Clinical scenario: persistent jaundice | pale stool | normal size gallbladder
A 6-week-old male infant is referred for evaluation of persistent jaundice. He was born at term and has been exclusively breastfed. He is thriving well, but his parents report intermittent pale stools over the past 10 days. Examination reveals mild hepatomegaly without splenomegaly.
Investigations show:
- Total bilirubin: 10.8 mg/dL
- Direct bilirubin: 5.2 mg/dL
- ALT: 135 U/L (elevated)
- AST: 150 U/L (elevated)
- GGT: 32 U/L (normal)
- INR: 1.4
Abdominal ultrasonography demonstrates a normal-sized gallbladder without biliary duct dilatation.
Which of the following is the most likely diagnosis?
A. Alpha-1 antitrypsin deficiency
B. Biliary atresia
C. Progressive familial intrahepatic cholestasis (PFIC)
D. Breast milk jaundice
E. Congenital hypothyroidism
Correct answer & Explanation:
Correct Answer:
C. Progressive familial intrahepatic cholestasis (PFIC)
Explanation: Progressive familial intrahepatic cholestasis (PFIC)
This infant has cholestatic jaundice (elevated direct bilirubin).
The key discriminator is the normal GGT despite significant cholestasis.
PFIC (especially PFIC types 1 and 2) classically presents with:
- Persistent neonatal cholestasis
- Normal or low GGT
- Conjugated hyperbilirubinemia
- Elevated transaminases
- Progressive liver disease
- Hepatomegaly
- Poor bile flow despite a normal extrahepatic biliary tree
The normal GGT is the clue that differentiates PFIC from biliary atresia.
Why the other options are incorrect
A. Alpha-1 antitrypsin deficiency
- Causes neonatal cholestasis, but GGT is usually elevated.
B. Biliary atresia
- Usually presents with markedly elevated GGT, persistent acholic stools, and progressive cholestasis.
- A normal GGT makes biliary atresia much less likely, although it should still be excluded clinically.
D. Breast milk jaundice
- Causes unconjugated hyperbilirubinemia.
- Direct bilirubin is normal, and stools remain pigmented.
E. Congenital hypothyroidism
- Causes prolonged unconjugated jaundice and constipation.
- It does not produce conjugated hyperbilirubinemia with elevated liver enzymes.
FCPS Pearls
- Low/normal GGT cholestasis → Think PFIC (Types 1 & 2), bile acid synthesis defects, or panhypopituitarism.
- High GGT cholestasis → Think biliary atresia, alpha-1 antitrypsin deficiency, Alagille syndrome, cystic fibrosis.
