What is Gilbert's syndrome?

From the Guidelines

Gilbert's syndrome is a benign hereditary disorder that reduces the enzyme glucuronosyltransferase's activity, leading to a transient increase in unconjugated bilirubin levels that does not require further management. This condition is a common, mild genetic liver disorder where the liver doesn't process bilirubin properly, causing occasional mild jaundice (yellowing of the skin and eyes) 1. It affects about 5% of the population and is typically harmless, requiring no treatment. The condition occurs due to a mutation in the UGT1A1 gene, which reduces the liver's ability to convert bilirubin into a water-soluble form that can be excreted. Bilirubin levels may increase during times of stress, fasting, dehydration, illness, or intense exercise. Despite the occasional yellowing, Gilbert's syndrome doesn't cause liver damage or affect liver function. Most people with this condition live normal, healthy lives without complications or the need for dietary restrictions. No medications are needed to manage Gilbert's syndrome, though patients should inform healthcare providers about their condition to avoid unnecessary testing when mild jaundice appears.

Some key points to consider about Gilbert's syndrome include:

• It is a benign condition that does not require treatment 1
• It can cause occasional mild jaundice, but does not affect liver function or cause liver damage
• Bilirubin levels may increase during times of stress, fasting, dehydration, illness, or intense exercise
• Patients with Gilbert's syndrome can fast during Ramadan with regular follow-up of their bilirubin level 1
• The condition is caused by a mutation in the UGT1A1 gene, which reduces the liver's ability to convert bilirubin into a water-soluble form that can be excreted.

Overall, Gilbert's syndrome is a harmless condition that does not require treatment or dietary restrictions. Patients with this condition should inform their healthcare providers about their condition to avoid unnecessary testing when mild jaundice appears.

From the Research

Definition and Characteristics of Gilbert's Syndrome

• Gilbert's syndrome is a benign condition characterized by asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation 2.
• It is often familial and is associated with a decrease in hepatic activity of bilirubin-UDP-glucuronosyltransferase to levels around 30% of the normal 3.
• The syndrome is typically marked by intermittent indirect bilirubin elevation 4.

Diagnostic Tests and Biomarkers

• Diagnostic tests for Gilbert's syndrome include the rifampicin test and caloric restriction test, which are non-invasive and can help avoid liver biopsy 3.
• The UGT1A1*28 promoter polymorphism is a biomarker of Gilbert syndrome, and genotyping the UGT1A1 promoter can help determine the etiology of free hyperbilirubinemia of unknown origin 5.

Clinical Significance and Potential Benefits

• Gilbert's syndrome has been considered a physiological abnormality, but recent evidence suggests that individuals with the syndrome may benefit from the mild hyperbilirubinemia and are protected from certain diseases, such as cardiovascular diseases, certain cancers, and autoimmune or neurodegenerative diseases 6.
• The syndrome may have implications for drug metabolism and tolerance, particularly in individuals with the UGT1A1*28/*28 genotype 5.