Dubin–Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

 in the serum without elevation of liver

Liver

The liver is a vital organ present in vertebrates and some other animals. It has a wide range of functions, including detoxification, protein synthesis, and production of biochemicals necessary for digestion...

 enzymes (ALT

Alanine transaminase

Alanine transaminase or ALT is a transaminase enzyme . It is also called serum glutamic pyruvic transaminase or alanine aminotransferase ....

, AST

Aspartate transaminase

Aspartate transaminase , also called aspartate aminotransferase or serum glutamic oxaloacetic transaminase , is a pyridoxal phosphate -dependent transaminase enzyme . AST catalyzes the reversible transfer of an α-amino group between aspartate and glutamate and, as such, is an important enzyme in...

). This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin

Bilirubin

Bilirubin is the yellow breakdown product of normal heme catabolism. Heme is found in hemoglobin, a principal component of red blood cells. Bilirubin is excreted in bile and urine, and elevated levels may indicate certain diseases...

 into the bile, and is similar to Rotor syndrome

Rotor syndrome

Rotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder of unknown origin...

. It is usually asymptomatic but may be diagnosed in early infancy based on laboratory tests.

Pathophysiology

The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile. Pigment deposition in lysosomes causes the liver to turn black.

Diagnosis

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 porphyrin
  Porphyrin
  Porphyrins are a group of organic compounds, many naturally occurring. One of the best-known porphyrins is heme, the pigment in red blood cells; heme is a cofactor of the protein hemoglobin. Porphyrins are heterocyclic macrocycles composed of four modified pyrrole subunits interconnected at...
  
  s show a normal level of coproporphyrin but the I isomer accounts for 80% of the total (normally 25%).

In post-mortem autopsy

Autopsy

An autopsy—also known as a post-mortem examination, necropsy , autopsia cadaverum, or obduction—is a highly specialized surgical procedure that consists of a thorough examination of a corpse to determine the cause and manner of death and to evaluate any disease or injury that may be present...

, the liver will have a dark pink or black appearance due to pigment

Pigment

A pigment is a material that changes the color of reflected or transmitted light as the result of wavelength-selective absorption. This physical process differs from fluorescence, phosphorescence, and other forms of luminescence, in which a material emits light.Many materials selectively absorb...

 accumulation.

There is plenty of canalicular multi-drug resistant protein that causes bilirubin transfer to bile canaliculi. An isoform of this protein is localized to the apical hepatocyte membrane, allowing transport of glucuronide

Glucuronide

A glucuronide, also known as glucuronoside, is any substance produced by linking glucuronic acid to another substance via a glycosidic bond...

 and glutathione

Glutathione

Glutathione is a tripeptide that contains an unusual peptide linkage between the amine group of cysteine and the carboxyl group of the glutamate side-chain...

 conjugates back into the blood.

High levels of gamma-glutamyl transferase (GGT) help in diagnosing pathologies involving biliary obstruction.

Genetics

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

Prognosis is good, and treatment of this syndrome is usually unnecessary. Most patients are asymptomatic and have normal life spans. Some neonates will present with cholestasis. Hormonal contraceptives and pregnancy

Pregnancy

Pregnancy refers to the fertilization and development of one or more offspring, known as a fetus or embryo, in a woman's uterus. In a pregnancy, there can be multiple gestations, as in the case of twins or triplets...

 may lead to overt jaundice and icterus (yellowing of the eyes and skin).

See also

• Jaundice
  Jaundice
  Jaundice is a yellowish pigmentation of the skin, the conjunctival membranes over the sclerae , and other mucous membranes caused by hyperbilirubinemia . This hyperbilirubinemia subsequently causes increased levels of bilirubin in the extracellular fluid...
  
  
• Gilbert syndrome
• Crigler-Najjar syndrome
  Crigler-Najjar syndrome
  Crigler-Najjar Syndrome or CNS is a rare disorder affecting the metabolism of bilirubin, a chemical formed from the breakdown of blood. The disorder results in an inherited form of non-hemolytic jaundice, which results in high levels of unconjugated bilirubin and often leads to brain damage in...
  
  
• Rotor syndrome
  Rotor syndrome
  Rotor syndrome, also called Rotor type hyperbilirubinemia, is a rare, relatively benign autosomal recessive bilirubin disorder of unknown origin...