What is Gilbert's syndrome?
Gilbert’s syndrome (GS) is a condition in which you have higher than normal amounts of bilirubin in your blood.
The medical name for this is ‘unconjugated hyperbilirubinemia’. It is also sometimes called familial nonhaemolytic bilirubinaemia or constitutional hepatic dysfunction.
These long names may not sound promising but GS is in fact a harmless condition. It is not a disease and it is possible that you may not even know you have it.
GS is usually discovered by chance when a routine or unrelated blood test reveals a rise in the level of bilirubin in your blood. It is likely you will be told that you have high or raised ‘serum bilirubin’.
This is not a bad thing in isolation, but until GS is specifically diagnosed you may be left to worry whether having high bilirubin is an indication of a more serious liver illness.
Although a benign condition, people do report some ill-effects from GS. These may or may not be related to other problems. This section of the website describes some of the symptoms most commonly mentioned and provides advice on how you might avoid these symptoms occurring.
What is bilirubin?
Bilirubin is a normal by-product of the breakdown of old red blood cells. These contain haemoglobin, an important protein that helps transport oxygen around your body. It is also a pigment that gives red blood cells their colour.
Red blood cells last about 120 days. When they expire the haemoglobin is broken down into haem and globin. Globin is a protein that is stored by the body for later use. Haem (or heme) is waste material that needs to be flushed from the body. The ‘pathway’ or removal process that makes this possible is called glucuronidation.
In this process the heme is broken down into an orangey-yellow pigment known as ‘free’ bilirubin. This is a fat-soluble form of bilirubin that is transported to your liver. Here, bilirubin is metabolised by a liver enzyme called urodine diphosphate glucuronosyltransferase (more easily called UGT) and modified to a water-soluble form. This is known as ‘conjugated’ bilirubin.
This watery version is more easily secreted into bile, a fluid produced by your liver to aid digestion. It travels in the bile through your gall bladder and into your small intestine, where it is converted by bacteria into a variety of pigment substances, primarily urobilinogen. It is eventually excreted from the body in your faeces and urine.
This is how the removal of bilirubin is supposed to work. If you have GS, however, you do not have enough of the UGT enzyme to modify the bilirubin at the normal rate.
This is what causes levels of unmetabolised or ‘unconjugated’ bilirubin to build up in your blood. When testing for bilirubin, a special dye (called a reagent) is added to the blood specimen. Water-soluble conjugated bilirubin will react directly to the addition of dyes by changing colour. Unconjugated bilirubin, which does not dissolve in water, does not react to the dye until alcohol is added to the solution.
For this reason, unconjugated bilirubin is known as ‘indirect’ bilirubin and its conjugated form as ‘direct’ bilirubin. Added together, they are known as your total serum bilirubin.
Who gets Gilbert's syndrome?
GS was first identified by the French doctors Nicolas Augustin Gilbert (after whom it is named) and Pierre Lereboullet in 1900. They described a syndrome of benign, periodic but chronic jaundice occurring without any other symptoms of liver disease.
Today, GS is relatively common. It is thought to affect about one person in 20 or about 4% of the population. Some estimates are higher. It affects both males and females.
GS is thought to be hereditary, meaning that it is caused by a gene that runs in your family.
Genes contain the instructions for making up your body. GS is caused by a variant gene that has a ‘mutation’. A mutation is a permanent change in the code of the DNA making up a gene or chromosome. This can alter the way a physical characteristic is expressed or cause some function in the body to occur differently. Sometimes the word ‘variant’ is used instead of mutation as many changes do not cause any disorder.
In GS the mutation causes ‘reduced gene expression’, meaning that it limits production of thespecific UGT enzyme (called UGT1A1) responsible for conjugating bilirubin.
This mutation has been pinpointed to occur on a gene called the UDP-glucoronosyltransferase gene. Half the general population may have this gene.
However, GS is a ‘recessive’ disorder, meaning that you need to have two copies of the abnormal gene (one from each parent) to acquire it. People who inherit the same mutated gene from both their parents are termed ‘homozygote’. Even so, having two abnormal genes does not necessarily mean that you will go on to develop GS.
