Inherited hyperbilirubinaemia syndromes

What it is

Four genetic bilirubinemia syndromes are grouped together, and the first split between them is which bilirubin rises. Gilbert syndrome and Crigler-Najjar syndrome give an unconjugated hyperbilirubinemia, because the defect is in conjugation. Dubin-Johnson syndrome and Rotor syndrome give a conjugated hyperbilirubinemia, because the defect is in the secretion of bilirubin.

How it presents

• Gilbert syndrome: UDP-glucuronyl transferase deficiency, caused by mutation of the promoter region of glucuronosyltransferase. Asymptomatic, with a mild increase in bilirubin of 1 to 6 mg/dL and other LFT normal. The rise appears with stress such as exercise or surgery, and with fasting.
• Crigler-Najjar syndrome: permanent deficiency of glucuronosyltransferase, in 2 types. Type 2 responds to enzyme induction by phenobarbital; type 1 does not respond and often leads to kernicterus.
• Dubin-Johnson syndrome and Rotor syndrome: conjugated hyperbilirubinemia with a defect in the secretion of bilirubin. Dubin-Johnson results in a black liver.