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Gilbert’s syndrome is caused by a mutation in the promoter region of the UGT1A gene that gives instruction to the production of the enzyme glucuronosyltransferase involved in the metabolism of bilirubin, the compound produced through the breakdown of hemoglobin. The UGT1A gene is located at human chromosome 2. The mutation causes the reduction of enzyme activity by approximately 70 to 80 percent, leading to increased bilirubin levels in the blood.
In the liver, glucuronosyltransferase conjugates bilirubin to make it water-soluble so it will be excreted in the bile. Conjugated bilirubin travels to the intestine with bile and mixes with digested food, and is responsible for the characteristic color of stool.
Gilbert’s syndrome is an autosomal recessive disorder. An individual gets Gilbert’s syndrome if he gets two copies of the mutated gene from both of his parents. One copy of the gene may not cause Gilbert’s syndrome but the gene can be transmitted to offspring.
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Signs and Symptoms
There are no obvious symptoms for Gilbert’s syndrome other than mild jaundice, or yellowing of the eyes and skin. Jaundice is a result of the elevated blood levels of unprocessed bilirubin which have a yellowish color. Other reported symptoms include abdominal pain, gastrointestinal problems, fatigue and weakness. It is not clear if these symptoms are related to the increased bilirubin levels in the blood.
Glucuronosyltransferase is also involved in the metabolism of certain drugs. Low amounts of the enzyme can result in increased side effects of the drugs. For example, the cancer chemotherapy drug irinotecan can cause diarrhea to a person with Gilbert’s syndrome if the drug reaches toxic levels.
The symptoms of Gilbert’s syndrome can be mistakenly identified as symptoms of other liver diseases like cirrhosis and hepatitis so laboratory tests should be done to rule out these diseases.
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Gilbert’s syndrome is usually diagnosed accidentally when laboratory tests are ordered for unrelated conditions. The blood bilirubin level of people with Gilbert’s syndrome is more than the normal 1.2 mg/dL.DNA tests can also be used to detect the gene mutation that causes the disorder.Other forms of diagnosis include medical history, physical examination, urine and blood tests.
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Prevalence and Risk Factors
Gilbert’s syndrome affects 5 to 10 percent of the general population. Certain ethnic populations have a higher percentage of affected individuals. Individuals also have an increased risk of developing Gilbert’s syndrome if both parents carry a copy of the defective gene.Symptoms do not appear until puberty when increased sex hormone production alters bilirubin metabolism.
There are factors that may increase the likelihood of symptoms like jaundice. These include dehydration, stress, strenuous exercise, fasting and low calorie diet.
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Gilbert’s syndrome is a mild disorder so it does not usually require treatment. In fact, some specialists do not consider it a disorder. People with the disorder have normal and healthy lives. Some of them have not experienced symptoms at all. The disorder doesn’t affect other important liver functions. Jaundice usually goes away on its own, but if it becomes a problem, medication is available to reduce blood bilirubin levels.