Dubin-Johnson syndrome

What it is, symptoms and effects

From: MedlinePlus Genetics, National Library of Medicine

Dubin-Johnson syndrome is a condition characterized by jaundice, which is a yellowing of the skin and whites of the eyes. In most affected people jaundice appears during adolescence or early adulthood. Jaundice is typically the only feature of Dubin-Johnson syndrome, but some people can experience weakness, mild abdominal pain, nausea, or vomiting. In most people with Dubin-Johnson syndrome, certain deposits build up in the liver but do not seem to impair liver function. The deposits make the liver appear black when viewed with medical imaging.

Rarely, jaundice develops soon after birth in individuals with Dubin-Johnson syndrome. Affected infants typically also have enlarged livers (hepatomegaly) and a severely reduced ability to produce and release a digestive fluid called bile (cholestasis). As these children get older, their liver problems go away and they usually do not have any related health problems later in life.

Causes and biological mechanisms

From: MedlinePlus Genetics, National Library of Medicine

Dubin-Johnson syndrome is caused by changes in a gene known as ABCC2. The ABCC2 gene provides instructions for making a protein that transports certain substances out of cells so they can be released (excreted) from the body. For example, this protein transports a substance called bilirubin out of liver cells and into bile (a digestive fluid produced by the liver). Bilirubin is produced during the breakdown of old red blood cells and has an orange-yellow tint.

ABCC2 gene mutations result in the production of a protein with reduced or absent activity that cannot effectively transport substances out of cells. These mutations particularly affect moving bilirubin into bile. As a result, bilirubin accumulates in the body, causing a condition called hyperbilirubinemia. The buildup of bilirubin in the body causes the yellowing of the skin and whites of the eyes in people with Dubin-Johnson syndrome. The black liver in affected individuals is due to a buildup of different substance normally transported out of the liver by the protein produced from the ABCC2 gene.

Inheritance and family implications

From: MedlinePlus Genetics, National Library of Medicine

This condition is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have mutations. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.

How common is it?

From: MedlinePlus Genetics, National Library of Medicine

The prevalence of Dubin-Johnson syndrome is unknown. It appears to be most common in Iranian and Moroccan Jews living in Israel, with 1 in 1,300 individuals affected. Additionally, several people in the Japanese population have been diagnosed with Dubin-Johnson syndrome. This condition appears to be less common in other populations.

Reported clinical features and what the terms mean

The following findings are associated with this condition in Orphanet. They are not a checklist for diagnosing yourself, and they do not all occur in every affected person. Some are examination, imaging or laboratory findings that cannot be recognised at home.

The frequency labels describe how often a finding was reported among people with the condition in the source. They do not give the chance that a person with that symptom has the condition. Definitions below reproduce HPO terminology; they explain the term, not the likely severity in an individual.

Abnormal urinary color · Very frequent (99-80%)

An abnormal color of the urine, that is, the color of the urine appears different from the usual straw-yellow color.

Abnormality of the liver · Very frequent (99-80%)

An abnormality of the liver.

Biliary tract abnormality · Very frequent (99-80%)

An abnormality of the biliary tree.

Jaundice · Very frequent (99-80%)

Yellow pigmentation of the skin due to bilirubin, which in turn is the result of increased bilirubin concentration in the bloodstream.

Conjugated hyperbilirubinemia · Very frequent (99-80%)

Abnormality of the gastric mucosa · Frequent (79-30%)

An abnormality of the gastric mucous membrane.

Abdominal pain · Occasional (29-5%)

An unpleasant sensation characterized by physical discomfort (such as pricking, throbbing, or aching) and perceived to originate in the abdomen.

Abnormality of coagulation · Occasional (29-5%)

An abnormality of the process of blood coagulation. That is, altered ability or inability of the blood to clot.

Fatigue · Occasional (29-5%)

A subjective feeling of tiredness characterized by a lack of energy and motivation.

Fever · Occasional (29-5%)

Body temperature elevated above the normal range.

Hepatomegaly · Occasional (29-5%)

Abnormally increased size of the liver.

Which doctor should you see?

The suggested department for discussing Dubin-Johnson syndrome is Hepatology, with a hepatologist / gastroenterologist as the relevant type of clinician. General physician / Family Medicine; paediatrician for children. Referral depends on symptoms.

Additional services that may be relevant, depending on the findings, include: Clinical Genetics.

This is an editorial referral starting point. The appropriate clinic depends on the person’s age, symptoms, previous diagnosis and local services. The first clinician can decide whether another specialty or a team is needed; a department label does not confirm the diagnosis.

How to prepare for an assessment

Bring a short timeline of the main symptoms: when they first appeared, whether they are constant or episodic, what seems to change them, and how they affect daily activities. Include previous reports, discharge summaries, current medicines and supplements, allergies, and any relevant family history. A dated record is more useful than trying to match every feature in an online article.

Ask the clinician what is already established and what remains uncertain. If a test is suggested, ask what question it answers, what its limitations are and how the result would change the next step. The information here is not an instruction to arrange every possible test. In children, bring growth, developmental and school information if it is relevant to the concern.

• What is known about the cause and extent of liver involvement?
• Which medicines, supplements or exposures should be reviewed?
• What follow-up is appropriate for the specific diagnosis and stage?

Treatment discussions and follow-up

The material gathered for this draft does not provide a complete condition-specific treatment pathway for Dubin-Johnson syndrome. That gap does not mean that treatment is unavailable. A clinician needs to establish the diagnosis and review current guidance before recommending medicines, procedures, rehabilitation or other support.

Before leaving the appointment, clarify the next review date, who will communicate results, and whom to contact if the situation changes. Discuss difficulties with sleep, work, school, mobility, eating or emotional wellbeing when these are relevant. Practical support may require coordination between the treating clinician and other services.

The collected references do not establish a complete prevention or long-term outlook section for this entry. Missing information should not be interpreted as proof that prevention is impossible or that a particular outcome is inevitable. Ask what is known for the exact subtype, stage and personal circumstances, and which uncertainties remain.

When to seek emergency help

Severe breathing difficulty, collapse, new stroke-like symptoms, a seizure that is prolonged or repeated without recovery, uncontrolled major bleeding, or an immediate risk of self-harm require emergency help. In India, call 112 or reach the nearest emergency department. This is a general, non-exhaustive warning list; it is not a condition-specific triage tool.