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Inherited disorders associated with conjugated hyperbilirubinemia

Jayanta Roy-Chowdhury, MD, MRCP
Namita Roy-Chowdhury, PhD
Section Editor
Keith D Lindor, MD
Deputy Editor
Shilpa Grover, MD, MPH, AGAF


Conditions that cause hyperbilirubinemia can be classified into those that result in a predominantly unconjugated hyperbilirubinemia and those that are associated with an elevation of both conjugated and unconjugated forms of bilirubin. (See "Classification and causes of jaundice or asymptomatic hyperbilirubinemia".)

Excretion of conjugated bilirubin is impaired in a number of acquired conditions (such as alcoholic and viral hepatitis, biliary obstruction, cholestasis of pregnancy) and in inherited disorders (such as Dubin-Johnson syndrome, Rotor syndrome, benign recurrent intrahepatic cholestasis). This topic review will discuss the inherited disorders associated with conjugated hyperbilirubinemia. The other conditions are presented separately. (See appropriate topic reviews).


Elimination of conjugated bilirubin in bile is affected in several inherited disorders that work through different mechanisms. In all these situations, the abnormality of biliary excretion of bilirubin is shared with excretory defect of all or some other organic anions. Inherited syndromes of intrahepatic cholestasis commonly result from mutations in the following genes: SERPINAI (alpha 1- antitrypsin), JAG1 (causing Alagille syndrome), ATP8B1 (also known as FIC1), ABCB11 (bile salt export pump [BSEP]), MDR3 (ABCB4), and MRP2 (causing Dubin-Johnson syndrome). The genetic basis of Rotor syndrome has not been identified [1].

Although Dubin-Johnson syndrome and Rotor syndrome have similar phenotypes (mild, fluctuating elevation of both unconjugated and conjugated bilirubin in plasma), in Dubin-Johnson syndrome biliary excretion of organic anions, except bile acids, is impaired, while Rotor syndrome is a disorder of hepatic storage. Other inherited conditions, like progressive familial intrahepatic cholestasis and benign recurrent intrahepatic cholestasis, cause conjugated hyperbilirubinemia as a consequence of reduced bile flow [2].


In 1954, Dubin and Johnson [3] and Sprinz and Nelson [4] described patients with predominantly conjugated chronic hyperbilirubinemia that was not associated with hemolysis. The disorder occurs in all races and nationalities and both sexes [4-7]. It is rare except in Sephardic Jews in whom the incidence is approximately 1:3000 [7].

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Literature review current through: Nov 2017. | This topic last updated: Nov 06, 2017.
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