What is Gilbert syndrome
Gilbert’s syndrome is a lifelong disorder. However, it doesn’t require treatment because it doesn’t pose a threat to your health and doesn’t cause complications or an increased risk of liver disease. Episodes of jaundice and any associated symptoms are usually short-lived and eventually pass.
People with Gilbert’s syndrome have a faulty UGT1A1 gene which causes the liver to have problems removing bilirubin from the blood. The UGT1A1 gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which is found primarily in liver cells and is necessary for the removal of bilirubin from the body.
Normally, when red blood cells reach the end of their life (after about 120 days), hemoglobin – the red pigment that carries oxygen in the blood – breaks down into bilirubin. The liver converts bilirubin into a water-soluble form, which passes into bile and is eventually removed from the body in urine or stools. Bilirubin gives urine its light yellow color and stools their dark brown color.
Figure 1. Normal bilirubin formation and metabolism
Note: BM = bone marrow; RBC = red blood cell
In Gilbert’s syndrome, the faulty gene means that bilirubin isn’t passed into bile (a fluid produced by the liver to help with digestion) at the normal rate. Instead, it builds up in the bloodstream, giving the skin and white of the eyes a yellowish tinge.
Other than inheriting the faulty gene, there are no known risk factors for developing Gilbert’s syndrome. Gilbert’s syndrome isn’t related to lifestyle habits, environmental factors or serious underlying liver problems, such as cirrhosis, hepatitis B or hepatitis C.
Gilbert syndrome is a common condition that is estimated to affect 3 to 7 percent of Americans. Gilbert’s syndrome affects more men than women. Gilbert syndrome is usually diagnosed during a person’s late teens or early twenties. If people with Gilbert syndrome have episodes of hyperbilirubinemia, these episodes are generally mild and typically occur when the body is under stress, for instance because of dehydration, prolonged periods without food (fasting), illness, vigorous exercise, or menstruation. Some people with Gilbert syndrome also experience abdominal discomfort or tiredness. However, approximately 30 percent of people with Gilbert syndrome have no signs or symptoms of the condition and are discovered only when routine blood tests reveal elevated unconjugated bilirubin levels.
What triggers Gilbert syndrome symptoms?
People with Gilbert’s syndrome often find there are certain triggers that can bring on an episode of jaundice.
Some of the possible triggers linked with the condition include:
- being dehydrated
- going without food for long periods of time (fasting)
- being ill with an infection
- being stressed
- physical exertion
- not getting enough sleep
- having surgery
- in women, having their monthly period
Where possible, avoiding known triggers can reduce your chance of experiencing episodes of jaundice.
Other names for Gilbert syndrome
- Constitutional liver dysfunction
- Familial nonhemolytic jaundice
- Gilbert disease
- Gilbert-Lereboullet syndrome
- Gilbert’s disease
- Gilbert’s syndrome
- Hyperbilirubinemia 1
- Meulengracht syndrome
- Unconjugated benign bilirubinemia
Gilbert syndrome outlook (prognosis)
Jaundice may come and go throughout life. It is more likely to appear during illnesses such as colds. Gilbert’s syndrome does not cause health problems. However, it can confuse the results of tests for jaundice.
Gilbert syndrome possible complications
The low level of the bilirubin-processing enzyme that causes Gilbert’s syndrome may also increase the side effects of certain medications, since this enzyme plays a role in helping clear these medications from your body.
These medications include:
If you have Gilbert’s syndrome, talk to your doctor before taking new medications. Also, having certain types of Gilbert’s syndrome may increase your risk of developing gallstones.
Gilbert’s syndrome causes
Gilbert’s syndrome is a genetic disorder that’s hereditary (it runs in families). People with Gilbert’s syndrome have a faulty UGT1A1 gene which causes the liver to have problems removing bilirubin from the blood. The UGT1A1 gene provides instructions for making the bilirubin uridine diphosphate glucuronosyltransferase (bilirubin-UGT) enzyme, which is found primarily in liver cells and is necessary for the removal of bilirubin from the body.
The bilirubin-UGT enzyme performs a chemical reaction called glucuronidation. During this reaction, the enzyme transfers a compound called glucuronic acid to unconjugated bilirubin, converting it to conjugated bilirubin. Glucuronidation makes bilirubin dissolvable in water so that it can be removed from the body.
Gilbert syndrome occurs worldwide, but some mutations occur more often in particular populations. In many populations, the most common genetic change that causes Gilbert syndrome (known as UGT1A1*28) occurs in an area near the UGT1A1 gene called the promoter region, which controls the production of the bilirubin-UGT enzyme. This genetic change impairs enzyme production. However, this change is uncommon in Asian populations, and affected Asians often have a mutation that changes a single protein building block (amino acid) in the bilirubin-UGT enzyme. This type of mutation, known as a missense mutation, results in reduced enzyme function.
