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Gilbert Syndrome

Updated : January 25, 2024





Background

Gilbert syndrome is a common, inherited condition that affects how the liver processes bilirubin, a waste product formed from the breakdown of red blood cells. Bilirubin is normally processed by the liver and excreted into the bile, which is then eliminated from the body through the digestive system. In Gilbert syndrome, there is a deficiency in the enzyme responsible for processing bilirubin, called UDP-glucuronosyltransferase 1A1 (UGT1A1).

This results in a buildup of bilirubin in the blood, which can cause jaundice (yellowing of the skin and eyes) and other symptoms. Gilbert syndrome is usually asymptomatic, meaning that most people with the condition do not experience any symptoms or only have mild symptoms that do not affect their daily life. However, some people with Gilbert syndrome may experience episodes of jaundice, fatigue, abdominal pain, and other symptoms.

Gilbert syndrome is a genetic condition, and it is inherited in an autosomal recessive manner. This means that a person must inherit two copies of the defective gene (one from each parent) to develop the condition. The gene responsible for Gilbert syndrome is located on chromosome 2, and it is known as UGT1A1.

Epidemiology

Gilbert syndrome is a relatively common condition, with a prevalence estimated to be between 3% and 10% in the general population. However, the exact prevalence may vary depending on the population studied and the diagnostic criteria used. The condition is more common in men than in women, and it tends to be diagnosed during adolescence or early adulthood. It is also more common in people of European descent than in other ethnic groups.

Gilbert syndrome is typically diagnosed based on clinical symptoms and laboratory tests that measure bilirubin levels in the blood. However, because the condition is often asymptomatic or has mild symptoms, it is likely that many cases go undiagnosed. Overall, Gilbert syndrome is a benign condition that does not usually require treatment. However, people with the condition may need to avoid certain medications and be monitored for complications such as gallstones or liver damage.

Anatomy

Pathophysiology

Gilbert syndrome is caused by a deficiency in the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is responsible for the conjugation of bilirubin in the liver. Bilirubin is a waste product formed from the breakdown of hemoglobin in red blood cells, and it is normally excreted in the bile and eliminated from the body through the digestive system.

In people with Gilbert syndrome, the UGT1A1 enzyme is deficient or less active than usual, leading to a buildup of unconjugated bilirubin in the blood. Unconjugated bilirubin is not water-soluble and cannot be eliminated from the body easily, so it can accumulate in the body’s tissues, causing jaundice and other symptoms.

The severity of Gilbert syndrome varies widely among individuals, and some people may have no symptoms at all. The degree of enzyme deficiency is also variable, with some people having a complete absence of UGT1A1 activity while others have only a partial deficiency. The condition is usually diagnosed based on elevated levels of unconjugated bilirubin in the blood, which can be caused by a number of factors, including fasting, dehydration, and stress.

The diagnosis can be confirmed by genetic testing to identify mutations in the UGT1A1 gene. Treatment for Gilbert syndrome is usually not necessary, as the condition is benign and does not typically cause significant health problems. However, people with the condition may need to avoid certain medications that can exacerbate symptoms, such as phenobarbital and other drugs that increase the breakdown of red blood cells.

Etiology

The primary cause of Gilbert syndrome is a genetic mutation that affects the function of the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, which is responsible for the conjugation of bilirubin in the liver. The UGT1A1 enzyme adds a molecule called glucuronic acid to bilirubin, which makes it more water-soluble and easier to eliminate from the body. In people with Gilbert syndrome, there is a mutation in the UGT1A1 gene that reduces the activity of the enzyme.

This leads to a buildup of unconjugated bilirubin in the blood, which can cause jaundice and other symptoms. Gilbert syndrome is an autosomal recessive condition, which means that a person must inherit two copies of the defective UGT1A1 gene (one from each parent) to develop the condition. If a person inherits only one copy of the gene, they are considered a carrier of the condition, but they do not usually experience symptoms. The specific genetic mutations that cause Gilbert syndrome are known as UGT1A128 and UGT1A137.

These mutations are relatively common, with UGT1A1*28 being present in up to 40% of the population in some ethnic groups. Other factors can also affect bilirubin levels in the blood, such as fasting, dehydration, and stress, which can trigger symptoms in people with Gilbert syndrome. Additionally, some medications can increase bilirubin levels and exacerbate symptoms, so people with the condition should avoid drugs that increase the breakdown of red blood cells.

