General: People with Gilbert's syndrome are born with a mutated gene. Normally, this gene provides the body with instructions on how to produce an enzyme called bilirubin-uridine diphosphate glucuronyl transferase (bilirubin-UGT). This enzyme breaks down bilirubin, a waste product from red blood cells in the liver. When a person inherits the mutated gene, the body does not produce enough of bilirubin-UGT, and high amounts of bilirubin build up in the bloodstream instead of being excreted from the body.

Some experts believe that Gilbert's syndrome is simply a normal variation in the range of bilirubin levels.

Inheritance: Gilbert's syndrome is passed down among families. The mutated gene that causes Gilbert's syndrome is inherited as an autosomal dominant trait. This means that if one parent has the disorder, there is a 50% chance that his/her child will have Gilbert's syndrome. If both parents have the disorder, there is a 75% chance that the child will inherit the condition.

Factors that worsen symptoms: Several factors may worsen symptoms of Gilbert's syndrome by slightly increasing the amount of bilirubin in the blood. Examples include illnesses or infections (e.g. the common cold or the flu), fasting or skipping meals, menstruation, dehydration, or overexertion.

Gilbert's syndrome is strongly suspected after a blood test. Patients with the condition will have more than 0.3-1.9 milligrams of total bilirubin per deciliter of blood and more than 0-0.3 milligrams of direct bilirubin per deciliter of blood. However, levels of bilirubin normally fluctuate throughout the day. Therefore, if Gilbert's syndrome is strongly suspected based on the person's symptoms, but initial results are normal, repeat testing may be recommended at a different time of day.

If patients have high levels of bilirubin in their blood, a doctor may recommend additional tests to make sure the patient does not have a more serious liver condition. Once other liver conditions are ruled out, Gilbert's syndrome can be diagnosed.

Gilbert's syndrome rarely causes any symptoms. Even if symptoms are present, the condition is still considered harmless. When bilirubin builds up in the blood, some patients may experience episodes of mild jaundice, which causes the skin and eyes to appear yellow in color. Usually the whites of the eyes start to turn yellow before the skin starts to change color.

Although some patients experience periods of fatigue and abdominal pain, it is unclear if they are related to Gilbert's syndrome.

Patients with Gilbert's syndrome have low levels of a liver enzyme called bilirubin-uridine diphosphate glucuronyl transferase (bilirubin-UGT). People with low levels of bilirubin-UGT may experience increased side effects of certain medications, especially an anti-cancer (or antineoplastic) drug called irinotecan (Camptosar®). This is because bilirubin-UGT helps the body process medications. Therefore, patients should talk to their doctors before taking any new medications (prescription or over-the-counter), herbs, or supplements.