What is Gilbert's syndrome (a genetic disorder characterized by mild intermittent hyperbilirubinemia)?

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From the Guidelines

Gilbert's syndrome is a benign, mild genetic liver disorder characterized by impaired bilirubin processing, leading to occasional mild jaundice, and requires no treatment. This condition affects approximately 3-7% of the population and is typically harmless, with no impact on liver function or life expectancy 1. The syndrome occurs due to a mutation in the UGT1A1 gene, reducing the liver's ability to convert bilirubin into a water-soluble form for excretion. Key characteristics of Gilbert's syndrome include:

  • Elevated unconjugated bilirubin levels, which may rise during times of stress, fasting, illness, or physical exertion
  • Occasional mild jaundice (yellowing of the skin and eyes)
  • No liver damage or impact on liver function
  • Typically discovered during routine blood tests showing slightly elevated bilirubin
  • No necessary medications, dietary restrictions, or lifestyle changes, although avoiding prolonged fasting may help prevent episodes
  • Lifelong condition with normal life expectancy. According to a recent study, even fasting, such as during Ramadan, may not significantly exacerbate the condition in the long term 1.

From the Research

Definition of Gilbert's Syndrome

  • Gilbert's syndrome (GS) is characterized by the existence of chronic mild unconjugated hyperbilirubinaemia 2
  • It is a common autosomal dominant hereditary condition with incomplete penetrance and is characterized by intermittent unconjugated hyperbilirubinemia in the absence of hepatocellular disease or hemolysis 3
  • GS is the most common inherited disorder of bilirubin metabolism 4

Key Features

  • Reduced uridine diphosphate-glucuronyl transferase activity to 30% of the normal, resulting in indirect hyperbilirubinemia 3
  • Intermittent mild jaundice in adolescence is a typical form of hyperbilirubinemia 3
  • GS may potentiate severe hyperbilirubinemia and/or cholelithiasis when combined with other prevailing conditions such as breast feeding, G-6-PD deficiency, thalassemia, spherocytosis, or cystic fibrosis 3
  • GS may also reduce plasma oxidation and affect drug metabolism 3

Diagnosis

  • Diagnosis of GS is typically one of exclusion, but molecular genetic tests can be performed when there is a diagnostic problem 3
  • The most common genotype of GS is the homozygous polymorphism A(TA)7TAA in the promoter of the gene for UDP-glucuronosyltransferase 1A1 (UGT1A1) 3
  • Rifampin test can be used as a diagnostic test for GS, with a significant increase in mean unconjugated bilirubin levels in patients with GS 2, 4, 5
  • Overnight rifampin test may be useful for the diagnosis of GS if cut-off levels for serum total and unconjugated bilirubin level of more than 2.4 and 1.3 mg/dL are used 4

Management and Prognosis

  • No specific management is necessary as GS is a benign condition 3
  • GS is present in ∼5-10% of the population and is strongly associated with reduced prevalence of chronic diseases, particularly cardiovascular diseases and type 2 diabetes mellitus 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Rifampicin test in the diagnosis of Gilbert's syndrome.

International journal of clinical practice, 2001

Research

Gilbert syndrome.

European journal of pediatrics, 2012

Research

Role of overnight rifampin test in diagnosing Gilbert's syndrome.

Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology, 2005

Research

The utility of rifampin in diagnosing Gilbert's syndrome.

The American journal of gastroenterology, 2001

Research

Diagnostic criteria and contributors to Gilbert's syndrome.

Critical reviews in clinical laboratory sciences, 2018

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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