Dubin–Johnson syndrome

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Dubin–Johnson syndrome
Classification and external resources
Bilirubin.svg
ICD-10 E80.6
ICD-9 277.4
OMIM 237500
DiseasesDB 3982
MedlinePlus 000242
eMedicine med/588
Patient UK Dubin–Johnson syndrome
MeSH D007566

Dubin–Johnson syndrome (DJS) is an autosomal recessive disorder that causes an increase of conjugated bilirubin in the serum 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, and is similar to Rotor syndrome. It is usually asymptomatic, but may be diagnosed in early infancy based on laboratory tests.

Pathophysiology[edit]

The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile.[1] 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.[2]

Diagnosis[edit]

A hallmark of DJS is the unusual ratio between the byproducts of heme biosynthesis:

  • Unaffected subjects have a coproporphyrin III to coproporphyrin I ratio around 3–4:1.
  • In patients with DJS, this ratio is inverted, with coproporphyrin I being 3–4 times higher than coproporphyrin III. Analysis of urine porphyrins shows 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.

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:

Rotor syndrome Dubin–Johnson syndrome
appearance of liver normal histology and appearance liver has black pigmentation
gallbladder visualization gallbladder can be visualized by oral cholecystogram gallbladder cannot be visualized
total urine coproporphyrin content high with <70% being isomer 1 normal with >80% being isomer 1 (normal urine contains more of isomer 3 than isomer 1)

Genetics[edit]

Dubin–Johnson syndrome has an autosomal recessive pattern of inheritance.

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.

Prognosis[edit]

Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are asymptomatic and have normal lifespans.[1] Some neonates present with cholestasis.[1] Hormonal contraceptives and pregnancy may lead to overt jaundice and icterus (yellowing of the eyes and skin).

See also[edit]

References[edit]

  1. ^ a b c Suzanne M Carter, MS Dubin–Johnson Syndrome at eMedicine
  2. ^ Kumar, Vinay (2007). Robbins Basic Pathology. Elsevier. p. 639. 

External links[edit]

Dubin-Johnson syndrome at New York Times

Dubin-Johnson syndrome at ght.nlm.nig.gov

Dubin-Johnson syndrome at Medline Plus encyclopedia

Dubin–Johnson syndrome at NIH's Office of Rare Diseases