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# Hereditary hyperbilirubinemias

- Topic

Some inherited defects of bilirubin handling cause jaundice; most are harmless, one can damage a baby's brain.

Updated Nov 12, 2026

## Key points

- Gilbert: mild UGT1A1 reduction (promoter TA repeat); common; jaundice with fasting, stress or illness; benign.
- Crigler-Najjar type I: no UGT1A1 activity; severe neonatal jaundice and kernicterus; does not respond to phenobarbital.
- Crigler-Najjar type II: low UGT1A1 activity; milder; bilirubin falls with phenobarbital.
- Dubin-Johnson: MRP2 (ABCC2) defect; conjugated rise; black liver from pigment in lysosomes.
- Rotor: OATP1B1/1B3 defect; conjugated rise; normal-coloured liver.
- Gilbert patients metabolize some drugs (irinotecan) more slowly.

## What it is

Inherited defects of bilirubin conjugation or excretion produce isolated hyperbilirubinemia with otherwise normal liver tests. Gilbert syndrome and Crigler-Najjar syndromes affect UGT1A1 and raise unconjugated bilirubin; Dubin-Johnson and Rotor syndromes affect canalicular excretion or hepatic storage and raise conjugated bilirubin. Only Crigler-Najjar type I is dangerous, through kernicterus.

## Key facts

- All four have otherwise normal aminotransferases and alkaline phosphatase.
- Phenobarbital induces residual UGT1A1, so it helps type II but not type I.

## The four hereditary hyperbilirubinemias

| Syndrome | Defect | Bilirubin type | Liver | Course |
| --- | --- | --- | --- | --- |
| [Gilbert syndrome](https://durgical.com/en/conditions/gilbert-syndrome/) | Reduced UGT1A1 expression | Unconjugated | Normal | Benign, intermittent mild jaundice |
| [Crigler-Najjar type I](https://durgical.com/en/conditions/crigler-najjar-syndrome/) | Absent UGT1A1 activity | Unconjugated, very high | Normal (bile pale) | Kernicterus; transplant needed |
| [Crigler-Najjar type II](https://durgical.com/en/conditions/crigler-najjar-syndrome/) | Severely reduced UGT1A1 | Unconjugated | Normal | Usually good; phenobarbital lowers bilirubin |
| [Dubin-Johnson syndrome](https://durgical.com/en/conditions/dubin-johnson-syndrome/) | Absent MRP2 canalicular transporter | Conjugated | Black, dark lysosomal pigment | Benign |
| Rotor syndrome | Defective OATP1B1 and OATP1B3 uptake and storage | Conjugated | Normal colour | Benign |

## Clinical notes

- Gilbert syndrome is often found as an incidental mild unconjugated rise after fasting or a viral illness.
- Crigler-Najjar type I needs phototherapy from birth and liver transplantation.

## Memory aid

Gilbert and Crigler can't Conjugate; Dubin-Johnson is Dark and can't Drain; Rotor is the Regular-coloured cousin.

## Test yourself

Think of the answer, then tap the question to see it.

## Which hereditary hyperbilirubinemia gives a black liver?

Dubin-Johnson syndrome, from pigment retained in hepatocyte lysosomes.

## What separates Crigler-Najjar type I from type II?

Type I has no UGT1A1 activity and does not respond to phenobarbital; type II has residual activity and its bilirubin falls with phenobarbital.

## What genetic change usually underlies Gilbert syndrome?

An extra TA repeat in the UGT1A1 promoter that lowers expression of the enzyme.

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## Elsewhere in DurgiPedia

- [UGT1A1 (bilirubin UDP-glucuronosyltransferase)](https://durgical.com/en/biochemistry/enzymes/ugt1a1/)
- [Bilirubin](https://durgical.com/en/biochemistry/molecules/bilirubin/)
- [Heme breakdown and bilirubin](https://durgical.com/en/biochemistry/pathways/heme-breakdown-and-bilirubin/)

## Connections

## Related 2

- [Jaundice and cholestasis](https://durgical.com/en/general-pathology/jaundice-and-cholestasis/)
- [How a single gene causes disease: enzymes, receptors and structural proteins](https://durgical.com/en/general-pathology/how-a-single-gene-causes-disease-enzymes-receptors-and-structural-proteins/)

## Related conditions 4

- [Gilbert syndrome](https://durgical.com/en/conditions/gilbert-syndrome/)
- [Crigler-Najjar syndrome](https://durgical.com/en/conditions/crigler-najjar-syndrome/)
- [Dubin-Johnson syndrome](https://durgical.com/en/conditions/dubin-johnson-syndrome/)
- [Neonatal jaundice](https://durgical.com/en/conditions/neonatal-jaundice/)

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Educational content on the mechanisms of disease; not a diagnostic or treatment guide and no substitute for a health professional's advice. No doses are given.

Sources: [Gilbert syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/gilbert-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [Crigler-Najjar syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/crigler-najjar-syndrome/) (MedlinePlus, US National Library of Medicine, 2026); [Dubin-Johnson syndrome: MedlinePlus Genetics](https://medlineplus.gov/genetics/condition/dubin-johnson-syndrome/) (MedlinePlus, US National Library of Medicine, 2026).

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Representative model, for educational purposes only.

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Source: https://durgical.com/en/general-pathology/hereditary-hyperbilirubinemias/
License: CC BY 4.0 (https://creativecommons.org/licenses/by/4.0/). Cite as: DurgiPedia (durgical.com), https://durgical.com/en/general-pathology/hereditary-hyperbilirubinemias/