Online consultations with MCSC doctors n. a. A. S. Loginov

Gilbert's Syndrome

Gilbert's Syndrome (SJ) – this is a hereditary disease associated with a violation of the capture and connection of bilirubin in hepatocytes. 

Thanks to the filtering function of the liver, which is present in any healthy person, there is a synthesis of bile, necessary for the breakdown of proteins, fats, carbohydrates, neutralization and elimination of toxic substances.

In patients with FH, the liver is not able to fully process and remove the toxic bile pigment – bilirubin from the body.

This is due to the reduced activity of a specific enzyme: uridine diphosphate (UDP). 

Symptoms:

  • Jaundice with periodic deterioration on the background of physical stress, errors in the diet, mental stress, starvation
  • An increase in the total billirubin in the biochemical blood test due to the indirect fraction
  • Nausea, bitterness in the mouth, bloating
  • Depressed mood, fatigue, poor sleep
  • Itching of the skin without visible rashes on the skin

Why does Gilbert's Syndrome occur?

This condition is caused by a mutation in the UGT1A1 gene, which encodes the UDP-glucuronyltransferase enzyme. As a result of the violation of the enzyme, free bilirubin accumulates in the blood and leads to the staining of the sclera, mucous membranes and skin in yellow.

Most often, this disease is diagnosed in men and first manifests itself in adolescence and adolescence, as there is a change in the metabolism of bilirubin under the influence of sex hormones.

During the biochemical analysis, an isolated increase in bilirubin is observed (From 8.5 to 20.5 mmol/l) at the expense of its indirect fraction.

Bilirubin is a product of the natural breakdown of hemoglobin, during the renewal of red blood cells. To remove it from the body, the enzyme uridine diphosphate-glucuronyltransferase A1 (UDPHT) is required, its activity is regulated by a section of the gene (promoter region) located on the 2nd pair of chromosomes (2q37). With an increase in the formation of bilirubin by the body, this site normally stimulates the production of the UDPHT enzyme, and bilirubin is excreted from the body. Some people in this zone have a hereditary mutation in the area of the so-called TA repeats, instead of 6 of 7. In this situation, the increase in the production of the UDPHT enzyme in response to an increase in the formation of bilirubin by the body does not occur, and it is delayed, which we can see from the biochemical parameters of the blood.

To date, the MCSC can conduct a molecular genetic study of this site using a polymerase chain reaction to clarify the diagnosis.

With the variant of 7/7 TA repeats, we can confidently talk about Gilbert's syndrome (about 10 % of the population)

In the variant 6/7 TA repeats, the mutation is present only in one chromosome (30-40 % of the population) and the decrease in the activity of the enzyme is not so pronounced, however, in such patients, an increase in bilirubin can be detected (as a rule, rarely above 30 micromol/l). In this case, the diagnosis of Gilbert's syndrome can also be made, but only by the attending physician based on the totality of the general examination data.

In the case of variant 6/6 (50-60% of the population), according to the study, it is impossible to diagnose Gilbert's syndrome. Additional examination is required. The increase in bilirubin can be caused by other mutations in the UDPHT gene (a more complex study is required-gene sequencing) causing another similar disease, Krigler-Nayar syndrome.

In rare cases, 8 TA repeats can occur in the promoter region of UDPHT, the characteristics of bilirubin exchange in this case correspond to the defect of 7 TA repeats. 

In the laboratory of the center for personalized medicine, you can donate blood for DNA diagnostics of disorders in the promoter region of the UGT1A1 gene and get recommendations from a geneticist if you suspect the presence of Gilbert's Syndrome.

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