Crigler-Najjar syndrome

Mutations in the common or in the bilirubin-specific regions of the bilirubin-uridine diphosphate glucuronosyltransferase (UGT1A1) gene, affecting its expression and/or activity, lead to different forms of unconjugated hyperbilirubinaemia (1):

• Gilbert syndrome,
• Crigler–Najjar syndrome type 1,
• Crigler–Najjar syndrome type 2

Crigler-Najjar syndrome is a rare form of congenital non-haemolytic hyperbilirubinaemia that is inherited in an autosomal recessive pattern.

Type I Crigler-Najjar syndrome

• characterized by severe symptoms due to minimal or a complete absence of enzyme activity (2)
• bile acid test in these patients showed that bile is almost completely composed by unconjugated bilirubin with only traces of mono-glucuronide bilirubin (1)
• have total serum bilirubin levels exceeding 20 mg/dL (340 μmol/L) and can increase up to 50 mg/dL (850 μmol/L) (1)
• individuals experience life-threatening and severe jaundice, requiring regular phototherapy for treatment (2)
• individuals with Type 1 Crigler-Najjir syndreom are at very high risk of developing neurological complications, including permanent damage such as kernicterus
• only curative treatment is a liver transplant

Type II Crigler-Najjar syndrome

• have a residual UGT1A1 enzymatic activity (less that 10%), which is sufficient to maintain unconjugated bilirubin levels below the risk of developing serious neurological damage (1)
• also known as Arias syndrome (1)
• have total serum bilirubin levels in the range of 3.5–20 mg/dL (60–340 μmol/L) (1)
• phototherapy may be used to lower the serum bilirubin level
• UGT1A1 enzymatic levels can be increased by treatment with phenobarbital, which stimulates UGT1A1 gene transcription (1)
• other therapeutic options include:
  • plasmapheresis
  • orlistat
  • calcium phosphate
• individuals may experience intermittent jaundice triggered by stress
• permanent neurological damage is rare
• liver transplant is rarely required

Reference:

1. Tcaciuc E, Podurean M, Tcaciuc A. Management of Crigler-Najjar syndrome. Med Pharm Rep. 2021 Aug;94(Suppl No 1):S64-S67.
2. Bhandari J, Thada PK, Shah M, et al. Crigler-Najjar Syndrome. [Updated 2024 Feb 12]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2026 Jan-.