Dubin-Johnson syndrome is a rare, inherited liver disorder characterized by impaired bilirubin excretion, resulting in the accumulation of bilirubin in liver cells. It was first described by Harold Dubin and Victor W. Johnson in 1954, hence the name.
Usually, the liver processes bilirubin and excretes it into the bile, which is then released into the intestine and ultimately eliminated from the body. However, in individuals with Dubin-Johnson syndrome, there is a defect in the liver cells’ ability to transport bilirubin from the liver into the bile. This leads to elevated levels of conjugated bilirubin (bilirubin that the liver has processed) in the bloodstream.
Epidemiology
Dubin-Johnson syndrome is an extremely rare disorder, and accurate prevalence data is limited. It is estimated to occur in approximately 1 in 20,000 to 1 in 100,000 individuals worldwide. The syndrome has been reported in various ethnic groups, but its prevalence may vary among populations. Mortality associated with Dubin-Johnson syndrome is extremely rare.
The condition itself does not typically cause severe liver dysfunction or life-threatening complications. Individuals with Dubin-Johnson syndrome usually have normal liver function tests and do not experience significant health problems related to the syndrome. Therefore, mortality directly attributed to Dubin-Johnson syndrome is uncommon.
However, it is important to note that complications unrelated to Dubin-Johnson syndrome or underlying liver conditions can occur in rare cases. For example, individuals with Dubin-Johnson syndrome may still be susceptible to other liver diseases or conditions that could impact their overall health. If a person with Dubin-Johnson syndrome develops a separate liver disorder or experiences other health complications, the associated mortality risk would depend on the specific condition and its severity.
Anatomy
Pathophysiology
The pathophysiology of Dubin-Johnson syndrome primarily involves a defect in bilirubin transport. Bilirubin is normally processed by the liver and excreted into the bile, which is then released into the intestine for elimination from the body. However, in individuals with Dubin-Johnson syndrome, there is an impairment in the transport of bilirubin from liver cells into the bile canaliculi.
Dubin-Johnson syndrome is primarily caused by mutations in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene. The ABCC2 gene provides instructions for producing the MRP2 protein, which is responsible for transporting bilirubin across the canalicular membrane of liver cells into the bile. When the ABCC2 gene is mutated, MRP2 function is compromised, leading to a reduced ability of liver cells to excrete bilirubin.
As a result of this defect, conjugated bilirubin, which is the form of bilirubin that has been processed by the liver, accumulates within the liver cells. The impaired transport of bilirubin out of the liver results in elevated levels of conjugated bilirubin in the bloodstream, a condition known as conjugated hyperbilirubinemia.
The accumulation of conjugated bilirubin in liver cells contributes to the characteristic features of Dubin-Johnson syndrome. One notable feature is the dark pigmentation of the liver, which is caused by the buildup of an epinephrine metabolite called melanin-like pigment. This pigment imparts a dark brown or black appearance to the liver tissue.
While the exact mechanisms underlying the accumulation of the pigment and its impact on liver function are not fully understood, it is believed that the altered bilirubin transport in Dubin-Johnson syndrome may affect the functioning of other transporters and cellular processes involved in the metabolism and excretion of various substances in the liver.
Etiology
The etiology, or underlying cause, of Dubin-Johnson syndrome, is primarily genetic. It is an inherited disorder typically transmitted in an autosomal recessive manner. This means an individual must inherit two copies of the mutated gene, one from each parent, to develop the syndrome. Dubin-Johnson syndrome is primarily associated with mutations in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene.
The ABCC2 gene provides instructions for producing the MRP2 protein, which is responsible for transporting bilirubin across the canalicular membrane of liver cells. Mutations in the ABCC2 gene lead to impaired function or reduced expression of the MRP2 protein, resulting in the defective bilirubin transport out of liver cells and into the bile.
The exact mechanisms by which these genetic mutations cause the impaired bilirubin transport seen in Dubin-Johnson syndrome are not fully understood. It is believed that the mutations affect the structure or function of the MRP2 protein, disrupting its ability to transport bilirubin. This leads to the accumulation of conjugated bilirubin within liver cells and elevated levels of conjugated bilirubin in the bloodstream.
While most cases of Dubin-Johnson syndrome are inherited, sporadic cases can also occur where there is no family history of the disorder. Sporadic cases may be due to de novo mutations, which are genetic changes that arise spontaneously in an individual with no previous family history of the condition.
