Gilbert’s Syndrome part 1

February 12, 2020Chemical pathologyLab Tests

Sample

• The patient serum is needed.
• A random sample can be taken.

Precaution

• Avoid sample from the light.

Definition

• This syndrome is characterized by mild unconjugated hyperbilirubinemia.
  • Nearly all unconjugated bilirubin is detected.
  • This is a benign harmless condition because there is a mild increase in the unconjugated bilirubin.
• Gilbert’s disease also called Constitutional Hepatic dysfunction or familial nonhemolytic jaundice.
• This may affect 3 to 5% of the population.

Pathophysiology

1. To understand Gilbert’s syndrome, the following diagram gives the picture of bilirubin formation and metabolism.
   1. Hemolysis of the RBCs gives rise to unconjugated bilirubin.
   2. It is carried by the carrier protein to the liver.
   3. In the liver, conjugation takes place with the help of a glucoronyl tranferase enzyme.
   4. In Gilbert’s syndrome, there is a deficiency of glucoronyl transferase enzyme.

Mechanism of Gilbert’s syndrome

2. Gilbert’s syndrome is a common, mild liver condition in which the liver doesn’t properly process bilirubin.
3. Gilbert’s syndrome is a nonhemolytic condition and is an autosomal dominant character.
   1. Liver glucuronyltransferase activity is low due to a mutation in the bilirubin-UDP-glucuronosyl-transferase gene.
   2. This heterozygous group with raised bilirubin.
   3. This is inherited in an autosomal recessive pattern.
   4. There is an increase in unconjugated bilirubin usually <3 mg/dL.
      1. Bilirubin fluctuates between 1.5 to 3 mg/dL.
      2. Bilirubin will increase with fasting.
   5. This is a benign condition and occurs in 2% of the population.
4.  Bilirubin is produced by the breakdown of red blood cells.
5. The hyperbilirubinemia is due to the reduced activity of the Glucuronyltransferase enzyme.
   1. There is no role of hemolysis and hyperbilirubinemia is due to the deficiency of the enzyme.
   2. Glucuronyl transferase enzymes typically have 10 to 35% reduced activity.
   3. Glucuronyl Transferase enzyme is needed for the conjugation of the bilirubin.
6. There is an increase in the bilirubin monoglucuronide (unconjugated bilirubin).
7. Conjugation renders the bilirubin water-soluble, which is excreted into the bile and duodenum.
8. When these patients are given phenobarbital, that normalizes bilirubin and hepatic bilirubin clearance.

Sign and symptom:

1. Most patients are asymptomatic.
2. The onset is shortly after birth but may be unnoticed for many years.
3. There may be yellowness of the eyes and the skin in some cases.
4. The most common finding is the presence of jaundice due to raised bilirubin. This bilirubin is usually <3 mg/dL.
5. The bilirubin level fluctuates and even some time may be normal. When these patients are followed then 25% may shows normal values.
6. There may be fatigue.
7. The elevated values may be seen due to:
   1. Stress.
   2. Fatigue.
   3. Intercurrent illness.
   4. Reduced caloric intake.
   5. Alcohol use.
   6. Rigorous exercise.
   7. Lake of sleep.
8. These cases are usually diagnosed near puberty or adult life during a routine examination.

 Diagnosis:

1. Indirect serum bilirubin is increased (This indirect is around 85%). It is usually less than 4 mg/ 100 ml.
   1. Rarely It may increase to 18 mg /100 ml, then needs treatment.
2. Fecal urobilinogen is decreased.
3. Urine shows no bilirubin.
4. The liver function test is usually normal.
5. Albumin is normal.
6. Prothrombin time is normal.
7. Liver biopsy is normal.

Importance of diagnosis of Gilbert’s syndrome:

• Some people misdiagnose this condition as chronic hepatitis.
• This is differentiated by the absence of anemia and bilirubin in the urine.
• Liver function tests are normal.

Treatment:

• These patients do not need treatment until bilirubin is high. Because mostly the bilirubin is very low.
• Give reassurance to the patients that he does not suffer liver disease.
• Avoid acetaminophen because it is metabolized by glucuronidation. This gives rise to a toxic reaction.

Possible References Used