Dubin-Johnson Syndrome

Synonyms: Hyperbilirubinaemia II, DJS, Sprinz-Nelson syndrome

This is a rare inherited disorder of bilirubin metabolism that was described by Dubin and Johnson in 1954 and independently by Sprinz and Nelson.¹ There is no haemolysis but conjugated bilirubin is raised due to a defect on the chromosome 10q24 affecting the multispecific anion transporter (cMOAT) protein. 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.² It runs a generally benign course.

• It occurs in about 1 in 1300 Iranian Jews but is very rare in those without such ancestry. It has also been reported in Japan. It is inherited as an autosomal recessive and consanguinity is a risk factor.
• A seminal paper examined 101 cases in Israel from 1955 to 1969.¹ Of the 101, there were 64 Iranian Jews and there was a 46% frequency of consanguineous marriage in the parents, compared with 26% amongst Iranian Jews 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.³
• 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.^4,5
• 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 sulphobromophthalein 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 DJS as the former is usually excreted in bile and the latter in urine. Prothrombin time may be prolonged as a subgroup of patients also have a deficiency of factor VII. The 2 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 gall bladder. 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 syndrome but that shows no hyperpigmentation of the liver. The poor or absent imaging of the gall bladder may lead to an erroneous diagnosis of gallstones. Primary biliary cirrhosis causes jaundice and hepatosplenomegaly but there is marked pruritus.

Reassurance is required that no treatment is necessary, nor further investigation, once diagnosis is made. There is no reduction in life expectancy.