Gilbert's syndrome overview

Gilbert’s syndrome (pr. Zhil-bear), often shortened to the acronym GS, is the most common hereditary cause of increased bilirubin, and is found in up to 5% of the population. The main symptom is otherwise harmless jaundice which does not require treatment, caused by elevated levels of unconjugated bilirubin in the bloodstream (hyperbilirubinemia).

The source of this hyperbilirubinemia is reduced activity of the enzyme glucuronyltransferase which conjugates bilirubin and some other lipophilic molecules. Conjugation renders the bilirubin water-soluble and suitable for excretion via the kidneys.

Gilbert’s syndrome was first described by French gastroenterologist Augustin Nicolas Gilbert and co-workers in 1901.^[1][2] In German literature, it is commonly associated with Jens Einar Meulengracht.^[3]

Gilbert’s syndrome is caused by approximately 30%-50% reduced glucuronidation activity of the enzyme Uridine-diphosphate-glucuronosyltransferase isoform 1A1 (UGT1A1).^[4][5] The gene which encodes UGT1A1 normally has a promoter region TATA box containing the allele A(TA₆)TAA. Gilbert’s syndrome is associated with homozygous A(TA₇)TAA alleles.^[6] The allele polymorphism is referred to as UGT1A1*28.

Gilbert’s syndrome affects up to 10% of people in some Caucasian populations. The condition is usually noncancerous (benign).