Dubin Johnson Syndrome

Dubin Johnson syndrome is a benign autosomal recessive disorder of canalicular excretion of conjugated bilirubin due to mutation in ABCC2 (MRP2).

• Prevalence about 1 in 1,300 among Iranian Jews, rare elsewhere.
• Conjugated hyperbilirubinaemia with a normal liver otherwise, and characteristic black pigmented liver (epinephrine metabolite pigment in lysosomes).
• Hepatic bile salt excretion is normal, so there is no pruritus or pale stools.
• Life expectancy is normal. Jaundice is exacerbated by pregnancy, oral contraceptives, infection and alcohol.

• Mild chronic or intermittent jaundice, often from adolescence or early adulthood, with fatigue or vague abdominal discomfort.
• Dark urine, normal stools, no pruritus.
• Hepatomegaly is uncommon. Examination otherwise normal.
• Neonatal cholestasis can occur (rare, cholestatic presentation).

• Conjugated hyperbilirubinaemia (total bilirubin 2 to 5 mg/dL, up to 20), with direct fraction over 50%; other liver tests normal.
• Urinary coproporphyrin: total normal, with over 80% as isomer I (normally 25%).
• Oral cholecystography does not visualise the gallbladder; HIDA scan shows delayed biliary excretion with prominent hepatic retention.
• Liver biopsy: coarse brown black pigment in centrilobular hepatocytes; normal architecture (not needed).
• ABCC2 genetic testing. Exclude Rotor syndrome (no pigment), obstruction, hepatitis, drug induced cholestasis.

• No treatment is needed. Reassurance and genetic counselling.
• Avoid oestrogen containing contraceptives, which worsen jaundice. Use alternatives.
• Phenobarbital does not lower bilirubin and is not indicated.
• Pregnancy is generally safe, with transient jaundice.
• Drug awareness: reduced excretion of methotrexate and some drugs transported by MRP2; dose adjustment may be required.
• Warn the patient about benign nature to avoid unnecessary surgery and investigation, and carry diagnostic documentation.
• Follow up is not required.