Pediatric hyperbilirubinemia

Direct vs Indirect

Direct bilirubin is called direct because it is directly measured through lab tests. Indirect bilirubin is derived by subtracting total bilirubin from direct bilirubin. It is indirectly calculated from direct and total bilirubin.

Conjugated (Direct)

Dubin-Johnson and Rotor have a defective DooR for the secretion of bilirubin.

Direct hyperbilirubinemia is always pathologic. It is a result of impaired excretion of bilirubin

Conjugated bilirubin is water soluble and therefore does not cause kernicterus.

Dubin-Johnson Syndrome

• D = Direct, Dark
• A mutation in the ABCC2 gene, which is responsible for a protein that helps transport bilirubin out of the liver and into the bile
  • Impaired excretion of conjugated bilirubin into bile
• black or dark-colored liver, which is a result of the pigment buildup
• Benign - No treatment indicated

Rotor Syndrome

• Autosomal recessive disorder caused by mutations in the SLCO1B1 and SLCO1B3 genes, which are responsible for producing proteins that transport bilirubin into the liver
  • Unconjugated bilirubin is able to be conjugated by UDP-glucuronosyltransferase (UGT1A1). However, there is impaired reuptake of conjugated bilirubin from the sinusoidal blood back into hepatocytes. Therefore, conjugated bilirubin leaks into the bloodstream instead of being excreted efficiently into bile.
• Liver tissue itself appears normal
• Benign - No treatment indicated

Biliary atresia

• Neonatal jaundice with a preponderance of conjugated bilirubin, as indicated by an increased direct bilirubin, is suggestive of biliary atresia.
  • Abnormal underdevelopment of the extrahepatic biliary system.
• Affected infants are able to conjugate bilirubin normally in the liver but are unable to excrete bile into the gastrointestinal lumen.
• Present with worsening jaundice caused by conjugated hyperbilirubinemia, along with pale stool, dark urine, poor weight gain, and, in untreated cases, cirrhosis, coagulopathy, and portal hypertension.
• Treatment includes surgical portoenterostomy to allow bile to be excreted or a liver transplant.

Unconjugated (Indirect)

Crigler-Najjar and Gilbert have problems with CoNjuGation of bilirubin

It is a result of impaired conjugation of bilirubin

Gilbert syndrome

• Deficiency in UDP-glucuronosyltransferase (UGT1A1).
• Benign - No treatment indicated
• Exacerbated by stressful events
• Normal hematologic workup

Crigler-Najjar Syndrome

• Type 1 (CN1)
  • Complete lack of UGT1A1
  • Liver transplantation is the only cure
• Type 2 (CN2)
  • Reduced UGT1A1 activity
  • Phototherapy can be used to help break down bilirubin, and phenobarbital may be used to increase UGT enzyme activity.