Bilirubin is a breakdown product of red blood cells. Particularly, the haem portion of haemoglobin in the red blood cell after metabolism produces bilirubin. Bilirubin is found along with bile salts and forms bile which is stored in the gallbladder. Bile is released during the process of digestion of fats. Bilirubin as such is water insoluble and is made water soluble by conjugation (conjugated bilirubin) in the liver through biochemical reactions. Increased bilirubin level in the blood causes jaundice or hyperbilirubinemia.
Dubin johnson syndrome (DJS) is an autosomal recessive disorder. Also known as hereditary hyperbilirubinemia ii, chronic idiopathic jaundice and hereditary hyperbilirubinemia. The common feature is chronic and recurrent jaundice without any hepatic injury. Alongside, lipochrome pigmentation is found in the liver. Dubin johnson syndrome usually appears in the second stage of life and is rarely seen in infants.
Causes of dubin-johnson syndrome
Dubin johnson syndrome is caused due to the missense mutation of the ABCC2 gene. The ABCC2 gene produces the protein called MRP2. MRP2 is a transport protein that helps in the excretion of conjugated bilirubin out of the hepatocytes to the bile duct and further removal. When there is a mutation in the ABCC2 gene, the transport protein MRP2 gets defective. Due to the loss of function or decreased production of the transport protein, the conjugated bilirubin within the hepatocytes cannot be transported to the bile duct for excretion. As a result, the bilirubin gets accumulated, particularly conjugated bilirubin. Thus you see a rise in conjugated bilirubin also called direct bilirubin in the blood referred to as conjugated hyperbilirubinemia. At the same time due to the mutation, bilirubin metabolism also gets altered as there is excretion of urinary coproporphyrin.1
Signs and symptoms of dubin-johnson syndrome
Dubin johnson syndrome is an asymptomatic condition, however DJS patients show the following symptoms:
- Conjugated hyperbilirubinemia on routine biochemical testing
- The patient shows symptoms such as lifelong mild jaundice which looks like yellowish sclera and skin
- Upper abdominal pain
- Abnormal urine colour can be seen
Management and treatment for dubin-johnson syndrome
DJS patients have a normal life expectancy and the disorder is mild. Dubin johnson syndrome is a benign disorder and does not require any medical therapy. The treatment is based on the symptoms and supportive treatment is required. However, continuous monitoring of DJS patients is required to prevent hepatobiliary disorders which can lead to hepatic injury.2
Diagnosis of dubin-johnson syndrome
Histological examination via laparoscopy and liver biopsy shows the liver as black in colour. A golden brown pigment (lipochrome) is observed in liver cells. Under light microscopy, a black cast is seen in the centrilobular hepatocytes which is not present in other kinds of hereditary hyperbilirubinemia. These black grainy granules are known to be the deposition of melanin pigment in the liver cell. A liver biopsy is usually not suggested for DJS patients due to its invasive nature. Genetic analysis of the ABCC2 mutation is done in research studies but not for clinical purposes.3
Blood tests, such as a complete blood count, proteins and liver function tests including liver enzymes are required. Laboratory reports show normal liver enzymes, while bile acids are elevated in the blood test. A urine test of DJS patients shows an abnormal ratio of urinary coproporphyrin which is a characteristic feature of dubin johnson syndrome and not observed in other kinds of hereditary hyperbilirubinemia, such as rotor syndrome.
The use of oral contraceptives, alcohol, infection, any other underlying illness and pregnancy can aggrevate the jaundice. These patients are at risk of complications..
Dubin johnson syndrome is a benign condition and does not show any kind of liver disease, such as liver cirrhosis or fibrous progression. However, jaundice and hepatomegaly (enlarged liver) may occur.
Diagnosis of dubin johnson syndrome is complicated and thus requires an interdisciplinary team of doctors. Sometimes the scanning report shows gallstones and arrives at a conclusion of unnecessary removal of the gall bladder.
How can I prevent dubin johnson syndrome?
There is no prevention as such for dubin johnson syndrome as it is a hereditary condition. Genetic counselling may help the parents to arrive at a decision of conceiving an affected baby if the mutation for dubin johnson syndrome runs in the family gene.
How common is dubin johnson syndrome?
Dubin johnson syndrome is a very rare disease and has an equal chance of affecting both people assigned male at birth and people assigned female at birth.
When should I see a doctor?
DJS patients are usually asymptomatic, however, if you experience recurrent jaundice, abdominal pain, or abnormality in urine colour consult a doctor
Dubin johnson syndrome is an autosomal recessive disorder caused by a mutation in the ABCC2 gene. As a result, the transport of bilirubin to the bile duct for excretion through stool does not happen. Therefore the patient suffers with lifelong jaundice. Dubin johnson syndrome is a mild condition and thus the symptoms are not in particular but the common ones are mild abdominal pain and tender liver. Because of the mild nature of the disease, medical therapy is usually not required. Supportive treatment alongside continuous monitoring of the risks can prevent complications of dubin johnson syndrome.
- Junge N, Goldschmidt I, Wiegandt J, Leiskau C, Mutschler F, Laue T, et al. Dubin-johnson syndrome as differential diagnosis for neonatal cholestasis. Journal of Pediatric Gastroenterology and Nutrition [Internet]. 2021 May [cited 2023 May 12];72(5):e105. Available from: https://journals.lww.com/jpgn/Fulltext/2021/05000/Dubin_Johnson_Syndrome_as_Differential_Diagnosis.6.aspx
- Dubin johnson syndrome - symptoms, causes, treatment | nord [Internet]. [cited 2023 May 12]. Available from: https://rarediseases.org/rare-diseases/dubin-johnson-syndrome/
- Talaga ZJ, Vaidya PN. Dubin johnson syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2023 [cited 2023 May 12]. Available from: http://www.ncbi.nlm.nih.gov/books/NBK536994/