Genetics
Prognostic Factors
The prognosis for individuals with Dubin-Johnson syndrome is generally excellent. This condition is considered benign, and most affected individuals have an average lifespan with no significant health complications related to the syndrome.
Dubin-Johnson syndrome does not typically cause severe liver dysfunction or progressive liver damage. Liver function tests, including measures of liver enzymes and bilirubin levels, are usually within normal ranges in individuals with the syndrome. The impairment in bilirubin excretion is not associated with liver failure or other serious liver-related conditions.
While the dark pigmentation of the liver is a characteristic feature of Dubin-Johnson syndrome, it does not directly impact liver function or lead to liver damage. The pigment accumulation in liver cells, known as a melanin-like pigment, does not cause significant harm to the liver or affect its overall function.
Clinical History
Clinical History
One of the characteristic features of Dubin-Johnson syndrome is the presence of darkly pigmented liver tissue. The liver may appear dark brown or black. This discoloration is caused by the accumulation of a pigment called melanin-like pigment or epinephrine metabolite in the liver cells.
Individuals with Dubin-Johnson syndrome have elevated levels of conjugated bilirubin in their bloodstream. Conjugated bilirubin is the form of bilirubin that the liver has processed. The impaired bilirubin transport into the bile leads to its accumulation in liver cells and subsequent elevation in the blood.
It is essential to recognize that Dubin-Johnson syndrome is a stable condition, and the clinical history does not typically involve progressive liver damage or worsening symptoms over time. The syndrome is usually benign, and individuals can have an average lifespan without significant health complications.
Physical Examination
Physical Examination
Some individuals with Dubin-Johnson syndrome may have mild jaundice, which is the yellowing of the skin and eyes. Jaundice occurs due to the elevated levels of bilirubin in the bloodstream. However, the jaundice is typically mild and not as pronounced as in other liver disorders. The most notable physical finding in Dubin-Johnson syndrome is the presence of darkly pigmented liver tissue. The liver may appear dark brown or black.
This discoloration is due to the accumulation of melanin-like pigment or epinephrine metabolite in the liver cells. Apart from the dark pigmentation of the liver and possible mild jaundice, individuals with Dubin-Johnson syndrome usually have an unremarkable physical examination. They generally do not exhibit signs of advanced liver disease, such as hepatomegaly, splenomegaly, or signs of liver failure.
Age group
Associated comorbidity
Associated activity
Acuity of presentation
Differential Diagnoses
Differential Diagnoses
Rotor Syndrome
Gilbert- -Meulengracht syndrome
Intrahepatic cholestasis
Laboratory Studies
Imaging Studies
Procedures
Histologic Findings
Staging
Treatment Paradigm
Dubin-Johnson syndrome (DJS) is a benign condition that does not progress to fibrosis or cirrhosis and typically does not necessitate any treatment. The significance of diagnosing DJS lies in ruling out other hepatobiliary disorders that may cause liver damage and identifying potentially treatable conditions. In cases of neonatal DJS with significant cholestasis, phenobarbital and ursodeoxycholic acid can be used as therapeutic options.
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Dubin-Johnson syndrome is a rare, inherited liver disorder characterized by impaired bilirubin excretion, resulting in the accumulation of bilirubin in liver cells. It was first described by Harold Dubin and Victor W. Johnson in 1954, hence the name.
Usually, the liver processes bilirubin and excretes it into the bile, which is then released into the intestine and ultimately eliminated from the body. However, in individuals with Dubin-Johnson syndrome, there is a defect in the liver cells’ ability to transport bilirubin from the liver into the bile. This leads to elevated levels of conjugated bilirubin (bilirubin that the liver has processed) in the bloodstream.
Dubin-Johnson syndrome is an extremely rare disorder, and accurate prevalence data is limited. It is estimated to occur in approximately 1 in 20,000 to 1 in 100,000 individuals worldwide. The syndrome has been reported in various ethnic groups, but its prevalence may vary among populations. Mortality associated with Dubin-Johnson syndrome is extremely rare.
The condition itself does not typically cause severe liver dysfunction or life-threatening complications. Individuals with Dubin-Johnson syndrome usually have normal liver function tests and do not experience significant health problems related to the syndrome. Therefore, mortality directly attributed to Dubin-Johnson syndrome is uncommon.
