Dubin-Johnson Syndrome

620 Users are discussing this topic

PatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.

See also: Jaundice written for patients

Synonyms: hyperbilirubinaemia II, DJS, Sprinz-Nelson syndrome

Dubin-Johnson syndrome is a rare benign chronic disorder of bilirubin metabolism, characterised by conjugated hyperbilirubinaemia, darkly pigmented liver and the presence of abnormal pigment in hepatic parenchymal cells.[1] 

Dubin-Johnson syndrome was first described by Dubin and Johnson in 1954 and independently by Sprinz and Nelson.[2] There is no haemolysis but conjugated bilirubin is raised due to a defect on the chromosome 10q24 affecting the canalicular multispecific organic anion transporter (cMOAT) protein.[3] 

There is no elevation of other liver enzymes. There is impaired secretion of conjugated bilirubin and other non-bile salt organic anions from hepatocytes into the bile.[4] It runs a generally benign course.

NEW - log your activity

  • Notes
    Add notes to any clinical page and create a reflective diary
  • Track
    Automatically track and log every page you have viewed
  • Print
    Print and export a summary to use in your appraisal
Click to find out more »
  • It occurs in about 1 in 1,300 people of Iranian ancestry with Jewish faith. However, it is very rare in those without such ancestry. It has also been reported in Japan. It is inherited as an autosomal recessive disorder and consanguinity is a risk factor.[5] 
  • A seminal paper examined 101 cases in Israel from 1955 to 1969.[2] Of the 101, there were 64 people of Iranian ancestry with Jewish faith and there was a 46% frequency of consanguineous marriage in the parents, compared with 26% amongst people of Iranian ancestry with Jewish faith generally.
  • Although the metabolic defect is present from birth, it rarely presents in infancy and usually becomes apparent in either late teens or early 20s. It has been reported from 10 weeks to around 56 years.
  • Rarely, it may present as cholestasis in neonates.
  • There is recurring jaundice but no pruritus.
  • Despite an equal sex incidence, there is reduced penetrance in females, although it may be precipitated by pregnancy or oral contraceptives due to further inhibition of bilirubin excretion.
  • Clinically there is often nothing to find except for jaundice, although there may be hepatosplenomegaly with palpable organs and a little tenderness.
  • FBC is usually normal as are LFTs with the exception of bilirubin which is elevated.[6] A sulfobromophthalein test will show prolonged retention.
  • The urinary coproporphyrin level is raised with a specific increase in the ratio of coproporphyrin I to coproporphyrin III - a pathognomonic feature of Dubin-Johnson syndrome, as the former is usually excreted in bile and the latter in urine. Prothrombin time may be prolonged, as a subgroup of patients also has a deficiency of factor VII. The two genes may be close together on the number 10 chromosome.
  • Urinary coproporphyrins, excreted as coproporphyrin I, represent 24.8% in those without the gene, 31.6% in heterozygotes and 88.9% in homozygotes. The standard error of the mean was only 1.3%, so it is possible to distinguish heterozygotes with confidence.
  • Laparoscopy examination of the liver will show that it is dark in colour with deposition of a pigment that is rather like melanin.
  • Oral cholecystograms will usually not show the gallbladder. Hepatobiliary radioisotope scans show an intense and prolonged liver image with a very delayed or absent picture of the gallbladder.

Another form of familial hyperbilirubinaemia is Rotor's syndrome but that shows no hyperpigmentation of the liver.[5] The poor or absent imaging of the gallbladder may lead to an erroneous diagnosis of gallstones.

Hyperbilirubinaemia often indicates severe hepatobiliary disease of different causes.[7] Primary biliary cirrhosis causes jaundice and hepatosplenomegaly but there is also marked pruritus and usually positive autoantibodies.

Reassurance is required that no treatment or further investigation is necessary once diagnosis is made. There is no reduction in life expectancy.[3]

Further reading & references

  1. Rastogi A, Krishnani N, Pandey R; Dubin-Johnson syndrome--a clinicopathologic study of twenty cases. Indian J Pathol Microbiol. 2006 Oct;49(4):500-4.
  2. Dubin-Johnson Syndrome, DJS; Online Mendelian Inheritance in Man (OMIM)
  3. Nisa AU, Ahmad Z; Dubin-Johnson syndrome. J Coll Physicians Surg Pak. 2008 Mar;18(3):188-9.
  4. Elferink RO, Groen AK; Genetic defects in hepatobiliary transport. Biochim Biophys Acta. 2002 Mar 16;1586(2):129-45.
  5. Sticova E, Jirsa M; New insights in bilirubin metabolism and their clinical implications. World J Gastroenterol. 2013 Oct 14;19(38):6398-6407.
  6. Giboney PT; Mildly elevated liver transaminase levels in the asymptomatic patient. Am Fam Physician. 2005 Mar 15;71(6):1105-10.
  7. Strassburg CP; Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Best Pract Res Clin Gastroenterol. 2010 Oct;24(5):555-71.

Disclaimer: This article is for information only and should not be used for the diagnosis or treatment of medical conditions. EMIS has used all reasonable care in compiling the information but make no warranty as to its accuracy. Consult a doctor or other health care professional for diagnosis and treatment of medical conditions. For details see our conditions.

Original Author:
Dr Gurvinder Rull
Current Version:
Peer Reviewer:
Dr John Cox
Document ID:
2075 (v22)
Last Checked:
Next Review:

Did you find this health information useful?

Yes No

Thank you for your feedback!

Subcribe to the Patient newsletter for healthcare and news updates.

We would love to hear your feedback!

Patient Access app - find out more Patient facebook page - Like our page