Unconjugated Hyperbilirubinemia Differential Diagnoses

Updated: Sep 29, 2020
  • Author: Hisham Nazer, MBBCh, FRCP, DTM&H; Chief Editor: BS Anand, MD  more...
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Diagnostic Considerations

The American Academy of Pediatrics established guidelines for the diagnosis and treatment of hyperbilirubinemia in newborns in 2004. [65] These are available through the American Academy of Pediatrics.

Ineffective erythropoiesis (ELB production)

A marked increase in early-labeled bilirubin (ELB) formation has been documented in diseases associated with ineffective erythropoiesis, including the following:

  • Iron deficiency anemia

  • Pernicious anemia

  • Thalassemia

  • Erythropoietic porphyria

  • Lead poisoning

Although no specific test exists for physiologic jaundice, other causes of jaundice should be considered in infants with one or more of the following:

  • Jaundice occurring within 24 hours of birth

  • Serum concentrations of unconjugated bilirubin of 11-12 mg/dL in infants who are formula-fed or 14-15 mg/dL in infants who are breastfed

  • Increased levels of conjugated bilirubin (>2 mg/dL)

  • Jaundice persisting for more than 2 weeks

Gilbert syndrome

Gilbert syndrome has a broad differential diagnosis because numerous causes of unconjugated hyperbilirubinemia must be considered. In particular, the possibility of biliary disease must be taken into account.

Other conditions

Other conditions to be considered include the following:

  • Physiologic neonatal jaundice

  • Hemolysis

  • Hematoma

  • Acute and chronic liver disease

  • Primary hyperbilirubinemia from ineffective erythropoiesis

  • Infections

  • Cardiac disease - Eg, congestive heart failure or prosthetic heart valves

  • Rhabdomyolysis

  • High-altitude living

  • Medications - Eg, probenecid, rifampicin, or other antibiotics

  • Thyrotoxicosis

Additional considerations in the diagnosis of impaired bilirubin conjugation include the following:

  • Dyserythropoiesis

  • Portosystemic shunts

  • Neonates

  • Hyperthyroidism

  • Ethinyl estradiol

Differential Diagnoses