Editors

FredrikÅberg

Gilbert's Syndrome

This benign disorder presenting as asymptomatic jaundice should be identified in order to avoid unnecessary extensive examinations and referrals to hospital.

Gilbert's syndrome is a group of inherited disorders of bilirubin metabolism with an autosomal inheritance pattern essentially characterized by an increase in serum unconjugated bilirubin and intermittent jaundice.
The disorder is caused by defective conjugation of bilirubin in the liver due to a UGT1A1 gene mutation and consequently decreased clearance of bilirubin without other signs of liver failure or haemolysis.
The condition is a benign normal variant not causing any other symptoms apart from jaundice.
Jaundice is usually first observed at the age of 15-30 years, typically in association with some transient condition raising bilirubin levels (such as fasting, physical exertion, infection or alcohol consumption).
Some variants are inherited as an autosomal dominant trait, in which case Gilbert's syndrome occurs in several family members.

The diagnosis can be made in primary health care if all of the following criteria are fulfilled:
- clinical jaundice or randomly increased bilirubin concentration (usually below 70 µmol/l)
- conjugated bilirubin normal or below 30% of total bilirubin
- other liver values normal (ALT, AST, ALP, GT)
- haemolysis tests normal (Hb, reticulocytes, haptoglobin).
In unclear cases, blood tests should be repeated once after 6-12 months.
Upper abdominal ultrasonography is indicated only if other liver disease is suspected.
Liver biopsy is not necessary.

Diseases of the biliary ducts (usually abnormalities in the liver function tests); see also Assessing a patient with an abnormal liver function test results Assessing a Patient with an Abnormal Liver Function Test Result
Haemolysis
Haematoma
Hepatotoxic medications
Crigler-Najjar syndrome http://www.orpha.net/en/disease/detail/205/
- Very rare
- Bilirubin typically 100-300 µmol/l, and jaundice usually appears in childhood
- Diagnosed by a gene test
Dubin Johnson syndrome http://www.orpha.net/en/disease/detail/234 or Rotor syndrome http://www.orpha.net/en/disease/detail/3111
- Very rare
- Conjugated bilirubin > 50% of total bilirubin
Hypercarotenemia
- Excess of dietary carotene (from carrots, for example) will discolour the skin yellow but leave the sclera white. Bilirubin levels are normal.

The disorder is benign. There is no need for treatment, advice on lifestyle or follow-up.
Most drugs with elimination depending on bilirubin conjugation can be used for patients with Gilbert's syndrome but the reduced UGT1A1 activity associated with the syndrome is significant for some rarely used types of medication (such as irinotecan or atazanavir).
It has been suggested that antioxidative effects of bilirubin and its effect on intracellular signalling pathways may protect patients with Gilbert's syndrome against cardiovascular disease, certain types of cancer and autoimmune diseases, but the syndrome may also be associated with an increased risk of gallstones.

Vítek L, Tiribelli C. Gilbert's syndrome revisited. J Hepatol 2023;79(4):1049-1055. [PubMed]