Dubin-Johnson syndrome

From Ask Dr Wiki

{{#if:|

}}

 | 

   | serious  = Image:Stop hand nuvola.svg
   | content  = Image:Emblem-important.svg
   | style    = Image:Broom icon.svg
   | merge    = Image:Merge-split-transwiki default.svg
   | notice   = Image:Info non-talk.png
   | blank    = Image:No image.svg
   | #default = none

Dubin-Johnson syndrome is an autosomal recessive disorder which causes an increase of conjugated bilirubin without elevation of liver enzymes (ALT, AST). It is usually diagnosed in early infancy.

Diagnosis

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 lateral hepatocyte membrane, allowing transport of glucuronide and glutathione conjugates back into the blood.

Analysis of urine porphyrins show a normal level of coproporphyrin but the I isomer accounts for 80% of the total (normally 25%)

Liver will present with dark pink or black appearance due to pigment accumulation.

The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile.^[1] Pigment deposition in lysosomes causes the liver to turn black. 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 III being 3-4x higher then coproporphyrin I.

Genetics

DJS has a defect in the multispecific anion transporter (cMOAT) gene (ABC transporter superfamily). Likely a loss of function mutation, since the mutation affects the cytoplasmic / binding domain.

Prognosis

Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are asymptomatic and have normal life spans.^[1] Some neonates will present with cholestasis.^[1]

Oral contraceptive and pregnancy may lead to overt jaundice and icterus (yellowing of the eyes)

References

1. ↑ ^{1.0 1.1 1.2} Suzanne M Carter, MS. eMedicine: Dubin-Johnson Syndrome. January 9, 2007. http://www.emedicine.com/ped/topic621.htm

See also

• Jaundice
• Gilbert syndrome
• Crigler-Najjar syndrome
• Rotor syndrome

Template:Genetic-disorder-stub

pl:Zespół Dubina-Johnsona