Dubin–Johnson syndrome

Overview

Dubin–Johnson syndrome is a rare, inherited liver disorder characterized by chronic conjugated hyperbilirubinemia, meaning elevated levels of direct (conjugated) bilirubin in the blood. Despite this abnormality, liver function remains largely normal, and affected individuals often have few or no symptoms. The condition is usually benign and discovered incidentally during liver function tests or evaluations for jaundice. A distinguishing feature of Dubin–Johnson syndrome is the dark pigmentation of the liver due to pigment accumulation.

Causes

Dubin–Johnson syndrome is caused by mutations in the ABCC2 gene, which encodes the MRP2 (multidrug resistance-associated protein 2) transporter. This protein is responsible for transporting conjugated bilirubin and other organic compounds from liver cells into bile for excretion. When MRP2 is defective, bilirubin builds up in liver cells and eventually leaks into the bloodstream, resulting in elevated conjugated bilirubin levels.

The disorder is inherited in an autosomal recessive pattern, meaning a person must inherit one defective copy of the gene from each parent to be affected.

Symptoms

Most individuals with Dubin–Johnson syndrome are asymptomatic or have very mild symptoms. When present, symptoms may include:

• Intermittent jaundice: Yellowing of the skin and eyes, often triggered by illness, pregnancy, oral contraceptives, or stress.

• Dark-colored urine: Due to increased bilirubin excretion in the urine.

• Mild fatigue or abdominal discomfort: Occasionally reported, though not common.

Importantly, individuals with this condition do not typically experience pruritus (itching), which is common in other cholestatic liver diseases.

Diagnosis

Diagnosis of Dubin–Johnson syndrome is based on a combination of clinical findings, laboratory tests, and imaging. Diagnostic steps include:

• Liver function tests: Show isolated elevation of conjugated bilirubin with otherwise normal liver enzymes (ALT, AST, ALP).

• Urinary coproporphyrin test: Elevated total coproporphyrins with a characteristic reversal of isomer ratio (increased isomer I vs. isomer III).

• Liver biopsy: May reveal dark, pigmented granules in liver cells (though usually not required for diagnosis).

• Imaging (e.g., HIDA scan): May show delayed biliary excretion.

• Genetic testing: Can confirm mutations in the ABCC2 gene.

It is important to distinguish Dubin–Johnson syndrome from other causes of jaundice and liver dysfunction, such as Rotor syndrome or hepatobiliary diseases.

Treatment

There is no specific treatment required for Dubin–Johnson syndrome, as it is a benign condition. Management focuses on reassurance and avoiding triggers that may exacerbate jaundice. Recommendations include:

• Avoid hepatotoxic drugs or substances that place extra stress on the liver.

• Monitor during pregnancy: Jaundice may worsen during pregnancy, but this typically resolves after delivery.

• Regular follow-up: Not usually necessary unless new symptoms develop or for differential diagnosis in unclear cases.

Since liver function is preserved, no liver-directed therapy is needed, and dietary restrictions are not required.

Prognosis

The prognosis for Dubin–Johnson syndrome is excellent. It does not lead to liver damage, cirrhosis, or liver failure. Affected individuals can lead normal, healthy lives with a normal life expectancy. The primary concern is differentiating it from more serious liver conditions to prevent unnecessary testing or treatment. Once diagnosed, patient education and reassurance are typically sufficient for long-term care.