Makindo Medical Notes

ℹ️ About

• 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.