Gilbert Syndrome

Gilbert syndrome is a benign inherited disorder of reduced bilirubin glucuronidation giving mild intermittent unconjugated hyperbilirubinaemia.

• Prevalence 3 to 10%, male predominance in diagnosis.
• Cause: promoter variant (TA)7 TAA in UGT1A1 (autosomal recessive in Europeans), with UGT1A1 activity reduced to 20 to 30%.
• Bilirubin rises with fasting, illness, stress, exertion, menstruation, dehydration.
• No liver disease, no haemolysis, normal prognosis. Possible protective effect against cardiovascular disease.
• Clinically relevant for drug toxicity (irinotecan, atazanavir, nilotinib, pazopanib).

• Mild intermittent jaundice or scleral icterus, often noticed incidentally.
• Fatigue or abdominal discomfort are reported but not caused by the syndrome.
• Examination is normal, no hepatosplenomegaly.
• Onset typically after puberty.

• Isolated unconjugated hyperbilirubinaemia, usually under 3 mg/dL (up to 6 mg/dL when fasting), with direct fraction under 20%.
• Normal liver enzymes, albumin, INR, haemoglobin, reticulocyte count, haptoglobin and blood film.
• Bilirubin rises by 2 to 3 fold after a 24 to 48 hour 400 kcal fast (provocation test, rarely required).
• Genetic testing for UGT1A1 (TA)7 is confirmatory but unnecessary in typical cases.
• Exclude haemolysis, Crigler Najjar syndrome, liver disease, drug effects (rifampicin, indinavir).

• No treatment needed. Reassure the patient and give written information.
• Avoid prolonged fasting, dehydration and excessive alcohol.
• Drug counselling: reduced glucuronidation raises toxicity of irinotecan (consider dose reduction in homozygotes), and bilirubin rises with atazanavir (not harmful).
• Phenobarbital 60 to 180 mg at night lowers bilirubin but is not indicated.
• No follow up necessary beyond confirming stable pattern. Further investigation if bilirubin exceeds 5 mg/dL, direct bilirubin rises, or enzymes become abnormal.
• Family screening is not required.