Dubin Johnson Syndrome

Pathophysiology

1) decreased intracellular transport of conjugated bilirubin 2) cause is defective hepatocellular secretion of bilirubin glucuronides into the canalicular lumen

Signs and Symptoms

1) fairly benign clincially 2) mild, episodic jaundice 3) vague complaints of weakness and fatigue 4) some cases with hepatomegaly 5) 50% of patients have dark-colored urine 6) often does not present until first pregnancy or use of oral contraceptives

Characteristic Test Findings

Laboratory – 1) chronically elevated, fluctuating levels of conjugated bilirubin (2-5 mg/dL) 2) bilirubinuria (bilirubin in the urine) 3) total amount of serum coproporphyrins is normal, but the fraction of the type 1 isomer is increased from 25% to 80%

Histology/Gross Pathology

1) brownish pigment deposition in hepatocyte centrilobular zone and Kupffer cells 2) grossly, the liver looks black

Biochemistry

1) specific defect is in ATP-dependent transport mechanism of bilirubin glucuronides into the canaliculus 2) caused by point mutation in multi-drug resistance-associated protein 2 (MRP2) 3) defect also exists in transport of coproporphyrins

Inheritance/Epidemiology

1) autosomal recessive 2) rare 3) tends to occur most commonly in groups with high rates of intermarriage such as Iranian Jews and remote island populations

Tips for USMLE

1) study of the urinary coproporphyrin level is used to distinguish Dubin-Johnson from other conjugated hyperbilirubinemias 2) in most liver diseases with jaundice, the total coproporphyrin is elevated with type 1 isomer no more than 65%