Pediatric Cholestatic, Metabolic, and Genetic Liver Disorders
Cholestatic disorders
Biliary atresia is the most common surgical cause of neonatal cholestasis; acholic stools, conjugated hyperbilirubinemia, and an absent or small gallbladder on ultrasound prompt urgent referral. Kasai portoenterostomy is most successful before 60 days. Alagille syndrome causes paucity of interlobular bile ducts, butterfly vertebrae, posterior embryotoxon, renal anomalies, and characteristic facies; GGT is usually high. PFIC and bile acid synthesis defects may have low or normal GGT; PFIC1 and PFIC2 are progressive and may need biliary diversion or transplant.
Metabolic and genetic disorders
Alpha-1 antitrypsin deficiency requires phenotype or genotype, not just a level. Cystic fibrosis is confirmed by sweat chloride or genetics; meconium ileus and focal biliary cirrhosis occur. Tyrosinemia type I is diagnosed by succinylacetone; nitisinone prevents HCC. Galactosemia is managed by avoiding galactose, but liver injury may persist. Wilson disease appears after age 3 with Kayser-Fleischer rings, low ceruloplasmin, high urinary copper, and Coombs-negative hemolysis; ceruloplasmin is an acute-phase reactant and unreliable. Mitochondrial and lysosomal disorders need multidisciplinary genetic evaluation.
Traps
A normal GGT does not exclude cholestasis. Breast milk jaundice is unconjugated. Do not miss choledochal cyst. Genetic testing is adjunctive; clinical and biochemical diagnosis still matters.
Worked example
A 7-week-old has jaundice, pale stools, direct bilirubin 5 mg/dL, GGT 450, and ultrasound shows a small gallbladder. Urgent hepatology and surgical evaluation for biliary atresia with intraoperative cholangiogram is indicated; do not delay for a repeat bilirubin.
Rule of thumb: conjugated jaundice plus acholic stools is biliary atresia until excluded.