Read more about this disease, some with Classification – Types – Signs and symptoms – Genetics – Pathophysiology – Diagnosis – Screening – Prevention – Treatment and management – Cures and much more, some including pictures and video when available.
‘Gilbert’s syndrome, pronounced ‘zheel-BAYR’, often shortened to GS, is the most common hereditary cause of increased bilirubin, and is found in up to 5% of the population (though some gastroenterologists maintain that it is closer to 10%). 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, after which it is excreted in bile into the duodenum.
Gilbert’s syndrome is caused by approximately 70%-75% reduced glucuronidation activity of the enzyme Uridine-diphosphate-glucuronosyltransferase isoform 1A1 (UGT1A1).[1] [2] 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.[3] The allele polymorphism is referred to as UGT1A1*28. In 94% of GS sufferers mutations in two of the other glucoronyltransferase variations UGT1A6 (rendered 50% inactive) and UGT1A7 (rendered 83% ineffective) are also present. Because of its effects on drug and bilirubin breakdown, and because of its genetic inheritence, Gilbert’s syndrome can be classed as a minor inborn error of metabolism.
Gilbert’s syndrome produces an elevated level of unconjugated bilirubin in the bloodstream but normally this has no serious consequence. Mild jaundice may appear under conditions of exertion, stress, fasting, and infections, but the condition is otherwise usually asymptomatic. [4][5]
It has been reported that GS may contribute to an accelerated onset of neonatal jaundice[6].
The enzymes that are defective in GS (UGT1A1) are also responsible for some of the liver’s ability to detoxify certain drugs. For example, Gilbert’s syndrome is associated with severe diarrhea and neutropenia in patients who are treated with irinotecan, which is metabolized by UGT1A1.[7]
[tubepress mode=’tag’, tagValue=’Gilbert’s syndrome’]