What is Gilbert's disease (a genetic disorder characterized by mildly elevated levels of unconjugated bilirubin)?

From the Guidelines

Gilbert's syndrome is a benign condition that does not require specific treatment, and individuals with this condition can be reassured that it does not cause health problems or liver damage. This condition is caused by a mutation in the UGT1A1 gene, which reduces the liver's ability to process bilirubin, leading to mild, fluctuating elevations in bilirubin levels in the blood 1. People with Gilbert's syndrome may occasionally notice mild yellowing of the eyes or skin (jaundice) during periods of stress, illness, fasting, or intense exercise, but these episodes are temporary and resolve on their own. To manage symptoms during flare-ups, it's helpful to maintain regular meals, stay well-hydrated, get adequate rest, and avoid excessive alcohol.

Key Points

• Gilbert's syndrome is a common, harmless genetic liver condition that affects about 3-7% of the population 1.
• The condition is caused by a mutation in the UGT1A1 gene, which reduces the liver's ability to process bilirubin by about 30% 1.
• No specific treatment is required for Gilbert's syndrome, and individuals with this condition can be reassured that it does not cause health problems or liver damage 1.
• Gilbert's syndrome is typically diagnosed through blood tests showing elevated unconjugated bilirubin with otherwise normal liver function 1.
• Despite the occasional jaundice, Gilbert's syndrome is considered a benign condition with an excellent prognosis and normal life expectancy 1.

Diagnosis and Management

• Diagnosis of Gilbert's syndrome should be determined by calculating the proportion of conjugated bilirubin, which should be less than 20%-30% of the total bilirubin, in the absence of haemolysis 1.
• Genetic testing for DNA mutations of uridine 5'-diphospho-glucuronyl-transferase should be considered for definitive confirmation, especially when total bilirubin elevations occur in combination with elevated ALP and aminotransferases 1.
• To manage symptoms during flare-ups, it's helpful to maintain regular meals, stay well-hydrated, get adequate rest, and avoid excessive alcohol.

Prognosis

• Gilbert's syndrome is considered a benign condition with an excellent prognosis and normal life expectancy 1.
• Individuals with Gilbert's syndrome can be reassured that it does not cause health problems or liver damage 1.

From the Research

Definition and Characteristics of Gilbert's Disease

• Gilbert's disease is a common autosomal dominant hereditary condition with incomplete penetrance, characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis 2.
• It is caused by a mutation of the specific UDP glucuronosyl transferase conjugating bilirubin with glucuronic acid, resulting in a reduced activity of this enzyme 3.
• The most common genotype of Gilbert's disease is the homozygous polymorphism A(TA)7TAA in the promoter of the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1), which is a TA insertion into the promoter designated UGT1A1*28 2.

Diagnosis of Gilbert's Disease

• The diagnostic role of the reduced caloric intake test and phenobarbitone treatment in Gilbert's syndrome was evaluated, and it was found that these tests have low diagnostic specificity in Gilbert's syndrome when the differential diagnosis is that of hepatitis 4.
• A rifampicin test may be used in the diagnosis of suspected Gilbert's syndrome instead of a fasting test, as it is simpler and more practical, but its specificity for Gilbert's syndrome is not sufficient 5.
• Molecular genetic tests can now be performed when there is a diagnostic problem, and genetic testing may be necessary in some cases to rule out other metabolism diseases 2, 6.

Clinical Presentation and Management

• Gilbert's disease is considered a rather benign disorder without necessity of any therapeutic intervention 3.
• Patients with Gilbert's disease may present with asymptomatic sporadic episodes of jaundice, due to a mild unconjugated hyperbilirubinemia caused by a deficiency in bilirubin glucoronidation 6.
• Bilirubin levels higher than 6 mg/dL in Gilbert's syndrome are rare, and hemolytic and other metabolism diseases must be ruled out 6.
• The clinical diagnosis of Gilbert's syndrome can be established with relative certainty if the patients have a mild hyperbilirubinemia with a high fraction of unconjugated bilirubin, normal values of liver enzymes, and no overt signs of hemolysis 4.