Genetics

Prognostic Factors

The prognosis for Gilbert syndrome is generally good. The condition is usually benign and does not cause any long-term health problems or affect life expectancy. Most people with Gilbert syndrome have a normal lifespan and do not require any specific treatment. Episodes of jaundice can occur, especially during times of stress, illness, or fasting, but they are usually mild and self-limiting.

Symptoms may improve with rest, hydration, and avoiding triggers such as fasting or stress. While Gilbert syndrome is a lifelong condition, it does not usually require any significant lifestyle changes or medical treatment. However, people with Gilbert syndrome should be aware of their condition and take steps to manage it appropriately.

This may include regular check-ups with a healthcare provider to monitor bilirubin levels and liver function, avoiding triggers such as fasting and stress, and reviewing medications with a healthcare provider to ensure they are safe to use. In summary, while Gilbert syndrome can cause episodes of jaundice, it is usually a benign condition that does not significantly impact life expectancy or quality of life. With appropriate management and monitoring, people with Gilbert syndrome can lead normal, healthy lives.

Clinical History

Clinical history

Gilbert syndrome is a genetic disorder that affects the way the liver processes bilirubin, a yellow pigment produced by the breakdown of red blood cells. People with Gilbert syndrome have higher than normal levels of unconjugated bilirubin in their blood, which can cause yellowing of the skin and whites of the eyes (jaundice) and fatigue. The condition is usually benign and does not cause any long-term health problems.

The clinical history of Gilbert syndrome typically includes the following features:

Age of onset: Gilbert syndrome usually presents in adolescence or early adulthood, although it can occur at any age.

Jaundice: The most common symptom of Gilbert syndrome is the yellowing of the skin and whites of the eyes, which can range from mild to severe. Jaundice may be triggered by fasting, stress, or illness.

Fatigue: Some people with Gilbert syndrome may experience fatigue or weakness, especially during episodes of jaundice.

No other symptoms: Gilbert syndrome does not cause any other symptoms, such as abdominal pain or nausea.

Family history: Gilbert syndrome is an inherited condition, so people with the disorder often have a family history of jaundice or liver problems.

Blood tests: Diagnosis of Gilbert syndrome is usually based on blood tests that show elevated levels of unconjugated bilirubin and normal liver function tests.

While Gilbert syndrome is a lifelong condition, it is usually manageable with lifestyle modifications and periodic monitoring. People with Gilbert syndrome should avoid fasting, eat a healthy diet, and avoid triggers that can cause jaundice. Regular check-ups with a healthcare provider can help ensure that the condition is well-controlled.

Physical Examination

Physical examination

Physical examination of Gilbert syndrome typically reveals the following findings:

Jaundice: The most prominent feature of Gilbert syndrome is the yellowing of the skin and whites of the eyes (jaundice). Jaundice can vary in severity and may be more prominent during periods of fasting, stress, or illness.

Normal vital signs: People with Gilbert syndrome usually have normal vital signs, including blood pressure, heart rate, and respiratory rate.

Normal abdominal exam: The liver and spleen are usually normal in size and non-tender to palpation. There is no evidence of ascites or other signs of liver disease.

No other abnormalities: Gilbert syndrome does not cause any other physical abnormalities or signs of illness.

Age group

Associated comorbidity

Associated activity

Acuity of presentation

Differential Diagnoses

Differential diagnosis

The diagnosis of Gilbert syndrome can be challenging because the symptoms are non-specific and can be caused by a variety of other conditions. Therefore, it is important to consider other potential causes of jaundice and elevated bilirubin levels in the blood when evaluating a patient suspected of having Gilbert syndrome. Some conditions that can mimic the symptoms of Gilbert syndrome include:

Crigler-Najjar syndrome: This is a rare inherited disorder that also affects the UGT1A1 enzyme and causes severe unconjugated hyperbilirubinemia. Unlike Gilbert syndrome, Crigler-Najjar syndrome is usually diagnosed in infancy and can be life-threatening without treatment.

Dubin-Johnson syndrome: This is a rare inherited disorder that causes chronic conjugated hyperbilirubinemia due to impaired excretion of bilirubin from the liver. Unlike Gilbert syndrome, Dubin-Johnson syndrome usually presents with dark urine and other symptoms of chronic liver disease.

