CriglerNajjarSyndrom

Crigler-Najjar syndrome is a rare inherited disorder caused by a deficiency of hepatic UDP-glucuronosyltransferase (UGT1A1), the enzyme responsible for conjugating bilirubin so it can be excreted in bile. The condition leads to severe unconjugated hyperbilirubinemia and can cause neurological injury if untreated. It is inherited in an autosomal recessive pattern and results from mutations in the UGT1A1 gene.

There are two main forms. Type I Crigler-Najjar syndrome presents in infancy with near-complete loss of UGT1A1 activity and very high levels of unconjugated bilirubin, often exceeding 20 mg/dL. It does not respond to phenobarbital and carries a high risk of kernicterus without aggressive management; liver transplantation is the definitive treatment. Type II Crigler-Najjar syndrome involves partial enzyme deficiency, with lower unconjugated bilirubin levels and typically a response to phenobarbital, which induces residual UGT1A1 activity. Prognosis is generally better for type II, though lifelong monitoring is required.

Clinical features include persistent jaundice from birth, with the major risk being bilirubin-induced neurologic damage in infancy. Management focuses on preventing kernicterus and reducing bilirubin burden. In type I, treatments include intensive phototherapy, exchange transfusions as needed, and consideration of liver transplantation. In type II, phenobarbital is commonly used to induce the enzyme, often reducing bilirubin levels; phototherapy may be needed during periods of stress or illness.

Diagnosis combines measurement of bilirubin fractions, liver function tests, assessment of UGT1A1 activity, and genetic testing to identify UGT1A1 mutations. Differential diagnoses include Gilbert syndrome, which features milder unconjugated hyperbilirubinemia without such severe enzyme deficiency.