Excerpt from Dubin-Johnson Syndrome

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Background

Dubin-Johnson syndrome (DJS) is a type of hereditary hyperbilirubinemia that was first described independently in 1954 by Dubin and Johnson and by Sprinz and Nelson.

Hereditary hyperbilirubinemias can be divided into conjugated forms and unconjugated forms. While Gilbert syndrome and Crigler-Najjar syndrome are examples of the unconjugated hyperbilirubinemias, DJS and Rotor syndrome represent the 2 types of familial conjugated hyperbilirubinemias.

Both types of conjugated hyperbilirubinemias have a relatively benign course, but establishing the diagnosis is important to spare patients from undergoing multiple unnecessary procedures and to exclude other more serious causes of hyperbilirubinemia.

Pathophysiology

DJS is an autosomal recessive disorder that is caused by a mutation in the gene responsible for the human canalicular multispecific organic anion transporter (cMOAT) protein. It is also called the multidrug resistance protein 2 (MRP2). This protein mediates ATP-dependent transport of certain organic anions across the canalicular membrane of the hepatocyte. The human MRP2 gene has been localized to band 10q23-10q24. A defect in the cMOAT (MRP2) protein results in the impaired hepatobiliary transport of non–bile salt organic anions and is thought to be responsible for the conjugated hyperbilirubinemia and for the accumulation of hepatocellular pigment.

Several different mutations in the MRP2 gene have been identified in patients with DJS. Mutations in the ATP-binding region, which is critical for the functioning of the protein, form a significant proportion of the genetic lesions identified to date. One mutation causes impaired transcription and mislocalization of the protein.

Frequency

United States

DJS is rare.

International

DJS is rare, except in Iranian Jews, in whom the prevalence is about 1:1300.

Mortality/Morbidity

Life expectancy is normal. Reduced prothrombin activity, resulting from lower levels of clotting factor VII, is found in 60% of patients with DJS.

Race

DJS has been described in all nationalities, ethnic backgrounds, and races. Prevalence reportedly is highest among Iranian Jews (1:1300). This group may have an associated deficiency in clotting factor VII that is not observed in other populations.

Sex

Both sexes are affected equally.

Age

Patients with DJS tend to develop nonpruritic jaundice during their teenaged years.

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