Hemolysis: Increased breakdown of red blood cells can cause an increase in unconjugated bilirubin levels, leading to jaundice. Hemolysis can be caused by a variety of factors, including infections, autoimmune disorders, and medications.

Viral hepatitis: Hepatitis A, B, and C can all cause elevated bilirubin levels and jaundice. Other symptoms may include fever, fatigue, and abdominal pain.

Other liver diseases: Cirrhosis, fatty liver disease, and other liver disorders can also cause jaundice and elevated bilirubin levels. These conditions may be diagnosed based on liver function tests, imaging studies, and biopsies.

It is important to consult a healthcare provider for an accurate diagnosis and appropriate treatment. Blood tests and genetic testing may be performed to confirm a diagnosis of Gilbert syndrome and rule out other potential causes of jaundice and elevated bilirubin levels.

Laboratory Studies

Imaging Studies

Procedures

Histologic Findings

Staging

Treatment Paradigm

The management of Gilbert syndrome is focused on preventing and managing episodes of jaundice and maintaining good health.

Here are some key aspects of management:

Avoid fasting: Fasting or skipping meals can trigger jaundice in people with Gilbert syndrome. Therefore, it is important to eat regular, balanced meals and avoid prolonged fasting.

Manage stress: Stress can also trigger jaundice in some people with Gilbert syndrome. Stress management techniques such as exercise, meditation, or deep breathing can help reduce stress levels.

Medication review: Certain medications, such as rifampin, can increase bilirubin levels and should be avoided or used with caution in people with Gilbert syndrome. It is important to review all medications with a healthcare provider to ensure they are safe for people with Gilbert syndrome.

Treat underlying conditions: If there are any underlying conditions that may contribute to jaundice, such as viral hepatitis or liver disease, they should be appropriately managed.

Regular check-ups: Regular check-ups with a healthcare provider can help monitor bilirubin levels and liver function. Blood tests can be used to monitor bilirubin levels and ensure that liver function is normal.

by Stage

by Modality

Chemotherapy

Radiation Therapy

Surgical Interventions

Hormone Therapy

Immunotherapy

Hyperthermia

Photodynamic Therapy

Stem Cell Transplant

Targeted Therapy

Palliative Care

Medication

Media Gallary

References

https://www.ncbi.nlm.nih.gov/books/NBK470200/

Gilbert Syndrome

Updated : January 25, 2024




Gilbert syndrome is a common, inherited condition that affects how the liver processes bilirubin, a waste product formed from the breakdown of red blood cells. Bilirubin is normally processed by the liver and excreted into the bile, which is then eliminated from the body through the digestive system. In Gilbert syndrome, there is a deficiency in the enzyme responsible for processing bilirubin, called UDP-glucuronosyltransferase 1A1 (UGT1A1).

This results in a buildup of bilirubin in the blood, which can cause jaundice (yellowing of the skin and eyes) and other symptoms. Gilbert syndrome is usually asymptomatic, meaning that most people with the condition do not experience any symptoms or only have mild symptoms that do not affect their daily life. However, some people with Gilbert syndrome may experience episodes of jaundice, fatigue, abdominal pain, and other symptoms.

Gilbert syndrome is a genetic condition, and it is inherited in an autosomal recessive manner. This means that a person must inherit two copies of the defective gene (one from each parent) to develop the condition. The gene responsible for Gilbert syndrome is located on chromosome 2, and it is known as UGT1A1.

Gilbert syndrome is a relatively common condition, with a prevalence estimated to be between 3% and 10% in the general population. However, the exact prevalence may vary depending on the population studied and the diagnostic criteria used. The condition is more common in men than in women, and it tends to be diagnosed during adolescence or early adulthood. It is also more common in people of European descent than in other ethnic groups.

Gilbert syndrome is typically diagnosed based on clinical symptoms and laboratory tests that measure bilirubin levels in the blood. However, because the condition is often asymptomatic or has mild symptoms, it is likely that many cases go undiagnosed. Overall, Gilbert syndrome is a benign condition that does not usually require treatment. However, people with the condition may need to avoid certain medications and be monitored for complications such as gallstones or liver damage.

