Congenital Hyperbilirubinemia
Geoffrey W. Smith
Gilbert's Syndrome
Gilbert's syndrome is an unconjugated hyperbilirubinemia in the presence of normal erythrocyte life span. It occurs occasionally in humans and has been described in Southdown sheep.1 Gilbert's syndrome involves a failure of unconjugated bilirubin to cross the liver cell membrane and be conjugated.
This is most likely due to a defect in carrier proteins or the conjugating enzyme.2 Hepatic bilirubin clearance is about 30% of normal when tested with a loading dose of radiolabeled bilirubin.3Affected Southdown sheep may show icterus or at least elevated plasma bilirubin levels, both conjugated and unconjugated. Affected sheep also cannot excrete BSP into the bile. No histopathologic lesions are present, other than some pigment in the hepatocytes. The condition is inherited as an autosomal dominant trait in humans.2 The bile acid levels are normal in humans, but one sheep exhibited defects in hepatic bile acid clearance.4
Dubin-Johnson Syndrome
Dubin-Johnson syndrome is a failure of conjugated bilirubin to enter the bile canaliculi. This has been diagnosed sporadically in humans and in Corriedale sheep.5 There may be an impairment not only in bilirubin but also in excretion of other conjugated organic anions. Sheep affected by this syndrome may be jaundiced or have hyperbilirubinemia. Both conjugated and unconjugated bilirubin are increased, and BSP clearance is delayed. Bile acids are reported to be normal in humans, but delayed clearance was reported in three Corriedale sheep.4 Histologically, the hepatocytes contain a black, melanin-like pigment.5
Persistent Hyperbilirubinemia in Thoroughbreds
A persistent hyperbilirubinemia has been reported in a Thoroughbred racehorse that had no evidence of liver damage, cholestasis, or hemolysis and was not fasting.6 The horse was persistently icteric and had serum total bilirubin concentrations of 8.7 to 9.4 mg/dL; 90% or more of the plasma bilirubin was the unconjugated form. Serum bile acid concentration, along with the liver enzymes GGT, AST, and SDH, were within normal limits. The horse acted clinically normal, and the plasma fatty acid concentration was also within normal limits. The condition was similar to Crigler-Najjar syndrome type 2 in humans, which involves a deficiency in bilirubin uridine diphosphate glucuronyltransferase needed to conjugate bilirubin, but this was not verified.