Hereditary hyperbilirubinemias
- Topic
Some inherited defects of bilirubin handling cause jaundice; most are harmless, one can damage a baby's brain.
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 | Reduced UGT1A1 expression | Unconjugated | Normal | Benign, intermittent mild jaundice |
| Crigler-Najjar type I | Absent UGT1A1 activity | Unconjugated, very high | Normal (bile pale) | Kernicterus; transplant needed |
| Crigler-Najjar type II | Severely reduced UGT1A1 | Unconjugated | Normal | Usually good; phenobarbital lowers bilirubin |
| 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.
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.
Elsewhere in DurgiPedia
Connections
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 (MedlinePlus, US National Library of Medicine, 2026); Crigler-Najjar syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026); Dubin-Johnson syndrome: MedlinePlus Genetics (MedlinePlus, US National Library of Medicine, 2026).
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Representative model, for educational purposes only.