What is Gilbert's syndrome?

Gilbert’s syndrome is an inherited condition where people cannot get rid of bilirubin as efficiently as they should. Bilirubin is a breakdown product formed when the body recycles the components of dead red blood cells.

In most cases, it produces no serious symptoms but people who have it sometimes report feeling tired, vaguely ill and have niggling health problems. However, these symptoms are very non-specific and can occur in many conditions. Gilbert’s syndrome can lead to occasional episodes of noticeable jaundice, but most people have no symptoms and the blood abnormalities are only noticed in blood tests.

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Gilbert's syndrome and bilirubin excretion

Red blood cells don’t live very long; 120 days on average. When they die, the molecules that make them are reused by the body, so each red blood cell needs to be broken down. Not everything can be reused. Some molecules that are formed during this breakdown need to leave the body to prevent them building up to dangerous levels.

One such waste product is bilirubin. This is formed when haemoglobin, the oxygen-carrying molecule in red blood cells, is taken apart. If you have Gilbert’s syndrome, a mutation in the gene coding for one of your liver enzymes means that bilirubin cannot be processed properly, so its levels can start to rise.

The normal process of bilirubin breakdown has several stages:

When a red blood cell reaches 120 days old, its haemoglobin is broken down into:

  • Haem, a waste product.
  • Globin, a protein that is then recycled.

Haem is then broken down to produce bilirubin, a fat-soluble yellow-orange pigment.

Bilirubin is transported to the liver where it binds to specific proteins to make it water-soluble. This reaction is controlled by the enzyme uridine diphosphate glucuronyl transferase (UGT).

The liver then sends the soluble bilirubin into the bile to pass down the gut and to eventually leave the body in the faeces.

In Gilbert’s syndrome, the UGT gene is defective, so the liver’s capacity to make bilirubin water-soluble is reduced by 60-70%. A backlog of free bilirubin can then build up, causing its levels in the blood to be higher than normal on occasion. This is when symptoms can appear.

Gilbert’s syndrome and jaundice

Serum bilirubin levels in people with Gilbert’s syndrome are often within normal limits or just slightly above them. If they rise, this can cause episodes of jaundice, when the skin and whites of the eyes become slightly yellow because of the extra pigment.

Studies of people with Gilbert’s syndrome also reveal they are particularly prone to vague symptoms such as extreme tiredness, headaches, dizziness and nausea, stomach and abdominal discomfort. They often experience anxiety symptoms and insomnia. All of these symptoms occur in most people at some time, so it is difficult to know how they are actually related to the syndrome.

Jaundice, the only symptom that can be definitely associated with Gilbert’s syndrome, is usually triggered by some type of physiological stress such as strenuous physical exertion or sleep deprivation. Extreme emotional stress such as a bereavement or major life crisis can also bring on an episode of jaundice. Other trigger events in Gilbert’s syndrome include:

  • Vomiting repeatedly
  • Infection with a virus, or other infectious agent
  • Menstruation (usually very heavy periods)
  • Starvation
  • Dehydration
  • Surgery.

Someone with Gilbert’s syndrome finds it much harder to recover from such stresses and they can then experience extreme tiredness and a worsening of the other vague symptoms described above.

How common is Gilbert’s syndrome?

In Western Europe, about 5-10% of people in the general population may have Gilbert’s syndrome but one in 3 of them are completely unaware of it. Estimates for the rest of the world vary because of differences in how it is defined and diagnosed. Gilbert’s syndrome is more common in men and often first diagnosed in young adults.

Living with Gilbert’s syndrome

Jaundice and Gilbert’s syndrome do not damage the liver or have other consequences so there is no treatment that can be justified. Living with the syndrome is a matter of managing your lifestyle so that you feel as well as possible most of the time.

It is sensible to avoid the factors that trigger a jaundice episode, although this is not always possible. If you get flu or an attack of gastroenteritis you then need to take care not to overdo things and to rest and take fluids until your body has dealt with the infection and any episode of jaundice is over.

Do not ignore jaundice that is more serious than usual or lasts for longer as this may be due to a secondary problem that needs investigation and treatment.

Gilbert’s syndrome: things to avoid

Someone with a defect UGT enzyme should avoid drugs that inhibit the UGT enzyme or that are metabolised in the liver in the same pathway used to process bilirubin. The main ones include:

  • Atazanavir (Reyataz®) and indinavir (Crixivan®), which are both used to treat HIV infection.
  • Gemfibrozil (Lopid®), a drug used to lower cholesterol.
  • Irinotecan (Camptosar®), a drug used to treat advanced bowel cancer.

Statins are only partly metabolised by the UGT so they are safe in most people with Gilbert’s syndrome.

Although paracetamol is also partly metabolised by UGT, some people with Gilbert’s syndrome do remove it more slowly from the body, so it may be better to use another pain killer when necessary.

People known to have this syndrome also report a greater intolerance to alcohol; if they overdo drinking they end up with exceptionally severe hangovers.

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