Which are the causes of Dubin-Johnson syndrome?

Dubin-Johnson syndrome is a rare genetic disorder that affects the liver's ability to process and excrete bilirubin, a yellow pigment produced during the breakdown of red blood cells. This condition is characterized by a buildup of bilirubin in the liver cells, leading to its accumulation in the bloodstream and subsequent jaundice.

Causes:

The primary cause of Dubin-Johnson syndrome is a mutation in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene. This gene provides instructions for producing a protein that is responsible for transporting bilirubin out of liver cells and into the bile, a fluid that aids in digestion. When the ABCC2 gene is mutated, the MRP2 protein is either absent or dysfunctional, resulting in impaired bilirubin transport.

Inheritance:

Dubin-Johnson syndrome follows an autosomal recessive pattern of inheritance, meaning that an individual must inherit two copies of the mutated ABCC2 gene (one from each parent) to develop the condition. If both parents carry a single copy of the mutated gene, they are considered carriers and have a 25% chance of having an affected child with each pregnancy.

Genetic Mutations:

Several different mutations in the ABCC2 gene have been identified in individuals with Dubin-Johnson syndrome. These mutations can vary in their severity and impact on the function of the MRP2 protein. Some mutations completely disrupt the production of the protein, while others result in a partially functional protein. The specific mutation present in an individual can influence the severity of the symptoms experienced.

Impaired Bilirubin Transport:

The MRP2 protein plays a crucial role in the transport of bilirubin from liver cells into the bile. In individuals with Dubin-Johnson syndrome, the impaired function of this protein leads to a reduced ability to excrete bilirubin. As a result, bilirubin accumulates in the liver cells and spills over into the bloodstream, causing jaundice.

Other Factors:

While the primary cause of Dubin-Johnson syndrome is the genetic mutation in the ABCC2 gene, other factors may influence the severity and presentation of the condition. Hormonal changes, such as those occurring during pregnancy or with the use of oral contraceptives, can exacerbate the symptoms of jaundice. Additionally, certain medications, such as anabolic steroids and some antibiotics, have been reported to worsen the condition in individuals with Dubin-Johnson syndrome.

Conclusion:

Dubin-Johnson syndrome is primarily caused by mutations in the ABCC2 gene, leading to impaired bilirubin transport and subsequent jaundice. The condition follows an autosomal recessive pattern of inheritance and can vary in severity depending on the specific mutation present. While the genetic mutation is the main cause, hormonal changes and certain medications can also impact the symptoms experienced by individuals with Dubin-Johnson syndrome.