Crigler–Najjar syndrome

Crigler–Najjar syndrome is a rare inherited disorder in which deficient bilirubin conjugation causes severe unconjugated hyperbilirubinemia. It ranges from near-total loss of enzyme activity to a milder, treatment-responsive form.

UGT1A1: UGT1A1 is the liver enzyme that conjugates bilirubin, making it water-soluble for excretion. Variants that impair this enzyme cause the bilirubin conjugation defect in Crigler–Najjar syndrome.
Crigler–Najjar syndrome type I: Crigler–Najjar syndrome type I is the severe form, with near-absent bilirubin-conjugating enzyme activity. It typically causes very high bilirubin levels and does not respond to phenobarbital.
Neonatal jaundice: Neonatal jaundice is yellowing of an infant’s skin and eyes caused by elevated bilirubin in the blood. Crigler–Najjar syndrome often becomes apparent as unusually severe or persistent jaundice soon after birth.
Autosomal recessive inheritance: Autosomal recessive inheritance occurs when a person inherits disease-causing variants in both copies of an autosomal gene. Crigler–Najjar syndrome typically develops when both UGT1A1 copies carry pathogenic variants.
Bilirubin: Bilirubin is a yellow pigment produced chiefly when heme from aging red blood cells is broken down. Its unconjugated form accumulates when the syndrome prevents efficient liver conjugation.
Crigler–Najjar syndrome type II: Crigler–Najjar syndrome type II is a milder form with residual bilirubin-conjugating enzyme activity. Its lower bilirubin levels and phenobarbital response distinguish it from type I.
Exchange transfusion: Exchange transfusion replaces an infant’s blood with donor blood to rapidly lower bilirubin and remove antibody-coated cells. It can be used urgently when severe bilirubin elevation threatens neurologic injury.
Hyperbilirubinemia: Hyperbilirubinemia is an abnormally high concentration of bilirubin in the blood. The syndrome is a genetic cause of marked hyperbilirubinemia, specifically involving unconjugated bilirubin.
Bilirubin conjugation: Bilirubin conjugation attaches glucuronic acid to bilirubin, increasing its water solubility and enabling biliary excretion. This is the specific metabolic step deficient in the syndrome.
Gilbert syndrome: Gilbert syndrome is a common, mild inherited reduction in bilirubin conjugation that causes intermittent unconjugated hyperbilirubinemia. It affects the same enzyme pathway but usually produces far less bilirubin elevation and no severe neurologic risk.

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