Gilbert syndrome is caused by a deficiency in the enzyme UDP-glucuronosyltransferase 1A1 (UGT1A1), which is responsible for the conjugation of bilirubin in the liver. Bilirubin is a waste product formed from the breakdown of hemoglobin in red blood cells, and it is normally excreted in the bile and eliminated from the body through the digestive system.

In people with Gilbert syndrome, the UGT1A1 enzyme is deficient or less active than usual, leading to a buildup of unconjugated bilirubin in the blood. Unconjugated bilirubin is not water-soluble and cannot be eliminated from the body easily, so it can accumulate in the body’s tissues, causing jaundice and other symptoms.

The severity of Gilbert syndrome varies widely among individuals, and some people may have no symptoms at all. The degree of enzyme deficiency is also variable, with some people having a complete absence of UGT1A1 activity while others have only a partial deficiency. The condition is usually diagnosed based on elevated levels of unconjugated bilirubin in the blood, which can be caused by a number of factors, including fasting, dehydration, and stress.

The diagnosis can be confirmed by genetic testing to identify mutations in the UGT1A1 gene. Treatment for Gilbert syndrome is usually not necessary, as the condition is benign and does not typically cause significant health problems. However, people with the condition may need to avoid certain medications that can exacerbate symptoms, such as phenobarbital and other drugs that increase the breakdown of red blood cells.

The primary cause of Gilbert syndrome is a genetic mutation that affects the function of the UDP-glucuronosyltransferase 1A1 (UGT1A1) enzyme, which is responsible for the conjugation of bilirubin in the liver. The UGT1A1 enzyme adds a molecule called glucuronic acid to bilirubin, which makes it more water-soluble and easier to eliminate from the body. In people with Gilbert syndrome, there is a mutation in the UGT1A1 gene that reduces the activity of the enzyme.

This leads to a buildup of unconjugated bilirubin in the blood, which can cause jaundice and other symptoms. Gilbert syndrome is an autosomal recessive condition, which means that a person must inherit two copies of the defective UGT1A1 gene (one from each parent) to develop the condition. If a person inherits only one copy of the gene, they are considered a carrier of the condition, but they do not usually experience symptoms. The specific genetic mutations that cause Gilbert syndrome are known as UGT1A128 and UGT1A137.

These mutations are relatively common, with UGT1A1*28 being present in up to 40% of the population in some ethnic groups. Other factors can also affect bilirubin levels in the blood, such as fasting, dehydration, and stress, which can trigger symptoms in people with Gilbert syndrome. Additionally, some medications can increase bilirubin levels and exacerbate symptoms, so people with the condition should avoid drugs that increase the breakdown of red blood cells.

The prognosis for Gilbert syndrome is generally good. The condition is usually benign and does not cause any long-term health problems or affect life expectancy. Most people with Gilbert syndrome have a normal lifespan and do not require any specific treatment. Episodes of jaundice can occur, especially during times of stress, illness, or fasting, but they are usually mild and self-limiting.

Symptoms may improve with rest, hydration, and avoiding triggers such as fasting or stress. While Gilbert syndrome is a lifelong condition, it does not usually require any significant lifestyle changes or medical treatment. However, people with Gilbert syndrome should be aware of their condition and take steps to manage it appropriately.

This may include regular check-ups with a healthcare provider to monitor bilirubin levels and liver function, avoiding triggers such as fasting and stress, and reviewing medications with a healthcare provider to ensure they are safe to use. In summary, while Gilbert syndrome can cause episodes of jaundice, it is usually a benign condition that does not significantly impact life expectancy or quality of life. With appropriate management and monitoring, people with Gilbert syndrome can lead normal, healthy lives.

Clinical history

Gilbert syndrome is a genetic disorder that affects the way the liver processes bilirubin, a yellow pigment produced by the breakdown of red blood cells. People with Gilbert syndrome have higher than normal levels of unconjugated bilirubin in their blood, which can cause yellowing of the skin and whites of the eyes (jaundice) and fatigue. The condition is usually benign and does not cause any long-term health problems.

The clinical history of Gilbert syndrome typically includes the following features:

Age of onset: Gilbert syndrome usually presents in adolescence or early adulthood, although it can occur at any age.

Jaundice: The most common symptom of Gilbert syndrome is the yellowing of the skin and whites of the eyes, which can range from mild to severe. Jaundice may be triggered by fasting, stress, or illness.

