Gilbert's Syndrome

Synonym: Familial non-haemolytic hyperbilirubinaemia, constitutional hepatic dysfunction

Prevalence is estimated at 3-8%.² The worldwide prevalence of Gilbert syndrome varies considerably depending on which diagnostic criteria are used.

Genetic lesions of the bilirubin conjugating enzyme uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1) cause both Gilbert's and the much rarer Crigler-najjar syndromes.^3,4

• Hepatic glucuronidation (necessary for conjugating bilirubin) is reduced to around 30% of normal.
• In addition to their reduced Bilirubin-UGT enzyme activity, most patients with Gilbert's syndrome may have abnormalities in the glucuronidation of aspirin or derivatives of coumarin and dopamine.⁵

It can remain unnoticed for many years, but usually presents in adolescence with:

• Intermittent jaundice noticed after fasting, lack of sleep, vigorous exercise or during an intercurrent illness.⁶
• Exposure to certain medications may precipitate jaundice e.g. chemotherapy. Adverse effects of anticancer agents have been observed in Gilbert's patients due to reduced drug or bilirubin glucuronidation.⁷
• Gilbert's syndrome is a determining factor for neonatal hyperbilirubinaemia ABO incompatibility.⁸

Other typical findings include:

• Jaundice
• Nausea
• Fatigue
• Shakiness
• Bowel complaints
• Vomiting
• Difficulty concentrating

Haemolytic anaemias:

• Hereditary spherocytosis
• Congenital dyserythropoietic anaemia type 2

Crigler-Najjar syndrome types I or II

Full blood count shows normal reticulocyte count - to distinguish from haemolysis.
Gilbert syndrome patients tend to have total serum bilirubin levels from 17-100 μmol/L.⁹

• A rise in bilirubin on fasting or after IV nicotinic acid can confirm the diagnosis.¹⁰
• Other liver function tests (including lactate dehydrogenase) and liver biopsy are normal, but the latter should rarely be required clinically.
• There is no bilirubin and subnormal amounts of urobilinogen in the urine.

This is excellent. No treatment is required and life expectancy is normal.