People with Gilbert syndrome have approximately 30 percent of normal bilirubin-UGT enzyme function. As a result, unconjugated bilirubin is not glucuronidated quickly enough. This toxic substance then builds up in the body, causing mild hyperbilirubinemia.
Not everyone with the genetic changes that cause Gilbert syndrome develops hyperbilirubinemia, indicating that additional factors, such as conditions that further hinder the glucuronidation process, may be necessary for development of the condition. For example, red blood cells may break down too easily, releasing excess amounts of bilirubin that the impaired enzyme cannot keep up with. Alternatively, movement of bilirubin into the liver, where it would be glucuronidated, may be impaired. These other factors may be due to changes in other genes.
Gilbert syndrome can have different inheritance patterns. When the condition is caused by the UGT1A1*28 change in the promoter region of the UGT1A1 gene, it is inherited in an autosomal recessive pattern, which means both copies of the gene in each cell have the mutation. The parents of an individual with an autosomal recessive condition each carry one copy of the mutated gene, but they typically do not show signs and symptoms of the condition.
When the condition is caused by a missense mutation in the UGT1A1 gene, it is inherited in an autosomal dominant pattern, which means one copy of the altered gene in each cell is sufficient to cause the disorder. A more severe condition known as Crigler-Najjar syndrome occurs when both copies of the UGT1A1 gene have mutations.
Gilbert syndrome symptoms
Most people with Gilbert’s syndrome experience occasional and short-lived episodes of jaundice (yellowing of the skin and whites of the eyes) due to the build-up of bilirubin in the blood.
As Gilbert’s syndrome usually only causes a slight increase in bilirubin levels, the yellowing of jaundice is often mild. The eyes are usually affected most.
Some people also report other problems during episodes of jaundice, including:
- abdominal (tummy) pain
- feeling very tired (fatigue)
- loss of appetite
- feeling sick
- irritable bowel syndrome (IBS) – a common digestive disorder that causes stomach cramps, bloating, diarrhea and constipation
- problems concentrating and thinking clearly (brain fog)
- a general sense of feeling unwell
However, these problems aren’t necessarily thought to be directly related to increased bilirubin levels, and could indicate a condition other than Gilbert’s syndrome.
Around one in three people with Gilbert’s syndrome don’t experience any symptoms at all. Therefore, you may not realise you have the syndrome until tests for an unrelated problem are carried out.
Gilbert syndrome diagnosis
Gilbert’s syndrome can be diagnosed using a blood test to measure the levels of bilirubin in your blood and a liver function test.
When the liver is damaged, it releases enzymes into the blood. At the same time, levels of proteins that the liver produces to keep the body healthy begin to drop. By measuring the levels of these enzymes and proteins, it’s possible to build up a reasonably accurate picture of how well the liver is functioning.
The combination of normal blood and liver function tests and elevated bilirubin levels is an indicator of Gilbert’s syndrome. No other testing usually is needed, although genetic testing can confirm the diagnosis.
In certain cases, a genetic test may be necessary to confirm a diagnosis of Gilbert’s syndrome.
Gilbert syndrome treatment
Gilbert’s syndrome doesn’t require treatment. The bilirubin levels in your blood may fluctuate over time, and you may occasionally have jaundice, which usually resolves on its on with no ill effects.
Living with Gilbert syndrome
Gilbert’s syndrome is a lifelong disorder. However, it doesn’t require treatment because it doesn’t pose a threat to your health and doesn’t cause complications or an increased risk of liver disease.
Episodes of jaundice and any associated symptoms are usually short-lived and eventually pass.
If you have Gilbert’s syndrome, there’s no reason to modify your diet or the amount of exercise you do, and the recommendations about eating a healthy, balanced diet and the physical activity guidelines still apply.
However, you may find it useful to avoid the things you know trigger episodes of jaundice, such as dehydration and stress.
If you have Gilbert’s syndrome, the problem with your liver may also mean you’re at risk of developing jaundice or other side effects after taking certain medications. Therefore, make sure your doctors know you have Gilbert’s syndrome. Because Gilbert’s syndrome affects the way your body processes certain medications, every doctor you visit needs to know about your condition.
Medications that shouldn’t be taken if you have Gilbert’s syndrome, unless advised by a doctor, include some types of HIV medication, some types of medication for high cholesterol and some chemotherapy medications.