What is the most likely diagnosis for a 20-day-old infant with non-fading jaundice (yellow discoloration of the skin) and pale stool, elevated direct bilirubin level, and total bilirubin level above normal?

Biliary Atresia

The most likely diagnosis is biliary atresia (option D), given the combination of persistent jaundice at 20 days of life, markedly elevated direct (conjugated) bilirubin of 98 μmol/L, and pale (acholic) stools—this triad is pathognomonic for extrahepatic biliary obstruction requiring urgent surgical evaluation. 1, 2

Key Diagnostic Features Supporting Biliary Atresia

Direct Hyperbilirubinemia Pattern

• The direct bilirubin of 98 μmol/L (approximately 5.7 mg/dL) represents 65% of the total bilirubin, which is diagnostic of cholestatic liver disease. 3, 2
• Any infant with conjugated hyperbilirubinemia beyond 14 days of life requires urgent evaluation for biliary atresia, as this is the most common surgically correctable cause of neonatal cholestasis. 1, 4
• The American Academy of Pediatrics mandates urgent pediatric gastroenterology referral when direct bilirubin exceeds 1.0 mg/dL at any total bilirubin level. 3

Pale (Acholic) Stools

• Pale stools indicate complete or near-complete obstruction of bile flow into the intestine, which is the hallmark clinical finding in biliary atresia. 1, 2
• While conventional teaching suggests that pigmented stools exclude biliary atresia, rare cases with complete biliary aplasia can still produce colored stools, making this an imperfect but highly specific sign. 5
• The stool color card screening strategy has improved early detection and survival in biliary atresia by alerting parents to acholic stools. 4

Age at Presentation

• At 20 days of life with persistent jaundice, this infant is in the critical window where biliary atresia typically manifests (first few weeks of life). 2
• Biliary atresia results from inflammatory destruction of intrahepatic and extrahepatic bile ducts, leading to progressive conjugated hyperbilirubinemia, cirrhosis, and hepatic failure if untreated. 1, 2

Why Other Options Are Incorrect

ABO and Rh Incompatibility (Options A & B)

• Both hemolytic diseases cause indirect (unconjugated) hyperbilirubinemia, not direct hyperbilirubinemia. 3
• These conditions present in the first 24-72 hours of life with rapidly rising bilirubin, not at 20 days. 3
• Hemolytic jaundice does not cause pale stools, as bile flow remains intact. 1

G6PD Deficiency (Option C)

• G6PD deficiency causes unconjugated hyperbilirubinemia through hemolysis, not conjugated hyperbilirubinemia. 3
• While G6PD deficiency can cause late-rising bilirubin with sudden increases, it does not produce the cholestatic pattern or acholic stools seen here. 3
• Pale stools would not occur with G6PD deficiency as bile excretion is normal. 1

Critical Management Implications

Urgency of Diagnosis

• Success of the Kasai portoenterostomy depends critically on age at surgery—ideally before 30-45 days of life and certainly before irreversible sclerosis of intrahepatic bile ducts occurs. 1, 4
• Approximately 25-35% of patients who undergo timely Kasai portoenterostomy survive more than 10 years without liver transplantation. 1
• Untreated biliary atresia is fatal within 2 years, with median survival of only 8 months. 1

Immediate Next Steps

• Urgent referral to a pediatric gastroenterologist and pediatric surgeon experienced in Kasai portoenterostomy is mandatory. 1, 4
• Hepatobiliary scintigraphy (HIDA scan) showing non-excretion of tracer into the intestine supports the diagnosis. 5, 6
• Liver biopsy typically reveals cholestasis, ductular hyperplasia, portal fibrosis, and bile plugs. 5, 6
• Exploratory laparotomy with intraoperative cholangiogram provides definitive diagnosis and allows immediate Kasai procedure if biliary atresia is confirmed. 1, 4

Common Pitfall to Avoid

• Never delay referral waiting for stools to become completely acholic—some infants with biliary atresia can have pigmented stools, and any direct hyperbilirubinemia >1.0 mg/dL warrants urgent evaluation regardless of stool color. 5, 3