However, it is important to note that complications unrelated to Dubin-Johnson syndrome or underlying liver conditions can occur in rare cases. For example, individuals with Dubin-Johnson syndrome may still be susceptible to other liver diseases or conditions that could impact their overall health. If a person with Dubin-Johnson syndrome develops a separate liver disorder or experiences other health complications, the associated mortality risk would depend on the specific condition and its severity.
The pathophysiology of Dubin-Johnson syndrome primarily involves a defect in bilirubin transport. Bilirubin is normally processed by the liver and excreted into the bile, which is then released into the intestine for elimination from the body. However, in individuals with Dubin-Johnson syndrome, there is an impairment in the transport of bilirubin from liver cells into the bile canaliculi.
Dubin-Johnson syndrome is primarily caused by mutations in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene. The ABCC2 gene provides instructions for producing the MRP2 protein, which is responsible for transporting bilirubin across the canalicular membrane of liver cells into the bile. When the ABCC2 gene is mutated, MRP2 function is compromised, leading to a reduced ability of liver cells to excrete bilirubin.
As a result of this defect, conjugated bilirubin, which is the form of bilirubin that has been processed by the liver, accumulates within the liver cells. The impaired transport of bilirubin out of the liver results in elevated levels of conjugated bilirubin in the bloodstream, a condition known as conjugated hyperbilirubinemia.
The accumulation of conjugated bilirubin in liver cells contributes to the characteristic features of Dubin-Johnson syndrome. One notable feature is the dark pigmentation of the liver, which is caused by the buildup of an epinephrine metabolite called melanin-like pigment. This pigment imparts a dark brown or black appearance to the liver tissue.
While the exact mechanisms underlying the accumulation of the pigment and its impact on liver function are not fully understood, it is believed that the altered bilirubin transport in Dubin-Johnson syndrome may affect the functioning of other transporters and cellular processes involved in the metabolism and excretion of various substances in the liver.
The etiology, or underlying cause, of Dubin-Johnson syndrome, is primarily genetic. It is an inherited disorder typically transmitted in an autosomal recessive manner. This means an individual must inherit two copies of the mutated gene, one from each parent, to develop the syndrome. Dubin-Johnson syndrome is primarily associated with mutations in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene.
The ABCC2 gene provides instructions for producing the MRP2 protein, which is responsible for transporting bilirubin across the canalicular membrane of liver cells. Mutations in the ABCC2 gene lead to impaired function or reduced expression of the MRP2 protein, resulting in the defective bilirubin transport out of liver cells and into the bile.
The exact mechanisms by which these genetic mutations cause the impaired bilirubin transport seen in Dubin-Johnson syndrome are not fully understood. It is believed that the mutations affect the structure or function of the MRP2 protein, disrupting its ability to transport bilirubin. This leads to the accumulation of conjugated bilirubin within liver cells and elevated levels of conjugated bilirubin in the bloodstream.
While most cases of Dubin-Johnson syndrome are inherited, sporadic cases can also occur where there is no family history of the disorder. Sporadic cases may be due to de novo mutations, which are genetic changes that arise spontaneously in an individual with no previous family history of the condition.
The prognosis for individuals with Dubin-Johnson syndrome is generally excellent. This condition is considered benign, and most affected individuals have an average lifespan with no significant health complications related to the syndrome.
Dubin-Johnson syndrome does not typically cause severe liver dysfunction or progressive liver damage. Liver function tests, including measures of liver enzymes and bilirubin levels, are usually within normal ranges in individuals with the syndrome. The impairment in bilirubin excretion is not associated with liver failure or other serious liver-related conditions.
While the dark pigmentation of the liver is a characteristic feature of Dubin-Johnson syndrome, it does not directly impact liver function or lead to liver damage. The pigment accumulation in liver cells, known as a melanin-like pigment, does not cause significant harm to the liver or affect its overall function.
Clinical History
One of the characteristic features of Dubin-Johnson syndrome is the presence of darkly pigmented liver tissue. The liver may appear dark brown or black. This discoloration is caused by the accumulation of a pigment called melanin-like pigment or epinephrine metabolite in the liver cells.
Individuals with Dubin-Johnson syndrome have elevated levels of conjugated bilirubin in their bloodstream. Conjugated bilirubin is the form of bilirubin that the liver has processed. The impaired bilirubin transport into the bile leads to its accumulation in liver cells and subsequent elevation in the blood.
