What is Dubin-Johnson Syndrome?
In 1954, Dubin and Johnson identified a new medical condition involving chronic unexplained yellowing of the skin (jaundice) coupled with an unknown pigment in the liver. The same year, Sprinz and Nelson reported on four similar cases, and this condition soon became known as Dubin Johnson syndrome (DJS). This rare inherited disorder causes a slight increase in the levels of a certain type of bilirubin (a substance normally processed by the liver) in the blood, but without any other indicators of liver damage. This happens due to a genetic mutation that affects how bilirubin is removed from liver cells.
DJS usually first appears in adolescents but can occasionally develop in infants as well. Despite this, it’s a harmless disorder that doesn’t have any long-term effects or require any medical treatment. However, it’s important to diagnose DJS to rule out other liver and bile duct diseases that can cause liver damage and identify any that might be potentially treatable.
What Causes Dubin-Johnson Syndrome?
Dubin-Johnson Syndrome, or DJS, is caused by changes in a gene called the ATP binding cassette subfamily C member (ABCC2) gene. This gene is responsible for creating a protein known as the multidrug resistance protein 2 (MRP2), which acts like a transportation service within our cells.
MRP2 plays an important role in moving substances out of cells. It is particularly crucial for moving a substance known as conjugated bilirubin from the cells in the liver to the bile duct system, where it can be removed from the body.
If there is a mutation in the ABCC2 gene, the MRP2 protein cannot function properly. This means it can’t move the conjugated bilirubin out of the liver cells into the bile duct as usual. As a result, conjugated bilirubin builds up in the liver cells and increases in the blood.
Another characteristic of DJS is a shift in the balance of two byproducts created during a process called heme synthesis. The amounts of a byproduct called urinary coproporphyrin I are higher than another byproduct called coproporphyrin lll. Usually, in healthy people, the ratio of coproporphyrin lll to coproporphyrin I is roughly 3.5:1.
Risk Factors and Frequency for Dubin-Johnson Syndrome
DJS, a rare disorder, affects both men and women and usually develops during adolescence or early adulthood. The condition is present in every race and nationality, but it’s seen more often in Sephardic Jews. Interestingly, while the disorder impacts both sexes, it tends to start earlier in males and usually isn’t found in children under ten.
Signs and Symptoms of Dubin-Johnson Syndrome
Dubin-Johnson syndrome (DJS) often affects young adults and is usually without noticeable symptoms. It is generally discovered when increased levels of bilirubin (hyperbilirubinemia) are found in blood tests conducted for other reasons. Infrequently, symptoms such as mild jaundice (yellowing of the skin and eyes), weakness, and upper abdominal discomfort can occur. It’s important to note that itching (pruritus) is not a symptom of DJS since the levels of bile acids in the blood are normal.
In women, DJS may go unnoticed until they begin using oral contraceptives or become pregnant. During these times, high bilirubin levels or visible jaundice can lead to the diagnosis of DJS. Other than mild jaundice, physical check-ups usually show normal results.
Testing for Dubin-Johnson Syndrome
People with Dubin-Johnson Syndrome (DJS) often have increased levels of bilirubin, a yellowish substance in your blood that forms after red blood cells break down. This is known as hyperbilirubinemia, and it’s mainly linked to what’s called conjugated hyperbilirubinemia. Typically, bilirubin levels for these patients fall between 2 and 5 mg/dL, but rarely, they may rise to 20-25 mg/dL.
Even though they have high bilirubin levels, these patients usually have normal results on other lab tests, such as complete blood count, serum albumin, and liver enzymes. Importantly, there’s no sign of red blood cells breaking down too quickly, called hemolysis.
A particular hallmark of DJS is an abnormality in urinary coproporphyrin excretion. Coproporphyrin, a waste product of red blood cells, exists as isomers I and III. In a normal situation, about 75% of the coproporphyrin in urine is isomer III. In DJS patients, the total coproporphyrin content in the urine is normal, but more than 80% is isomer I.
In some cases, imaging tests like the hepatobiliary iminodiacetic acid (HIDA) scan or a CT scan of the abdomen might be performed. For DJS patients, the HIDA scan might show a particular pattern of delayed or even no visibility of the gallbladder and bile ducts, despite the liver being clearly visible. Similarly, a CT scan in patients with DJS might show different results compared to healthy individuals. Yet, these imaging studies are often not required if DJS is suspected.
An older test, known as the Bromosulphthaleine (BSP) clearance test, isn’t commonly used today. But if it were done on someone with DJS, the results would show a particular pattern, with a second peak occurring at 90 minutes, indicating a defect in excretion.
A liver biopsy in DJS might show the build-up of a dark, granular pigment in certain cells in the liver. However, the liver itself will look normal and this test isn’t recommended for diagnosing DJS.
The diagnosis of DJS is mostly based on high bilirubin levels, with normal liver function tests and elevated urinary coproporphyrin I. Invasive diagnostic tests are usually avoided. Although there’s a gene test for DJS (genotyping the ABCC2 gene), this is mainly used for research, not clinical purposes.
Treatment Options for Dubin-Johnson Syndrome
DJS, also known as Dubin-Johnson Syndrome, is a harmless condition. It doesn’t get worse over time, nor does it lead to scarring or cirrhosis of the liver. This means it generally doesn’t need any treatment. However, it’s important to diagnose DJS to rule out other liver and bile duct disorders that could harm the liver and those that can be potentially treatable. In severe cases of neonatal DJS, where there’s a blockage in the flow of bile, medications like Phenobarbital and Ursodeoxycholic acid can be used as treatment.
What else can Dubin-Johnson Syndrome be?
When trying to identify the cause of a particular medical condition, doctors consider a range of potential diagnoses. These may include:
- Blockages in the bile duct
- Liver conditions that prevent proper bile flow
- Acute or long-lasting liver damage
- Rotor syndrome – a rare genetic disorder affecting liver function
- Conditions that destroy red blood cells (Hemolysis) or other blood diseases
- Abnormal connections between the liver’s blood vessels (Portosystemic shunting)
- Gilbert-Meulengracht syndrome – a mild liver disorder causing occasional jaundice
- Crigler-Najjar syndrome – a rare genetic disorder causing high levels of bilirubin, a substance that the liver produces and turns into bile
- Jaundice caused by breastfeeding – a common and usually harmless condition in newborns, where the milk can sometimes make the skin look yellow (Breast milk Jaundice)
The above possibilities are considered and examined through appropriate tests to confirm the exact issue and offer the best treatment.
What to expect with Dubin-Johnson Syndrome
The outlook for DJS is often positive, and it typically doesn’t affect a person’s lifespan.
Possible Complications When Diagnosed with Dubin-Johnson Syndrome
Dubin-Johnson Syndrome (DJS) does not increase the risk of developing fibrosis or cirrhosis, which are toughening and scarring conditions of the liver. However, individuals with DJS may experience yellowing of the skin and eyes, known as jaundice, and an enlargement of the liver, called hepatomegaly. Certain circumstances such as taking oral contraceptives, experiencing another sickness, or being pregnant can trigger jaundice.
Preventing Dubin-Johnson Syndrome
Patients can be informed about the harmless nature of Dubin-Johnson syndrome (DJS), and that it is important to diagnose it properly to rule out other conditions that might cause liver damage.