Crigler-Najjar syndrome is a rare autosomal recessive disorder of bilirubin metabolism caused by mutation in the UDP-glucuronosyltransferase (UDPGT) gene. Type I is characterized by complete absence of bilirubin UDPGT enzyme, resulting in severe neonatal jaundice, pure unconjugated hyperbilirubinemia, and possible kernicterus (chronic bilirubin encephalopathy). Left untreated, it leads to neurologic impairment, brain damage, and potentially, death. Patients are also at risk for bilirubin-induced neurological dysfunction (BIND). The acute presentation of BIND results in hypotonia, a high-pitched cry, and sleepiness. Continued exposure to high levels of bilirubin results in poor suck, irritability, and hypertonia with retrocollis and opisthotonos. Seizures, apnea, and respiratory failure may ensue. Kernicterus presents in a child younger than 1 year with sensory neural hearing loss, choreoathetoid cerebral palsy, gaze abnormalities, and enamel hypoplasia. Therapies include exchange transfusions, plasmapheresis, and intensive phototherapy. Liver transplantation can be therapeutic and curative. Orlistat and calcium phosphate supplementation and tin mesoporphyrin have also been used to lower bilirubin levels.

Type II, or Arias syndrome, is characterized by a reduced level of bilirubin UDPGT enzyme. It has later onset and a better prognosis. Phenobarbital treatment for type II disease reduces bilirubin levels. Liver function tests appear normal in both types of the disease.

Acute exacerbation consisting of increased bilirubin levels may be precipitated by illness, anesthesia, fasting, or cholecystitis. Appropriate treatment must be instituted to limit the rise of bilirubin levels to prevent adverse sequalae.