Gilbert's syndrome

From Ganfyd

A common variant of little significance occasionally adding a little colour to life

Some people are genetically determined to have a normal resting bilirubin level higher than most. On stress, such as fasting or minor illness or other causes of an increase in bilirubin production they are likely to develop a tinge of jaundice. The variety with predominantly unconjugated bilirubin is known as Gilbert's syndrome and is usually unimportant.

Liver enzymes are not raised in this variant.

It was first described in 1901 by Augustine Gilbert and Pierre Lereboulette (poor unremembered chap) who were French.[1] The pronunciation therefore is with a soft G.

Aetiology

The enzyme affected is uridine-diphosphoglucuronate glucuronosyltransferase (UGT1A1)^[2][3][4] which is involved in glucuronidation. Since some drugs are disposed of by similar pathways there could be differences in hepatic clearance of them and dose-effect curves, but this is not regarded as a clinical problem.

Genetics

Autosomal recessive. The gene defect is in the promoter region, rather than the coding area (which produces the structure of the enzyme) - it is the control rather than the recipe which is the variant. Induction of liver enzymes tends to reduce the bilirubin level. This is better seen as an instance of heterogeneity in the human population than as anything like a disease.

Incidence

Quoted as 5% in various US^[5] and UK sources. Variation with ethnic group is not noted. (The mild jaundice is more noticeable in a pale skin than a dark one, therefore it will be under-recognised).

Symptoms

• Usually asymptomatic
• Some (phenotype-dependent), very rarely can have
  • Jaundice at times of
    • Intercurrent infection
    • Repeated vomiting
    • Exertion
    • Severe Stress
  • Tiredness
  • Weakness
  • Abdominal pain

Management

• Reassurance of patient
• Education of doctor who asks for a second opinion.

Contraception and Gilbert's syndrome

Since most cases go unnoticed, this is probably irrelevant. The bilirubin concentration has been seen to rise, but also to fall, with the combined oral contraceptive pill. With no particular experimental evidence the progestogen-only methods are also regarded as safe.^[6]. Telling women with Gilbert's they have "asymptomatic liver disease" is probably inaccurate and unhelpful, discussing genes and variability may take longer but is better.

Investigation

It is discovered incidentally and the LFTs which demonstrate it are sufficient investigation. Liver biopsy would be the obvious investigation but should clearly not be done because of poor risk benefit ratio.

In principle, characterising the gene responsible might be done.

See also

• Criggler-Najar syndrome (rarer, same enzyme).

Other ResourcesReferences

• Account of several similar conditions in useful depth with references
• Patient leaflet::Advanced patient leaflet

References