1. Gilbert’s syndrome Research Center for Genetic Engineering and Biotechnology “Georgi D. Efremov”, MASA What is Gilbert’s syndrome? Gilbert’s Syndrome is an inherited form of unconjugated hyperbilirubinaemia resulting in mild jaundice occurring in the absence of haemolysis or other underlying liver disease. Typically, total serum bilirubin concentration is between 20 and 50 μmol/L and may be noticeable within the sclera, skin and mucous membranes. The hyperbilirubinaemia is caused by reduced activity of the hepatic 1A1 isoform of the uridine diphosphoglucose glucuronosyltransferase enzyme (UGT1A1), which is responsible for conjugating water insoluble unconjugated bilirubin to glucuronic acid2. It is most often detected during routine blood tests taken during periods of fasting, infection, intense exercise and after surgery. What are the symptoms of Gilbert's syndrome? Usually none. The level of bilirubin in the blood goes up and down. However, this does not usually cause any problems as the level does not go very high. Jaundice. If the level of bilirubin goes above a certain level you become jaundiced (yellowing of the skin and whites of the eyes). This is because bilirubin is an orangy-yellow colour. Some people with Gilbert's syndrome become mildly jaundiced from time to time. This may seem alarming, but is of little concern if the cause is Gilbert's syndrome. The jaundice tends to occur most commonly if you are ill with another problem such as an infection, starvation, repeated vomiting, following surgery or during times of exertion or stress. Genetics The majority of cases of Gilbert’s Syndrome are caused by a polymorphism in the promoter region of the UGT1A1 gene, the A(TA)6TAA element2. The insertion of two extra nucleotides (TA) within this TATA box results in a A(TA)7TAA mutant allele, designated UGT1A1*28. The UGT1A1*28 homozygous genotype is expressed as 7/7 (positive–Gilberts Syndrome) A UGT1A1*28 heterozygous genotype is expressed as 6/7 (carrier) A UGT1A1*28 wildtype is expressed as 6/6 (normal) Since Gilberts Syndrome is autosomal recessive, carriers (6/7 genotype) are not affected. What is the treatment for Gilbert's syndrome? No treatment is needed. People with Gilbert's syndrome normally lead healthy lives. Life expectancy is not affected and life insurance is not affected. Mild jaundice may recur from time to time for short periods, but usually causes no health problems. References Bosma PJ, Chowdhury JR, Bakker C et al. The genetic basis of the reduced expression of bilirubin UDP- glucuronosyltransferase 1 in Gilberts Syndrome. N Eng J Med. 1995. 338; 1171-1175. Diagnosis of Gilbert's syndrome at RCGEB Diagnosis of Gilbert’s syndrome at RCGEB is based on analysis of UGT1A1*28 mutation. Material for testing Full blood samples into sterile tubes with anticoagulant EDTA Epidemiology Gilbert's syndrome is a very common hereditary condition. About 1 in 20 people has this syndrome - but 1 in 3 people who have it will not be aware of it. It is more common in men than in women. It is often first diagnosed in the late teens or early twenties. RCGEB, 2013 Genetics testing for Gilbert's syndromePrice (МКД) Detection of UGT1A1*28 7500