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Inborn Metabolic Disorders Causing Hyperbilirubinemia

by Steven K. Herrine, MD

Hereditary or inborn metabolic disorders may cause unconjugated or conjugated hyperbilirubinemia.

  • Unconjugated hyperbilirubinemia: Gilbert syndrome (see Gilbert Syndrome), Crigler-Najjar syndrome (see Crigler-Najjar Syndrome), and primary shunt hyperbilirubinemia

  • Conjugated hyperbilirubinemia: Dubin-Johnson syndrome and Rotor syndrome

Primary Shunt Hyperbilirubinemia

This rare, familial, benign condition is characterized by overproduction of early-labeled bilirubin (bilirubin derived from ineffective erythropoiesis and nonhemoglobin heme rather than from normal RBC turnover).

Dubin-Johnson Syndrome and Rotor Syndrome

Dubin-Johnson syndrome and Rotor syndrome cause conjugated hyperbilirubinemia, but without cholestasis, causing no symptoms or sequelae other than jaundice. In contrast to unconjugated hyperbilirubinemia in Gilbert syndrome (which also causes no other symptoms), bilirubin may appear in the urine. Aminotransferase and alkaline phosphatase levels are usually normal. Treatment is unnecessary.

Dubin-Johnson syndrome

This rare autosomal recessive disorder involves impaired excretion of bilirubin glucuronides. It is usually diagnosed by liver biopsy; the liver is deeply pigmented as a result of an intracellular melanin-like substance but is otherwise histologically normal.


Rotor syndrome

This rare disorder is clinically similar to Dubin-Johnson syndrome, but the liver is not pigmented, and other subtle metabolic differences are present.


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