Gilbert's syndrome is inherited in an autosomal recessive manner, which means that for symptoms to appear, a person must receive the mutant gene from both parents. The gene responsible for the development of the disease is called UGT1A1. This gene encodes the enzyme uridine diphosphate-glucuronosyltransferase, which is involved in the conversion of unconjugated (free) bilirubin into a water-soluble form, conjugated bilirubin, which is excreted in bile. When the gene is mutated, the activity of the enzyme decreases, and bilirubin accumulates in the blood, causing the characteristic yellowing of the skin and sclera.
In some carriers of the mutant gene, the symptoms of the disease may not appear at all, while in others, even minimal stress, physical overexertion, infectious diseases, or fasting can trigger an exacerbation. Therefore, heredity plays an important, but not the only, role in the development of the clinical picture.
In families where both parents are carriers of the defective gene, the likelihood of having a child with Gilbert's syndrome is 25%. Diagnosing Gilbert's syndrome is a sequential process that includes both clinical evaluation and laboratory methods. The doctor primarily pays attention to episodic jaundice in the absence of other liver disease symptoms, such as pain, enlarged liver, or impairment of its function. It is important to rule out viral hepatitis, hemolytic anemias, and other diseases that may cause a similar clinical picture.
What role does the bilirubin level play in disease diagnosis and the benefit of genetic analysis?
The main laboratory marker of Gilbert's syndrome is an elevated level of unconjugated bilirubin in the blood serum, while ALT, AST, alkaline phosphatase, and complete blood count remain normal. In this case, bilirubin levels rarely exceed 80–100 µmol/L. An additional diagnostic test can be fasting or administration of nicotinic acid, during which bilirubin levels temporarily increase. However, such tests are used less frequently nowadays due to the advent of molecular genetic diagnostic methods.
Genetic testing for a mutation in the UGT1A1 gene is the most accurate method for confirming the diagnosis. It not only allows for the detection of the disease but also helps determine carrier status, which is especially important when planning a family.
The most common mutation is the (TA)7 polymorphism in the gene's promoter region (UGT1A1 *28), which reduces enzyme expression. Modern laboratories offer the option to perform this test using a standard blood sample or even saliva. Despite the benign nature of Gilbert's syndrome, making an accurate diagnosis is important to rule out other conditions and avoid unnecessary medical interventions.
Patients with a confirmed diagnosis are advised to maintain a healthy lifestyle, avoid prolonged fasting, excessive physical exertion, and unnecessary medications that are metabolized in the liver. Regular monitoring and follow-up with a gastroenterologist are usually not required if there are no complications.