• Clinical science

Inherited hyperbilirubinemia


Hyperbilirubinemia is characterized by serum bilirubin levels of ≥ 1.1 mg/dL. In contrast to acute or chronic cholestatic liver disorders, which may also lead to increased serum bilirubin levels, syndromes associated with hyperbilirubinemia lead to isolated hyperbilirubinemia and hence do not affect liver enzymes. These syndromes cause a rise in either unconjugated or conjugated bilirubin. The clinical manifestation of hyperbilirubinemia is relatively mild; transient jaundice is the primary symptom. With the exception of Crigler-Najjar syndrome type I, inherited hyperbilirubinemia syndromes do not require medical management. Patients with hyperbilirubinemia generally have a good prognosis.


Isolated hyperbilirubinemia
Types Etiology Example

Indirect bilirubin

(unconjugated bilirubin)

  • Excess release
  • Defective conjugation

Direct bilirubin

(conjugated bilirubin)

  • Defective excretion

Individuals with Crigler-Najjar or Gilbert syndrome cannot ConjuGate bilirubin.

Individuals with Rotor syndrome or Dubin-Johnson syndrome cannot get RiD of DiRect bilirubin.

Gilbert syndrome

Crigler-Najjar syndrome

Crigler-Najjar syndrome type I

Crigler-Najjar syndrome type II (Arias syndrome)

Dubin-Johnson syndrome

In Dubin-Johnson syndrome, the liver appears Dark.

Rotor syndrome

In Rotor syndrome, the liver appears Regular (no dark pigmentation).

  • 1. Manandhar SR, Gurubacharya RL, Baral MR, Manandhar DS. A case report of Gilbert Syndrome. Kathmandu Univ Med J (KUMJ). ; 1(3): pp. 187–9. pmid: 16388228.
  • 2. Thoguluva Chandrasekar V, John S. Gilbert Syndrome. StatPearls. 2020. pmid: 29262099.
  • 3. Persico M, Persico E, Bakker CT, et al. Hepatic uptake of organic anions affects the plasma bilirubin level in subjects with Gilbert's syndrome mutations in UGT1A1. Hepatology. 2001; 33(3): pp. 627–32. doi: 10.1053/jhep.2001.22499.
  • 4. Bosma PJ. Inherited disorders of bilirubin metabolism. J Hepatol. 2003; 38(1): pp. 107–17. doi: 10.1016/s0168-8278(02)00359-8.
  • 5. Govardhan Bale, Urmila S. Avanthi, N.Rao Padaki, Mithun Sharma, N.Reddy Duvvur, V.Ravi Kanth Vishnubhotla. Incidence and Risk of Gallstone Disease in Gilbert's Syndrome Patients in Indian Population. Journal of Clinical and Experimental Hepatology. 2018; 8(4): pp. 362–366. doi: 10.1016/j.jceh.2017.12.006.
  • 6. Ieiri I, Higuchi S, Sugiyama Y. Genetic polymorphisms of uptake (OATP1B1, 1B3) and efflux (MRP2, BCRP) transporters: implications for inter-individual differences in the pharmacokinetics and pharmacodynamics of statins and other clinically relevant drugs. Expert Opinion on Drug Metabolism & Toxicology . 2009; 5(7): pp. 703–729. doi: 10.1517/17425250902976854.
  • 7. Jirsa M, Knisely AS, Schinkel A, Kmoch S. Rotor Syndrome. url: https://www.ncbi.nlm.nih.gov/books/NBK114805/ Accessed November 19, 2017.
last updated 10/21/2020
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