Which defect is associated with Gilbert Syndrome among hepatic B1 diseases?

• A. Mild UDPGT deficiency and defect of ligandin
• B. Total UDPGT deficiency
• C. Circulating maternal inhibitor of bilirubin conjugation
• D. Transient UDPGT deficiency

Answer: (A)

Gilbert syndrome is caused by a mild hereditary reduction in the liver’s ability to conjugate bilirubin, due to partial deficiency of the enzyme UDP-glucuronyl transferase (UGT1A1). This modest drop in UGT activity leads to intermittent unconjugated hyperbilirubinemia, especially during fasting or illness. In this hepatic B1 disorder, a defect in ligandin, the bilirubin-binding protein that helps shuttle bilirubin to the conjugation system, can accompany the UGT deficiency, explaining the reduced processing of bilirubin even further. This combination—mild UDP-glucuronosyltransferase deficiency with ligandin impairment—fits Gilbert syndrome best, describing a chronic, mild jaundice with normal liver function tests.

The other scenarios describe different conditions: complete (total) UDP-glucuronosyltransferase deficiency causes much more severe hyperbilirubinemia (Crigler-Najjar syndrome type I/II); a circulating maternal inhibitor of bilirubin conjugation is a neonatal phenomenon; transient UDP-glucuronosyltransferase deficiency likewise occurs in newborns and resolves with time.