It is essential to recognize that Dubin-Johnson syndrome is a stable condition, and the clinical history does not typically involve progressive liver damage or worsening symptoms over time. The syndrome is usually benign, and individuals can have an average lifespan without significant health complications.
Physical Examination
Some individuals with Dubin-Johnson syndrome may have mild jaundice, which is the yellowing of the skin and eyes. Jaundice occurs due to the elevated levels of bilirubin in the bloodstream. However, the jaundice is typically mild and not as pronounced as in other liver disorders. The most notable physical finding in Dubin-Johnson syndrome is the presence of darkly pigmented liver tissue. The liver may appear dark brown or black.
This discoloration is due to the accumulation of melanin-like pigment or epinephrine metabolite in the liver cells. Apart from the dark pigmentation of the liver and possible mild jaundice, individuals with Dubin-Johnson syndrome usually have an unremarkable physical examination. They generally do not exhibit signs of advanced liver disease, such as hepatomegaly, splenomegaly, or signs of liver failure.
Differential Diagnoses
Rotor Syndrome
Gilbert- -Meulengracht syndrome
Intrahepatic cholestasis
Dubin-Johnson syndrome (DJS) is a benign condition that does not progress to fibrosis or cirrhosis and typically does not necessitate any treatment. The significance of diagnosing DJS lies in ruling out other hepatobiliary disorders that may cause liver damage and identifying potentially treatable conditions. In cases of neonatal DJS with significant cholestasis, phenobarbital and ursodeoxycholic acid can be used as therapeutic options.
medtigo
Dubin-Johnson Syndrome
Updated :
September 6, 2023
Dubin-Johnson syndrome is a rare, inherited liver disorder characterized by impaired bilirubin excretion, resulting in the accumulation of bilirubin in liver cells. It was first described by Harold Dubin and Victor W. Johnson in 1954, hence the name.
Usually, the liver processes bilirubin and excretes it into the bile, which is then released into the intestine and ultimately eliminated from the body. However, in individuals with Dubin-Johnson syndrome, there is a defect in the liver cells’ ability to transport bilirubin from the liver into the bile. This leads to elevated levels of conjugated bilirubin (bilirubin that the liver has processed) in the bloodstream.
Dubin-Johnson syndrome is an extremely rare disorder, and accurate prevalence data is limited. It is estimated to occur in approximately 1 in 20,000 to 1 in 100,000 individuals worldwide. The syndrome has been reported in various ethnic groups, but its prevalence may vary among populations. Mortality associated with Dubin-Johnson syndrome is extremely rare.
The condition itself does not typically cause severe liver dysfunction or life-threatening complications. Individuals with Dubin-Johnson syndrome usually have normal liver function tests and do not experience significant health problems related to the syndrome. Therefore, mortality directly attributed to Dubin-Johnson syndrome is uncommon.
However, it is important to note that complications unrelated to Dubin-Johnson syndrome or underlying liver conditions can occur in rare cases. For example, individuals with Dubin-Johnson syndrome may still be susceptible to other liver diseases or conditions that could impact their overall health. If a person with Dubin-Johnson syndrome develops a separate liver disorder or experiences other health complications, the associated mortality risk would depend on the specific condition and its severity.
The pathophysiology of Dubin-Johnson syndrome primarily involves a defect in bilirubin transport. Bilirubin is normally processed by the liver and excreted into the bile, which is then released into the intestine for elimination from the body. However, in individuals with Dubin-Johnson syndrome, there is an impairment in the transport of bilirubin from liver cells into the bile canaliculi.
Dubin-Johnson syndrome is primarily caused by mutations in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene. The ABCC2 gene provides instructions for producing the MRP2 protein, which is responsible for transporting bilirubin across the canalicular membrane of liver cells into the bile. When the ABCC2 gene is mutated, MRP2 function is compromised, leading to a reduced ability of liver cells to excrete bilirubin.
As a result of this defect, conjugated bilirubin, which is the form of bilirubin that has been processed by the liver, accumulates within the liver cells. The impaired transport of bilirubin out of the liver results in elevated levels of conjugated bilirubin in the bloodstream, a condition known as conjugated hyperbilirubinemia.
The accumulation of conjugated bilirubin in liver cells contributes to the characteristic features of Dubin-Johnson syndrome. One notable feature is the dark pigmentation of the liver, which is caused by the buildup of an epinephrine metabolite called melanin-like pigment. This pigment imparts a dark brown or black appearance to the liver tissue.
