Which syndrome presents with intermittent unconjugated hyperbilirubinemia that worsens with fasting?

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

Answer: (B)

Intermittent unconjugated hyperbilirubinemia that worsens with fasting is Gilbert syndrome. This condition involves a mild decrease in hepatic UDP-glucuronosyltransferase activity due to a promoter polymorphism in the UGT1A1 gene, leading to reduced conjugation of bilirubin. As a result, bilirubin remains unconjugated and can rise when something increases bilirubin load or decreases clearance, such as fasting, illness, or dehydration. Liver enzymes are typically normal and there’s no hemolysis, and many people are asymptomatic except for transient jaundice during stress or fasting.

Crigler-Najjar would cause more severe, often persistent unconjugated hyperbilirubinemia with higher risk of kernicterus, not just intermittent elevations. Rotor and Dubin-Johnson cause predominantly conjugated hyperbilirubinemia and have different clinical features (including dark liver pigment in Dubin-Johnson) that don’t fit the pattern described.