Gilbert’s Syndrome, Signs/Symptoms and Diagnosis
- The patient serum is needed.
- A random sample can be taken.
- Avoid sample from the light.
Definition of Gilbert’s Syndrome
- 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 is also called Constitutional Hepatic dysfunction or familial nonhemolytic jaundice.
- Gilbert’s syndrome is benign, intermittent, familial, autosomal dominant, with non-hemolytic jaundice (unconjugated hyperbilirubinemia), usually discovered on routine laboratory tests.
- This may affect 3% to 5% of the population.
Pathophysiology of Gilbert’s Syndrome
- To understand Gilbert’s syndrome, the following diagram of bilirubin metabolism gives about the situation in Gilbert’s syndrome.
Mechanism of Gilbert’s syndrome:
- Gilbert’s syndrome is a common, mild liver condition in which the liver doesn’t properly process bilirubin.
- Gilbert’s syndrome is a nonhemolytic condition and is an autosomal dominant character.
- Liver glucuronyltransferase activity is low due to a mutation in the bilirubin-UDP-glucuronosyl-transferase gene.
- It is a heterozygous group with raised bilirubin.
- It is inherited in an autosomal recessive pattern.
- There is an increase in unconjugated bilirubin usually <3 mg/dL.
- Bilirubin fluctuates between 1.5 to 3 mg/dL.
- Bilirubin will increase with fasting.
- It is a benign condition and occurs in 2% of the population.
- The breakdown of red blood cells produces bilirubin.
- The hyperbilirubinemia is due to the reduced activity of the Glucuronyltransferase enzyme.
- There is no role in hemolysis, and hyperbilirubinemia is due to the deficiency of the enzyme.
- Glucuronyl transferase enzymes typically have 10% to 35% reduced activity.
- Glucuronyl Transferase enzyme is needed for the conjugation of the bilirubin.
- There is an increase in the bilirubin monoglucuronide (unconjugated bilirubin).
- Conjugation renders the bilirubin water-soluble excreted into the bile and duodenum.
- These patients are given phenobarbital, which normalizes bilirubin and hepatic bilirubin clearance.
Signs and symptoms of Gilbert’s syndrome:
- Male is affected 1.5 to 7.3 times more than females.
- It is also seen in the siblings of Gilbert’s syndrome patients.
- Most patients are asymptomatic.
- The onset is shortly after birth but may be unnoticed for many years.
- There may be yellowness of the eyes and the skin in some cases.
- The most common finding is the presence of jaundice due to raised total bilirubin. This bilirubin is usually <3 mg/dL.
- The bilirubin level fluctuates, and even some time may be normal. When these patients are followed, then 25% may show normal values.
- There may be fatigue.
- Jaundice may be seen due to:
- Intercurrent illness.
- Reduced caloric intake.
- Alcohol use.
- Rigorous exercise.
- Lake of sleep.
- various drugs.
- Alcohol intake.
- Birth control pills.
- These cases are usually diagnosed near puberty or adult life during a routine examination.
Diagnosis of Gilbert’s syndrome:
- There is no satisfactory specific test for the diagnosis of Gilbert’s syndrome.
- It may be followed for 12 to 18 months with follow-up of liver function tests.
- Gilbert’s syndrome is confirmed if there are no constitutional symptoms, no abnormal liver function tests except raised total bilirubin, and mainly unconjugated.
- Exclusion of other diseases.
- Caloric deprivation test: If the patient diet is restricted to 400 calories/day will lead to raising the level of total bilirubin >0.8 mg/dl, suggesting Gilbert’s syndrome. Non-Gilbert’s syndrome patients will have less than this (<0.5 mg/dL).
- Bilirubin level comes to normal after 12 to 14 hours after taking a normal diet.
- Indirect serum bilirubin is increased (Indirect bilirubin seen in around 85% of the cases). It is usually less than 4 mg/100 ml.
- Rarely It may increase to 18 mg/100 ml, then needs treatment.
- Fecal urobilinogen is decreased but maybe even normal.
- Urine shows no bilirubin.
- The liver function test is usually normal.
- Albumin is normal.
- Prothrombin time is normal.
- Liver biopsy is normal. It does not show any significant changes.
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.
- These patients do not need treatment until bilirubin is high. Because mostly, the bilirubin is very low.
- Give reassurance to the patient that he does not suffer from liver disease.
Avoid acetaminophen because it is metabolized by glucuronidation. This gives rise to a toxic reaction.
List of Defective hepatic unconjugated bilirubin clearance due to defective uptake or conjugation:
- Gilbert’s syndrome.
- Crigler-Najjar type 1 and type II.
- Liver diseases (severe).
- Congestive heart failure.
- Drug-induced inhibition.
- Sometimes hyperthyroidism.
- Portacaval shunt.