Gilbert syndrome

Benign inherited (usually autosomal recessive) condition of reduced bilirubin UDP-glucuronosyltransferase (*UGT1A1*) activity; causes mild isolated unconjugated hyperbilirubinemia (intermittent jaundice).

• Very common (≈3–10% of people) benign cause of jaundice. Recognizing it prevents unnecessary workup and anxiety. Often tested as the harmless "red herring" in jaundice cases to contrast with serious liver diseases.

• Usually asymptomatic aside from episodes of mild jaundice (scleral icterus) in an otherwise healthy teen or young adult.
• Jaundice is often triggered by stress: for example, illness (like a cold/flu), fasting (skipping meals), dehydration, strenuous exercise, or menstruation.
• Labs show isolated ↑unconjugated bilirubin (typically 2–4 mg/dL) with normal liver enzymes (ALT, AST, ALP) and normal hemoglobin/reticulocyte count.

1. Suspect Gilbert if unconjugated bilirubin is mildly elevated but ALT/AST and CBC are normal (isolated indirect hyperbilirubinemia).
2. Exclude other causes: check for hemolysis (if anemia or ↑retic count, do Coombs test, etc.) and for liver injury (if ALT/AST are elevated or if direct bilirubin ↑, evaluate for hepatitis or cholestasis).
3. No invasive workup is needed in classic cases. Historically, a 48-hour fast will provoke a bilirubin rise in Gilbert, and genetic testing (*UGT1A1* mutation) can confirm the diagnosis – but this is rarely necessary.

1. No specific treatment needed – reassurance is key (it's a harmless condition).
2. Avoid extreme fasting or dehydration to reduce the frequency of jaundice episodes, but no medication or special therapy is required.

• Mnemonic: CGI – Crigler-Najjar and Gilbert cause Indirect (unconjugated) bilirubin elevation, whereas Dubin-Johnson & Rotor syndromes cause direct bilirubin elevation.
• Gilbert = mild, Crigler-Najjar = severe: Gilbert never causes kernicterus or real harm, in contrast to Crigler-Najjar type I (fatal without transplant).

• Jaundice accompanied by weight loss, abdominal pain, or general illness → not Gilbert; consider serious causes (e.g., malignancy, hepatitis).
• Abnormal liver tests (elevated ALT/AST or ALP, or high direct bilirubin) → points to true liver pathology (Gilbert's labs should otherwise be normal).

1. Noticed mild jaundice or isolated bilirubin rise → check bilirubin fraction (direct vs indirect) and other labs (LFTs, CBC).
2. If indirect bilirubin is elevated with normal AST/ALT and normal hemoglobin → Gilbert syndrome likely (benign).
3. If signs of hemolysis (anemia, ↑retic count) are present → investigate hemolytic causes (Coombs test, G6PD, etc.).
4. If direct bilirubin is elevated or liver enzymes are abnormal → evaluate for liver/biliary disease (viral hepatitis panel, ultrasound imaging, etc.).
5. Confirmed Gilbert syndrome → educate and reassure (no invasive workup or treatment needed).

• Young adult with transient scleral icterus after fasting or illness, but normal physical exam and normal liver labs → benign Gilbert syndrome (isolated unconjugated bilirubin elevation).
• Incidental finding of mildly ↑indirect bilirubin (~2–3 mg/dL) on routine labs in an otherwise healthy patient (with normal AST/ALT and no anemia) → likely Gilbert syndrome (no treatment needed).