Fatigue: Some people with Gilbert syndrome may experience fatigue or weakness, especially during episodes of jaundice.

No other symptoms: Gilbert syndrome does not cause any other symptoms, such as abdominal pain or nausea.

Family history: Gilbert syndrome is an inherited condition, so people with the disorder often have a family history of jaundice or liver problems.

Blood tests: Diagnosis of Gilbert syndrome is usually based on blood tests that show elevated levels of unconjugated bilirubin and normal liver function tests.

While Gilbert syndrome is a lifelong condition, it is usually manageable with lifestyle modifications and periodic monitoring. People with Gilbert syndrome should avoid fasting, eat a healthy diet, and avoid triggers that can cause jaundice. Regular check-ups with a healthcare provider can help ensure that the condition is well-controlled.

Physical examination

Physical examination of Gilbert syndrome typically reveals the following findings:

Jaundice: The most prominent feature of Gilbert syndrome is the yellowing of the skin and whites of the eyes (jaundice). Jaundice can vary in severity and may be more prominent during periods of fasting, stress, or illness.

Normal vital signs: People with Gilbert syndrome usually have normal vital signs, including blood pressure, heart rate, and respiratory rate.

Normal abdominal exam: The liver and spleen are usually normal in size and non-tender to palpation. There is no evidence of ascites or other signs of liver disease.

No other abnormalities: Gilbert syndrome does not cause any other physical abnormalities or signs of illness.

Differential diagnosis

The diagnosis of Gilbert syndrome can be challenging because the symptoms are non-specific and can be caused by a variety of other conditions. Therefore, it is important to consider other potential causes of jaundice and elevated bilirubin levels in the blood when evaluating a patient suspected of having Gilbert syndrome. Some conditions that can mimic the symptoms of Gilbert syndrome include:

Crigler-Najjar syndrome: This is a rare inherited disorder that also affects the UGT1A1 enzyme and causes severe unconjugated hyperbilirubinemia. Unlike Gilbert syndrome, Crigler-Najjar syndrome is usually diagnosed in infancy and can be life-threatening without treatment.

Dubin-Johnson syndrome: This is a rare inherited disorder that causes chronic conjugated hyperbilirubinemia due to impaired excretion of bilirubin from the liver. Unlike Gilbert syndrome, Dubin-Johnson syndrome usually presents with dark urine and other symptoms of chronic liver disease.

Hemolysis: Increased breakdown of red blood cells can cause an increase in unconjugated bilirubin levels, leading to jaundice. Hemolysis can be caused by a variety of factors, including infections, autoimmune disorders, and medications.

Viral hepatitis: Hepatitis A, B, and C can all cause elevated bilirubin levels and jaundice. Other symptoms may include fever, fatigue, and abdominal pain.

Other liver diseases: Cirrhosis, fatty liver disease, and other liver disorders can also cause jaundice and elevated bilirubin levels. These conditions may be diagnosed based on liver function tests, imaging studies, and biopsies.

It is important to consult a healthcare provider for an accurate diagnosis and appropriate treatment. Blood tests and genetic testing may be performed to confirm a diagnosis of Gilbert syndrome and rule out other potential causes of jaundice and elevated bilirubin levels.

The management of Gilbert syndrome is focused on preventing and managing episodes of jaundice and maintaining good health.

Here are some key aspects of management:

Avoid fasting: Fasting or skipping meals can trigger jaundice in people with Gilbert syndrome. Therefore, it is important to eat regular, balanced meals and avoid prolonged fasting.

Manage stress: Stress can also trigger jaundice in some people with Gilbert syndrome. Stress management techniques such as exercise, meditation, or deep breathing can help reduce stress levels.

Medication review: Certain medications, such as rifampin, can increase bilirubin levels and should be avoided or used with caution in people with Gilbert syndrome. It is important to review all medications with a healthcare provider to ensure they are safe for people with Gilbert syndrome.

Treat underlying conditions: If there are any underlying conditions that may contribute to jaundice, such as viral hepatitis or liver disease, they should be appropriately managed.

Regular check-ups: Regular check-ups with a healthcare provider can help monitor bilirubin levels and liver function. Blood tests can be used to monitor bilirubin levels and ensure that liver function is normal.

https://www.ncbi.nlm.nih.gov/books/NBK470200/