Unconjugated hyperbilirubinemia that worsens with fasting due to reduced hepatic conjugation most likely indicates which syndrome?

• A. Crigler-Najjar syndrome
• B. Rotor syndrome
• C. Gilbert syndrome
• D. Dubin-Johnson syndrome

Answer: (C)

The pattern described reflects a mild, hereditary deficiency in hepatic bilirubin conjugation that worsens with fasting. This is Gilbert syndrome. In Gilbert, the liver has reduced activity of the enzyme that conjugates bilirubin (UDP-glucuronosyltransferase). When someone fasts or experiences stress, the already limited conjugation capacity is further challenged, leading to a rise in unconjugated bilirubin and mild jaundice. Liver enzymes are typically normal and the jaundice is episodic and harmless.

Crigler-Najjar would cause much more pronounced unconjugated bilirubin, often in infancy, and carries risk of kernicterus. Rotor and Dubin-Johnson syndromes produce conjugated hyperbilirubinemia due to problems with excretion or transport of conjugated bilirubin, and they usually present differently (including darker urine from conjugated bilirubin).