Dubin-Johnson syndrome

Dubin-Johnson syndrome (DJS), also known as Dubin-Johnson hyperbilirubinemia, is a rare, benign inherited liver disorder characterized by chronic or intermittent conjugated (direct) hyperbilirubinemia. The condition is caused by mutations in the ABCC2 gene (also known as MRP2), which encodes a canalicular multispecific organic anion transporter protein responsible for excreting conjugated bilirubin and other organic anions from hepatocytes into bile. When this transporter is deficient or dysfunctional, conjugated bilirubin accumulates in the blood, leading to the hallmark symptom of intermittent jaundice — a yellowing of the skin and whites of the eyes. The liver in Dubin-Johnson syndrome characteristically appears grossly black or dark brown due to the accumulation of a melanin-like pigment within hepatocytes, which is a distinctive pathological finding. Despite this pigment deposition, liver function remains essentially normal, and the condition is considered benign with an excellent prognosis and normal life expectancy. Jaundice may be exacerbated by intercurrent illness, oral contraceptive use, pregnancy, or other stressors. Some patients may experience mild hepatomegaly, vague abdominal pain, or fatigue, though many individuals remain entirely asymptomatic aside from jaundice. Laboratory findings include elevated conjugated bilirubin, a characteristic pattern on urinary coproporphyrin analysis (with a reversal of the normal coproporphyrin I to coproporphyrin III ratio), and delayed visualization or non-visualization of the gallbladder on oral cholecystography or hepatobiliary scintigraphy. No specific treatment is required for Dubin-Johnson syndrome, as the condition is benign and does not progress to liver failure or cirrhosis. Management focuses on reassurance, avoidance of exacerbating factors such as estrogen-containing medications when possible, and genetic counseling for affected families. The syndrome is more prevalent in certain populations, notably Iranian and Moroccan Jews, where carrier frequencies are higher. Diagnosis is typically confirmed through clinical findings, characteristic coproporphyrin excretion patterns, and, when necessary, genetic testing of the ABCC2 gene or liver biopsy demonstrating the pathognomonic dark pigment.

Common questions about Dubin-Johnson syndrome