This patient had self-resolving scleral icterus and isolated indirect hyperbilirubinemia associated with a period of stress.  These findings are consistent with Gilbert syndrome, the most common inherited disorder of bilirubin metabolism.

Normal bilirubin metabolism begins with hepatic uptake of unconjugated bilirubin produced from red blood cell turnover.  Within the liver, UDP glucuronosyltransferase conjugates bilirubin with glucuronic acid, after which conjugated bilirubin is excreted into bile canaliculi.

In Gilbert syndrome, a genetic mutation results in reduced enzymatic activity of UDP glucuronosyltransferase and therefore decreased bilirubin conjugation (Choices B and D).  Triggers associated with increased bilirubin production (eg, stress, illness, hemolysis) result in episodic exacerbations of indirect hyperbilirubinemia, as seen in this patient.  Because bilirubin excretion into the bile duct is normal in Gilbert syndrome, hepatocyte bilirubin storage is also normal, as is liver histology (Choices A and E).

Notably, impaired bilirubin conjugation also occurs in Crigler-Najjar syndrome, but patients typically have severe, chronic hyperbilirubinemia that begins in the neonatal period and can be associated with bilirubin-induced neurologic dysfunction.

(Choice C)  Dubin-Johnson syndrome is a benign, inherited disorder of bilirubin metabolism characterized by defective hepatic excretion of bilirubin into the biliary system.  Bilirubin conjugation is normal, but defective excretion results in increased hepatocyte storage of bilirubin, resulting in dense liver pigmentation.  Although patients often have recurrent episodes of scleral icterus, elevated direct bilirubin is expected due to reflux of conjugated bilirubin back into the plasma.

Educational objective:
Gilbert syndrome is characterized by indirect hyperbilirubinemia due to decreased bilirubin conjugation.  Patients have recurrent, self-resolving episodes of scleral icterus and jaundice triggered by stress.