Although it is not understood why, some people with only a single abnormal gene (‘heterozygotes’) have higher than usual levels of unconjugated bilirubin but do not have GS.
At present there is no established genetic test for GS.
A significant increase in your bilirubin levels may lead to jaundice. This is a yellowing of the skin and the whites of the eyes. In GS this is seen more in the eyes. As bilirubin levels are usually only slightly increased it is likely to take a medically trained person to observe jaundice in your skin appearance.
Jaundice may become more obvious if you become stressed, ill with an infection (particularly a viral illness), starved or dehydrated – conditions not in themselves related to the disorder. Menstruation might also be a factor in sparking off higher bilirubin levels.
While jaundice is the only recognized clinical symptom, many people with GS report a number of common symptoms or effects they attribute to the disorder. This is why they may have a blood test in the first place. Such symptoms include:
- feeling tired all the time (fatigue)
- loss of appetite
- nausea or dizziness
- abdominal pain
- irritable bowel syndrome (IBS)
- difficulty maintaining concentration
- very dark urine.
Such symptoms appear to occur in varying degrees (and some are common to many liver diseases). At least 30% of people with GS do not show any symptoms at all.
GS is often diagnosed in your late teens and early twenties. In most cases doctors should be able to establish diagnosis on the basis of liver function tests (LFTs) and jaundice, if you have it.
Sometimes – but rarely – a blood test is taken before and after a 48 hour diet in which you are required to reduce your calorie intake. In people with GS a significant increase in their bilirubin levels is usually seen to follow this.
Liver function tests are used to indicate whether your liver is inflamed (hepatitis), damaged or not working properly. They measure levels of certain enzyme and protein substances in your blood that may alter when liver damage is present.
Liver function tests also measure the amount of bilirubin to gain an indication of your liver’s ability to metabolise and secrete it into bile. The ‘serum bilirubin test’ is considered to provide a very accurate picture of how well the liver is functioning.
Raised and heavily unconjugated bilirubin in your blood is abnormal. When this is the only abnormal result, it is seen as a strong indication that you may have GS. Bilirubin levels can, however, fluctuate in GS and it is possible that they can be within the normal range over a period of time.
Bilirubin is measured in micromoles per litre (umol/L). Total serum bilirubin higher than 17 umol/L is outside the normal range.
Where jaundice is evident, medical staff may seek diagnosis by excluding more serious forms of liver disease. GS is one of the most common causes of unconjugated hyperbilirubinemia, but there are others. These include a rare and dangerous disorder called Crigler-Najjar syndrome which is inherited from the same gene.
If your diagnosis involves further testing or delay of some sort you may experience some anxiety before other possibilities can be ruled out.
For this reason it is important that doctors diagnose GS as soon as possible.
Other than inheriting the abnormal gene there are no known risk factors for developing GS. It is not related to any lifestyle habits or caused by any specific environment.
Your doctor should consider the effect of GS when prescribing medicines. Although it is uncommon, there is a possibility that lack of the UGT enzyme can have an effect on the way you respond to certain medications.
Looking after yourself
Having GS should not prevent you leading a normal life in any way.
There are a number of circumstances that are considered likely to cause your bilirubin levels to rise. Some of these cannot be helped but you might manage your situation better if you can avoid the following:
- dieting or fasting
- emotional stress or anxiety
- infectious illnesses
- heavy physical exertion that can leave you feeling drained
- lack of sleep.
It is important that you:
- eat regularly and healthily
- drink plenty of water
- avoid fatty or sugary foods.
Many people find that they cannot tolerate eating carbohydrate foods very well. Typical carbohydrates are bread, pasta, rice and potatoes.
A number of foods, vitamins and supplements are commonly recommended by people with the disorder.
There is no clear agreement about the impact of alcohol on people with GS although a number of people report increased sensitivity to its effects.
In general, any person with a liver condition should approach alcohol with caution.
Please visit the support section of our website for information on Support groups in your area or visit our Useful Links section for other organisations who may be able to offer information and support.
Download: Gilberts Syndrome GSZ/02/18
Reviewed by: Dr Mark Wright, Consultant Hepatologist, Southampton University Hospital Trust.