Dubin-Johnson syndrome is an autosomal recessive disorder which causes an increase of conjugated bilirubin without elevation of liver enzymes (ALT, AST). This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. It is usually asymptomatic but may be diagnosed in early infancy based on laboratory tests.
A hallmark of DJS is the unusual ratio between the byproducts of heme biosynthesis. Unaffected subjects have a coproporphyrin III to coproporphyrin I ratio of approximately 3-4:1. In patients with DJS, this ratio is inverted with coproporphyrin I being 3-4x higher than coproporphyrin III. Analysis of urine porphyrins show a normal level of coproporphyrin but the I isomer accounts for 80% of the total (normally 25%). In post-mortem autopsy, the liver will have a dark pink or black appearance due to pigment accumulation.
There is plenty of canalicular multi-drug resistant protein which causes bilirubin transfer to bile canaliculi. An isoform of this protein is localized to the apical hepatocyte membrane, allowing transport of glucuronide and glutathione conjugates back into the blood.
DJS is due to a defect in the multispecific anion transporter (cMOAT) gene (ABC transporter superfamily). It is an autosomal recessive disease and is likely due to a loss of function mutation, since the mutation affects the cytoplasmic / binding domain.