Unconjugated hyperbilirubinemia is seen in all of the following except: March 2010

Correct Answer: Dubin-Johnson syndrome
Description: Ans. C: Dubin-Johnson Syndrome Dubin-Johnson syndrome is an autosomal recessive disorder that causes an increase of conjugated bilirubin without elevation of liver enzymes (ALT, AST). This condition is associated with a defect in the ability of hepatocytes to secrete conjugated bilirubin into the bile. The conjugated hyperbilirubinemia is a result of defective endogenous and exogenous transfer of anionic conjugates from hepatocytes into the bile. Pigment deposition in lysosomes causes the liver to turn black. Other causes of conjugated/direct hyperbilirubinemia: Hepatocellular diseases: - Hepatitis: Neonatal idiopathic hepatitis Viral (Hepatitis B, C, TORCH infections) Bacterial (E. colt, urinary tract infections) - Total parenteral nutrition - Hepatic ischemia (post-ischemic damage) - Erythroblastosis fetalis (late, "Inspissated Bile Syndrome") Metabolic disorders: Alpha-1 antitrypsin deficiency Galactosemia, tyrosinemia, fructosemia Glycogen storage disorders Cystic fibrosis Biliary tree abnormalities: - Extrahepatic biliary atresia: In first 2 weeks, unconjugated bilirubin predominates; elevated conjugated bilirubin is late. - Paucity of bile ducts - Choledochal cyst - Bile plug syndrome Causes of unconjugated/indirect hyperbilirubinemia: Increased lysis of RBCs (i.e., increased hemoglobin release) - Isoimmunization (blood group incompatibility: Rh, ABO and minor blood groups) - RBC enzyme defects (e.g., G6PD deficiency, pyruvate kinase deficiency) - RBC structural abnormalities (hereditary spherocytosis, elliptocytosis) - Infection (sepsis, urinary tract infections) - Sequestered blood (e.g., cephalohematoma, bruising, intracranial hemorrhage) - Neonatal Jaundice - Polycythemia - Shoened life span of fetal RBCs Decreased hepatic uptake and conjugation of bilirubin - Immature glucuronyl transferase activity in all newborns: term infants have 1% of adult activity, preterm infants have 0.1%. - Gilbe Syndrome - Crigler Najjar Syndrome (Non-hemolytic Unconjugated Hyperbilirubinemia): inherited conjugation defect (very rare) - Breastmilk Jaundice (pregnanediol inhibits glucuronyl transferase activity) Increased enterohepatic reabsorption - Breastfeeding jaundice (due to dehydration from inadequate milk supply)
Category: Pediatrics
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