While the exact mechanisms underlying the accumulation of the pigment and its impact on liver function are not fully understood, it is believed that the altered bilirubin transport in Dubin-Johnson syndrome may affect the functioning of other transporters and cellular processes involved in the metabolism and excretion of various substances in the liver.
The etiology, or underlying cause, of Dubin-Johnson syndrome, is primarily genetic. It is an inherited disorder typically transmitted in an autosomal recessive manner. This means an individual must inherit two copies of the mutated gene, one from each parent, to develop the syndrome. Dubin-Johnson syndrome is primarily associated with mutations in the ABCC2 gene, also known as the multidrug resistance-associated protein 2 (MRP2) gene.
The ABCC2 gene provides instructions for producing the MRP2 protein, which is responsible for transporting bilirubin across the canalicular membrane of liver cells. Mutations in the ABCC2 gene lead to impaired function or reduced expression of the MRP2 protein, resulting in the defective bilirubin transport out of liver cells and into the bile.
The exact mechanisms by which these genetic mutations cause the impaired bilirubin transport seen in Dubin-Johnson syndrome are not fully understood. It is believed that the mutations affect the structure or function of the MRP2 protein, disrupting its ability to transport bilirubin. This leads to the accumulation of conjugated bilirubin within liver cells and elevated levels of conjugated bilirubin in the bloodstream.
While most cases of Dubin-Johnson syndrome are inherited, sporadic cases can also occur where there is no family history of the disorder. Sporadic cases may be due to de novo mutations, which are genetic changes that arise spontaneously in an individual with no previous family history of the condition.
The prognosis for individuals with Dubin-Johnson syndrome is generally excellent. This condition is considered benign, and most affected individuals have an average lifespan with no significant health complications related to the syndrome.
Dubin-Johnson syndrome does not typically cause severe liver dysfunction or progressive liver damage. Liver function tests, including measures of liver enzymes and bilirubin levels, are usually within normal ranges in individuals with the syndrome. The impairment in bilirubin excretion is not associated with liver failure or other serious liver-related conditions.
While the dark pigmentation of the liver is a characteristic feature of Dubin-Johnson syndrome, it does not directly impact liver function or lead to liver damage. The pigment accumulation in liver cells, known as a melanin-like pigment, does not cause significant harm to the liver or affect its overall function.
Clinical History
One of the characteristic features of Dubin-Johnson syndrome is the presence of darkly pigmented liver tissue. The liver may appear dark brown or black. This discoloration is caused by the accumulation of a pigment called melanin-like pigment or epinephrine metabolite in the liver cells.
Individuals with Dubin-Johnson syndrome have elevated levels of conjugated bilirubin in their bloodstream. Conjugated bilirubin is the form of bilirubin that the liver has processed. The impaired bilirubin transport into the bile leads to its accumulation in liver cells and subsequent elevation in the blood.
It is essential to recognize that Dubin-Johnson syndrome is a stable condition, and the clinical history does not typically involve progressive liver damage or worsening symptoms over time. The syndrome is usually benign, and individuals can have an average lifespan without significant health complications.
Physical Examination
Some individuals with Dubin-Johnson syndrome may have mild jaundice, which is the yellowing of the skin and eyes. Jaundice occurs due to the elevated levels of bilirubin in the bloodstream. However, the jaundice is typically mild and not as pronounced as in other liver disorders. The most notable physical finding in Dubin-Johnson syndrome is the presence of darkly pigmented liver tissue. The liver may appear dark brown or black.
This discoloration is due to the accumulation of melanin-like pigment or epinephrine metabolite in the liver cells. Apart from the dark pigmentation of the liver and possible mild jaundice, individuals with Dubin-Johnson syndrome usually have an unremarkable physical examination. They generally do not exhibit signs of advanced liver disease, such as hepatomegaly, splenomegaly, or signs of liver failure.
Differential Diagnoses
Rotor Syndrome
Gilbert- -Meulengracht syndrome
Intrahepatic cholestasis
Dubin-Johnson syndrome (DJS) is a benign condition that does not progress to fibrosis or cirrhosis and typically does not necessitate any treatment. The significance of diagnosing DJS lies in ruling out other hepatobiliary disorders that may cause liver damage and identifying potentially treatable conditions. In cases of neonatal DJS with significant cholestasis, phenobarbital and ursodeoxycholic acid can be used as therapeutic options.
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