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Differential diagnosis of hyperbilirubinemia syndromes between Dubin-Johnson syndrome and Rotor syndrome in patients > or =1 year of age
Investigation of inherited conjugated hyperbilirubinemia syndromes (Dubin-Johnson syndrome, Rotor syndrome) only.
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 adenosine triphosphate (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 benign 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.
COPROPORPHYRIN ISOMERS I AND III
25-150 mcg/24 hours
8-110 mcg/24 hours
% COPROPORPHYRIN I
Abnormal results are reported with a detailed interpretation including an overview of the results and their significance, a correlation to available clinical information provided with the specimen, differential diagnosis, and recommendations for additional testing when indicated and available, and a phone number to reach one of the laboratory directors in case the referring physician has additional questions.
This test is not useful for the evaluation of individuals <1 year of age suspected of having Dubin-Johnson syndrome or Rotor syndrome. Due to normal liver development, coproporphyrin I is primarily excreted in infant urine and cannot be interpreted in the scope of hyperbilirubinemia syndromes.
This test is not useful for evaluating patients with suspected porphyrias. For measurement of urine coproporphyrin and uroporphyrin for the workup of porphyria, see PQNU / Porphyrins, Quantitative, 24 Hour, Urine or PQNRU / Porphyrins, Quantitative, Random, Urine.
Failure to maintain low temperature and correct pH may allow analyte degradation and result in falsely decreased coproporphyrin III values (ie, false-positives).
1. Koskelo P, Mustajoki P: Altered coproporphyrin-isomer excretion in patients with the Dubin-Johnson syndrome. Int J Biochem 1980;12:975-978
2. Chowdhury J, Wolkoff AW, Chowdhury N, Arias IM: Hereditary Jaundice and Disorders of Bilirubin Metabolism. In Online Metabolic and Molecular Bases of Inherited Disease. Edited by D Valle, AL Beaudet, B Vogelstein, et al. New York, McGraw-Hill; 2014. Accessed July 06, 2016. Available at http://ommbid.mhmedical.com/content.aspx?bookid=971&Sectionid=62639411