Gilbert's syndrome

What is Gilbert's syndrome?

Gilbert's syndrome, or benign congenital intermittent (with periodic exacerbations) hyperbilirubinaemia, is the most common cause of congenital elevated bilirubin. Gilbert's syndrome is not a disease but a congenital metabolic disorder that can lead to elevated blood bilirubin levels. Gilbert's syndrome is not dangerous, its most noticeable symptom is jaundice of different degrees, which does not indicate a serious illness, and is only a temporary cosmetic defect. It does not indicate liver damage, therefore no treatment is required. Some people with this syndrome may not even have jaundice. Gilbert's syndrome occurs in an average of 5–12% of European (Caucasian) population.

The main purpose of diagnosing Gilbert's syndrome is to rule out other serious liver diseases.

Test description

To test Gilbert's syndrome at the GenEra laboratory, the person must submit a so-called “saliva sample” — a smear from the oral mucosa. If the sampling is done by our partner, “Centrālā laboratorija”, then they will take a blood sample. There is no need for hospitalization, which is the case when the standard method for diagnosing Gilbert's syndrome (biochemical urine analysis) is used. Gene-level testing is the most accurate method. Nowadays, this method has become the standard for diagnosing Gilbert's syndrome worldwide.

Cause of Gilbert's syndrome

Gilbert's syndrome is caused by mutations in the gene UGT1A1, which encodes bilirubin-UDP glucuronosyltransferase (UGT). The most common mutation is TA insertion (homozygous) in the promoter region of the UGT1A1 gene. This mutation reduces bilirubin-UDP glucuronosyltransferase production by 30–50%. As bilirubin-UDP glucuronosyltransferase production decreases, blood bilirubin levels rise accordingly, as bilirubin-UDP glucuronosyltransferase is an enzyme involved in the processing of bilirubin.

People with Gilbert's syndrome may have drug intolerance to medicinal products that require bilirubin metabolism (e.g. Irinotecan, Paracetamol, etc.).

Interpretation of results

The most common cause of Gilbert's syndrome is TA insertion in the promoter region of the UGT1A1 gene. In the normal variant, there are six TA repeats in both alleles of the promoter region of the UGT1A1 gene — A (TA) 6TAA, but in the case of Gilbert's syndrome, both alleles contain seven TA repeats — A (TA) 7TAA.

If a patient with elevated blood bilirubin does not have the most common mutation that causes Gilbert’s syndrome, other causes of elevated bilirubin should be sought. In these cases, it also cannot be ruled out that the patient has other mutations in the UGT1A1 gene that are not tested by this test.