Gilbert’s syndrome is a benign hereditary condition affecting bilirubin metabolism.
Autosomal recessive inheritance (historically described as dominant) with variable penetrance.
Affects ~2–5% of the population; often detected incidentally in young adults.

⚙️ Aetiology & Pathophysiology

Due to reduced activity (~30% of normal) of the hepatic enzyme uridine diphosphate glucuronosyltransferase (UGT1A1).
Causes impaired conjugation of bilirubin → isolated unconjugated hyperbilirubinaemia.
Unconjugated bilirubin is tightly bound to albumin → cannot cross the glomerulus → not detected in urine.
Bilirubin levels fluctuate; enzyme inducers (e.g. phenobarbitone) can reduce levels, while fasting, illness, stress, menstruation, or dehydration increase levels.

🧑‍⚕️ Clinical Features

Usually asymptomatic; discovered on routine bloods.
Mild jaundice (scleral icterus) is intermittent, often after fasting, illness, or exertion.
Normal stools & urine colour (no conjugated bilirubin present).
No hepatomegaly, no splenomegaly, no systemic symptoms.
Patients otherwise feel well — important reassurance point.

🆚 Differentials (unconjugated hyperbilirubinaemia)

Haemolysis: raised reticulocytes, LDH, low haptoglobin, possible anaemia.
Crigler–Najjar syndrome: rare, severe deficiency of UGT1A1 (type 1 fatal in neonates, type 2 milder).
Ineffective erythropoiesis: e.g. thalassaemia, megaloblastic anaemia.
Physiological neonatal jaundice: immature enzyme system in newborns.

🔬 Investigations

LFTs: normal (ALT/AST/ALP not raised).
Isolated rise in serum bilirubin, usually unconjugated, fluctuating (often <50 μmol/L).
Normal FBC (helps exclude haemolysis/anaemia).
Diagnosis is clinical + supportive; no imaging or biopsy needed if typical features.

💊 Management

No treatment required — condition is benign.
Reassure patients about harmless course and that no progression to liver disease occurs.
Advise that jaundice may appear during stress, fasting, or illness but has no long-term health impact.
Avoid unnecessary investigations or treatments once diagnosis is secure.
Phenobarbitone lowers bilirubin but is not indicated due to side effects.

📌 OSCE / Exam Tips

Buzzwords: young, healthy adult, mild intermittent jaundice, normal LFTs.
Urine normal colour = unconjugated bilirubin not excreted in urine.
Always exclude haemolysis if bilirubin higher than expected.
Reassurance is key management.

📚 References

Kumar & Clark’s Clinical Medicine, 10th edition.
BMJ Best Practice: Gilbert’s syndrome.
National Institute for Health and Care Excellence (NICE) CKS: Jaundice.

🧾 Clinical Case Examples – Gilbert’s Syndrome

Case 1 – Incidental Finding 🧑‍🎓 A 21-year-old university student attends a routine health screen for travel vaccinations. Blood tests show isolated unconjugated bilirubin of 32 μmol/L. He feels well, with no past medical history, no hepatosplenomegaly, and normal LFTs. 👉 Key Point: Asymptomatic, incidental finding of Gilbert’s. 👉 Management: Reassure, no further investigations needed.

Case 2 – Stress-Induced Jaundice 🏃 A 27-year-old man presents with yellow sclerae after running a half-marathon while fasting during Ramadan. He denies abdominal pain, pruritus, or dark urine. Exam is normal. Bloods: Bilirubin 45 μmol/L (mainly unconjugated), ALT/ALP normal. Urine dipstick: negative for bilirubin. 👉 Key Point: Gilbert’s syndrome with transient jaundice triggered by fasting and exertion. 👉 Management: Reassurance, avoid unnecessary imaging.

Case 3 – Differentials Confusion ⚖️ A 32-year-old woman reports intermittent jaundice during illness. Bloods: Bilirubin 38 μmol/L, normal Hb, reticulocytes, LDH, and haptoglobin. LFTs otherwise normal. Her GP initially suspects haemolysis but repeat tests confirm stable, isolated unconjugated hyperbilirubinaemia. 👉 Key Point: Important to differentiate from haemolysis and liver disease. 👉 Management: Diagnosis of Gilbert’s made, patient reassured about benign course.

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Gilbert's syndrome

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