Dubin-johnson syndrome E80.6

IN Dubin and FB Johnson 1954

Benign, autosomal recessive hereditary with nonpruritic hyperbilirubinemia, caused by an excretion disorder of the bilirubin (conjugation is normal - see laboratory below) of the adolescent or early adult.

Can be proven in all ethnic groups. More common among Iranian and Moroccan Jews (Shani M et al. 1970).

Caused by autosomal recessively inherited homozygous mutations in the Canalicular multispecific organic anion transporter gene also called CMOAT gene (or ATP-binding cassette subfamily C member 2 gene; ABCC2) which is located on chromosome 10q24. The ABCC2 gene codes for an ATP-dependent transporter in the apical membrane (multidrug resistance-associated protein 2 - MRP2) which enables the efflux of glucuronated bilirubin and other organic anions from the liver cell into the bile ducts.

Adolescence, Adulthood

Patients become conspicuous in adolescence or early adulthood by a mild to moderate non pruritic jaundice. Frequently intercurrent infections, pregnancy (Gupta A et al. 2019) are the triggering factors. Also oral contraceptives or medication. During the episodes there is sometimes abdominal pain and fatigue, in rare cases hepatosplenomegaly develops.

Ultrasound findings of the liver: unremarkable

Diagnostically useful may also be the 99mTc HIDA cholinescintigraphy, in which the gallbladder and bile ducts are visualized delayed or not at all, while the liver remains visible for a prolonged time.

Total serum bilirubin (50-80% detectable as conjugated bilirubin) moderately increased (2.0-5.0 mg/dl, very rarely higher. Liver enzymes (aminotransferases, alkaline phosphatase, gamma-glutamyl-transpeptidase), albumin level and prothrombin time: normal.

Especially in the population of Iranian and Moroccan Jews an association with coagulation factor VII deficiency can be observed.

Detection of a characteristic coproporphyrin excretion pattern (normal concentration of total coproporphyrin when the proportion of coproporphyrin-1 is increased to more than 80%).

Black-brown, melanin-like pigment deposits in the hepatocytes, mainly in the centrilobular area. No further histological changes.

Detection of mutations in the ABCC2 gene. liver biopsy.

• Gilbert-Meulengracht disease
• Crigler-Najjar syndrome
• Rotor syndrome
• Hepatitis
• Hemolysis
• Malformations of the bile ducts

A curative therapy is not known. Phenobarbital led in some cases to a decrease in serum bilirubin levels.

No signs of progression. No evidence of the development of liver insufficiency, cirrhosis or fibrosis.

1. Gupta A et al (2019) A Case of Dubin-Johnson Syndrome in Pregnancy. Cureus 11:e4048.
2. Kularatnam GAM et al (2017) Dubin-Johnson syndrome and intrahepatic cholestasis of pregnancy in a Sri Lankan family: a case report. BMC Res Notes 10:487.
3. Shani M et al (1970) Dubin-Johnson syndrome in Israel. I. Clinical, laboratory, and genetic aspects of 101 cases. Quart J Med 39: 549-567
4. Strasbourg CP (2010) Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndromes). Best Pract Res Clin Gastroenterol 24:555-571.