Crigler-Najjar Syndrome

Key Features

• Type 1: rapid severe unconjugated hyperbilirubinemia (> 30–40 mg/dL) with neurologic consequences (kernicterus)

• Type 2

  • Milder than type 1

  • Rarely associated with neurologic complications

Clinical Findings

• Type 1

  • Consanguinity is often present

  • Neurologic signs may not develop until adolescence or early adulthood, at which time deterioration may occur suddenly

• Type 2

  • Hyperbilirubinemia is less severe

  • Bile is pigmented and contains small amounts of bilirubin monoglucuronide and diglucuronide

Diagnosis

• Type 1

  • May be useful to obtain a duodenal bile specimen; findings include

    • Being colorless

    • Containing a predominance of unconjugated bilirubin, small amounts of monoconjugates, and only traces of unconjugated bilirubin

• Liver biopsy findings and liver function tests are consistently normal

• Type 2

  • Liver biopsy findings and liver function tests are consistently normal

Treatment

• Type 1

  • Exchange transfusions are required followed by phototherapy

  • A combination of aggressive phototherapy and cholestyramine may keep bilirubin levels below 25 mg/dL

  • Orlistat therapy may decrease bilirubin in a subset of patients

  • Liver transplantation is curative and may prevent kernicterus if performed early

  • Auxiliary orthotopic transplantation also relieves the jaundice while the patient retains native liver

• Type 2

  • Phenobarbital (4 mg/kg/d in infants) lowers serum bilirubin levels

  • An increased proportion of monoconjugated and diconjugated bilirubin in the bile follows phenobarbital treatment