Skip to content

Gilbert Syndrome

BASICS

  • Also known as Meulengracht disease.
  • Benign inherited syndrome with intermittent mild unconjugated hyperbilirubinemia without hemolysis or liver disease.
  • Rarely diagnosed before puberty.
  • Pregnancy can elevate bilirubin due to relative fasting from morning sickness.

EPIDEMIOLOGY

  • Presents usually in 2nd or 3rd decade but present from birth.
  • Male predominance (2–7:1).
  • Prevalence 5-10% globally; often diagnosed during or after adolescence.

ETIOLOGY AND PATHOPHYSIOLOGY

  • Caused by decreased activity of uridine diphosphoglucuronate-glucuronosyltransferase (UDPGT) enzyme → reduced conjugation of bilirubin → elevated indirect (unconjugated) bilirubin.
  • Mutation in UGT1A1 gene promoter region.
  • Inheritance likely autosomal recessive (previously thought autosomal dominant).

RISK FACTORS

  • Male sex.
  • Family history, especially first-degree relatives.

COMMONLY ASSOCIATED CONDITIONS

  • Part of spectrum with Crigler-Najjar syndromes types I and II (which have much higher bilirubin levels).
  • Increased cholelithiasis risk in some populations.
  • Neonatal breast milk jaundice may be related.

DIAGNOSIS

HISTORY

  • Mild jaundice episodes triggered by fasting, dehydration, infection, sleep deprivation, exertion, menstruation, surgery.
  • Fatigue usually due to triggers, not GS itself.
  • Certain medications (gemfibrozil, atazanavir, indinavir, tocilizumab, ribavirin) may induce jaundice episodes.

PHYSICAL EXAM

  • Usually normal.
  • Occasional mild jaundice with triggers.
  • No stigmata of chronic liver disease.

DIFFERENTIAL DIAGNOSIS

  • Hemolysis and ineffective erythropoiesis (anemias, porphyrias, lead poisoning).
  • Cirrhosis, chronic hepatitis.
  • Pancreatitis, biliary tract disease.

DIAGNOSTIC TESTS

  • Elevated indirect bilirubin <6 mg/dL (usually <3 mg/dL), normal conjugated bilirubin.
  • Normal CBC, peripheral smear, reticulocyte count, haptoglobin, LDH, LFTs, direct Coombs.
  • Up to 60% have mild subclinical hemolysis detectable only by advanced testing.
  • Bilirubin may rise with fasting, febrile illness, or some drugs.
  • Confirm diagnosis by persistent unconjugated hyperbilirubinemia with normal labs over 3-12 months.
  • Rifampin provocation test (increase in bilirubin >1.9 mg/dL after rifampin) has 100% sensitivity and specificity but rarely needed.
  • Genetic testing for UGT1A1 mutations available but not routinely required.
  • Liver biopsy rarely indicated unless other liver disease suspected.

TREATMENT

  • No specific treatment needed.
  • Avoid unnecessary testing and procedures.
  • Educate patients and families about benign nature and inheritance.

ONGOING CARE

  • No routine monitoring once diagnosed.
  • Counsel patients to inform medical providers about diagnosis.

PATIENT EDUCATION

  • Reassure that GS is benign.
  • Identify and avoid triggers when possible.
  • Seek evaluation if jaundice is severe or prolonged.

PROGNOSIS

  • Excellent; no significant morbidity or mortality.
  • GS patients can be liver donors.
  • Possible protective effect against cardiovascular disease, type 2 diabetes, certain cancers.

COMPLICATIONS

  • None known.

ALERT

  • Caution with irinotecan chemotherapy (metabolized by UGT1A1); increased toxicity risk in GS.

REFERENCES

  1. Wagner KZ, Shiels RG, Lang CA, et al. Diagnostic criteria and contributors to Gilbert's syndrome. Crit Rev Clin Lab Sci. 2018;55(2):129-139.
  2. Kwo PY, Cohen SM, Lim JK. ACG clinical guideline: evaluation of abnormal liver chemistries. Am J Gastroenterol. 2017;112(1):18-35.

CODES

  • ICD10: E80.4 Gilbert syndrome
  • ICD10: E80.6 Other disorders of bilirubin metabolism

CLINICAL PEARLS

  • Gilbert syndrome is a benign cause of mild unconjugated hyperbilirubinemia with normal liver function tests.
  • Mutation in UGT1A1 gene promoter reduces bilirubin conjugation.
  • Diagnosis is by exclusion and persistent mild indirect hyperbilirubinemia without hemolysis.
  • Avoid unnecessary investigations; provide reassurance and education.
  • Rifampin test and genetic testing are rarely required.
  • Monitor for drug interactions, especially chemotherapy agents metabolized by UGT1A1.