UGT1A1), that causes the accumulation of neurotoxic unconjugated bilirubin (UCB). Reduction of UCB is managed with phenobarbital in mild CNS, and daily phototherapy in severe CNS. The...
Published Date: August 18, 2024
Published By: Anna C. Edens Hurst, MD, MS, Associate Professor in Medical Genetics, The University of Alabama at Birmingham, Birmingham, AL. Review provided by VeriMed Healthcare Network. Also reviewed by David C. Dugdale, MD, Medical Director, Brenda Conaway, Editorial Director, and the A.D.A.M. Editorial team.
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Kaplan M, Wong RJ, Bensen R, Sibley E, Stevenson DK. Neonatal jaundice and liver diseases. In: Martin RJ, Fanaroff AA, Walsh MC, eds. Fanaroff and Martin's Neonatal-Perinatal Medicine. 12th ed. Philadelphia, PA: Elsevier; 2025:chap 95.
Lidofsky SD. Jaundice. In: Feldman M, Friedman LS, Brandt LJ, eds. Sleisenger and Fordtran's Gastrointestinal and Liver Disease. 11th ed. Philadelphia, PA: Elsevier; 2021:chap 21.