Benign condition characterized by recurrent episodes of jaundice.
Autosomal recessive
M/C inherited disorder of bilirubin metabolism leading to decreased glucuronidation of bilirubin
History
Gilbert’s syndrome was first described by French gastroenterologist Augustin Nicolas Gilbert and co-workers in 1901.
Augustin Nicolas Gilbert (1858–1927) was a French physician.
Pathophysiology
Bile pigment metabolism – from heme to bilirubin (modified according to Wagner et al. [33 Wagner KH, Wallner M, Molzer C, et al. Looking to the horizon: the role of bilirubin in the development and prevention of age-related chronic diseases. Clin Sci. 2015;129:1–25.[Crossref], [PubMed], [Web of Science ®], , [Google Scholar]]). Hemoglobin is cleaved to yield globin and heme. Heme is enzymatically converted to biliverdin by liberating iron, via oxidation of its α-methene bridge, with loss of a carbon atom (CO). This opens the porphyrin ring, forms the open-chain, linear tetrapyrrole biliverdin, which yields bilirubin after enzymatic reduction of biliverdin’s central methine bond. In the liver, bilirubin is conjugated to enable excretion into the bile, requiring the enzymes UGT1A1 (conjugation) and MRP2 (excretion into the bile). HO: heme oxygenase; BLAVR: biliverdin reductase; UGT1A1: uridine glucuronosyl transferase 1A1; MRP2: multi-drug resistance protein-2. | Shiels, R. G., Lang, C. A., Seyed Khoei, N., & Bulmer, A. C. (2018). Diagnostic criteria and contributors to Gilbert’s syndrome AU – Wagner, Karl-Heinz. Critical Reviews in Clinical Laboratory Sciences, 55(2), 129–139. https://doi.org/10.1080/10408363.2018.1428526
UGT1A1:
Enzyme responsible for conjugation of glucuronic acid with bilirubin for the metabolism of bilirubin
10-35% reduction in the UGT1A1 enzyme activity. Patients manifest this syndrome only when they are generally homozygous for this mutation
