Crigler-Najjar syndrome
Summary
Crigler-Najjar syndrome is a rare autosomal recessive disorder caused by deficiency or absence of UDP-glucuronosyltransferase (UGT1A1), leading to severe unconjugated hyperbilirubinemia. Type I is more severe with complete enzyme absence, while Type II has partial enzyme activity and responds to phenobarbital treatment.
Detail
Crigler-Najjar syndrome results from mutations in the UGT1A1 gene, which encodes the enzyme responsible for conjugating bilirubin in hepatocytes. Type I (complete enzyme deficiency) presents with severe jaundice from birth, with unconjugated bilirubin levels >20 mg/dL, and carries high risk of kernicterus and neurological damage. These patients require lifelong phototherapy and often liver transplantation. Type II (partial enzyme deficiency, also called Arias syndrome) presents with milder hyperbilirubinemia (6-20 mg/dL) and responds to phenobarbital, which induces residual enzyme activity. Both types show predominantly unconjugated hyperbilirubinemia with normal liver function tests and liver histology. The condition is distinguished from physiologic jaundice by its persistence and severity, and from Gilbert syndrome by much higher bilirubin levels and earlier presentation.
Sources
- Harrison's Principles of Internal Medicine
- Robbins and Cotran Pathologic Basis of Disease
- First Aid for the USMLE Step 1
- Sleisenger and Fordtran's Gastrointestinal and Liver Disease
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