Causes of Gilbert’s Syndrome

What is Bilirubin?

Bilirubin is a normal by-product that is formed after the breakdown of old red blood cells. It contains haemoglobin - an oxygen carrying protein in blood.

Normally the life span of a red blood cell is around 120 days. When they expire the haemoglobin is broken down into heme and globin. Globin is a protein that is stored by the body for later use. Heme needs to be excreted from the body.

The removal of heme is called glucuronidation. Here the heme breaks down into orangey-yellow pigment known as ‘free’ or unconjugated bilirubin. This free bilirubin goes to the liver. It is soluble in fat.

In the liver the bilirubin is metabolised by an enzyme called urodine diphosphate glucuronosyltransferase (UGT) and changes into a water-soluble form. This is known as ‘conjugated’ bilirubin.

The conjugated bilirubin is secreted into bile and bile helps in digestion. Bile is stored in the gall bladder from where it is released into the small intestine. In the intestine it is converted by bacteria into pigment substances like urobilinogen. It is excreted thereafter in feces and urine.

What causes Gilbert’s syndrome?

In patients of Gilbert’s syndrome there is a lack or deficiency of UGT enzyme. This prevents modification of bilirubin at a normal rate. This leads to the rise in ‘unconjugated’ bilirubin.

Testing for Gilbert’s syndrome

When testing a special dye is added to the blood sample. Conjugated bilirubin that is water soluble reacts directly to the addition of dyes and changes color.

Unconjugated bilirubin, however is insoluble in water. It changes color only after alcohol is added to the solution. Thus unconjugated bilirubin is known as ‘indirect’ bilirubin and its conjugated form as ‘direct’ bilirubin. (1)

Genes and Gilbert’s syndrome

Gilbert’s syndrome is hereditary. Genes determine the making of all proteins in the body. Essentially these are the blueprints for enzymes and protein formation in the body.

In Gilbert’s syndrome there is a faulty gene that codes for the UGT enzyme. This means bilirubin is not converted at the normal rate to its conjugated form. Thus the unconjugated form builds up in the bloodstream and causes jaundice.

In individuals diagnosed as having Gilbert’s Syndrome, the hepatic bilirubin glucuronidation activity in fact is found to be approximately 30% lower than normal.

How many people does Gilbert’s syndrome affect?

About 1 in 20 people has Gilbert’s syndrome. However, 1 in 3 people who have it will not be aware of it since the disease may be mild in most individuals.

It is more common in men than in women although it affects both sexes equally. It is often first diagnosed in the late teens or early twenties.

Other causes of Gilbert’s syndrome

There are no other causes of getting Gilbert’s syndrome. It is not related to any lifestyle habits or associated with any specific environmental toxin or pollution. (1-6)

Further Reading

Last Updated: Aug 23, 2023

Dr. Ananya Mandal

Written by

Dr. Ananya Mandal

Dr. Ananya Mandal is a doctor by profession, lecturer by vocation and a medical writer by passion. She specialized in Clinical Pharmacology after her bachelor's (MBBS). For her, health communication is not just writing complicated reviews for professionals but making medical knowledge understandable and available to the general public as well.


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