Dubin-Johnson syndrome
| Dubin–Johnson syndrome | |
|---|---|
 |
|
| Bilirubin | |
| Classification and external resources | |
| Specialty | endocrinology |
| ICD-10 | E80.6 |
| ICD-9-CM | 277.4 |
| OMIM | 237500 |
| DiseasesDB | 3982 |
| MedlinePlus | 000242 |
| eMedicine | med/588 |
| Patient UK | Dubin–Johnson syndrome |
| MeSH | D007566 |
Dubin–Johnson syndrome (DJS) is a rare, autosomal recessive, benign disorder that causes an isolated increase of conjugated bilirubin in the serum. Classically, the condition causes a black liver due to the deposition of a pigment similar to melanin. This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests. No treatment is usually needed.
The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile. Impaired biliary excretion of bilirubin glucuronides is due to a mutation in the canalicular multiple drug-resistance protein 2 (MRP2). A darkly pigmented liver is due to polymerized epinephrine metabolites, not bilirubin.
DJS is due to a defect in the multiple drug-resistance protein 2 gene (ABCC2), located on chromosome 10. It is an autosomal recessive disease and is likely due to a loss of function mutation, since the mutation affects the cytoplasmic/binding domain.
A hallmark of DJS is the unusual ratio between the byproducts of heme biosynthesis:
In post mortem autopsy, the liver will have a dark pink or black appearance due to pigment accumulation.
Plentiful canalicular multiple drug-resistant protein 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. High levels of gamma-glutamyl transferase (GGT) help in diagnosing pathologies involving biliary obstruction.
Dubin–Johnson syndrome is similar to Rotor syndrome, but can be differentiated by:
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