Clinical Information

Dubin-Johnson syndrome (DJS) and Rotor syndrome are 2 of the inherited disorders of bilirubin metabolism that result in conjugated hyperbilirubinemia. DJS is inherited as an autosomal recessive trait that is rarely detected before puberty. It is characterized by chronic, nonhemolytic jaundice. Most patients are asymptomatic and the liver typically shows abnormal black pigmentation. The gene responsible for this disorder is a member of the family of ATP-binding cassette transporters located on chromosome 10q24, called MRP2 or cMOAT. This defect impairs liver excretion of conjugated bilirubin and several organic anions from the hepatocytes into the bile. Other liver function tests are normal.

Rotor syndrome is a rare condition of the liver and very similar to DJS. It is inherited as an autosomal recessive trait caused by digenic inheritance of homozygous mutations in the SLCO1B1 and SLCO1B3 genes. Biochemically, Rotor syndrome can be distinguished from DJS by a normal functioning gallbladder, normal liver histology, and the different pattern of coproporphyrin isomers excretion.

In healthy individuals, the percent of coproporphyrin I excreted relative to the total coproporphyrin excreted in urine is approximately 20% to 45%. In DJS and Rotor syndrome, retention of coproporphyrin III by the liver causes diminished urinary excretion. Consequently the percent of coproporphyrin I to the total coproporphyrin excreted in the urine exceeds the normal range.

When the total urinary excretion of coproporphyrin is elevated and the percent of coproporphyrin I to total coproporphyrin exceeds 60%, but is less than 80%, the presentation is most consistent with Rotor syndrome. In patients with DJS, the percentage of coproporphyrin I to total coproporphyrin is typically greater than 80% and the total urinary coproporphyrin excretion is within normal limits. Some overlap may exist so the ratio alone should not be used to distinguish between Rotor or DJS.