UGT1A1 gene
Also known as: Hyperbilirubinemia, Crigler-Najjar type I; HBLRCN1; Crigler-Najjar type II; Crigler-Najjar syndrome
Includes:
OMIM#218800 https://omim.org/entry/218800
OMIM#606785 https://omim.org/entry/606785
1. The disease
A rare hereditary disorder of bilirubin metabolism characterized by unconjugated hyperbilirubinemia due to either a complete (type 1) or partial and inducible (type 2) hepatic deficit of UDP-glucuronosyltransferase 1A1 activity. The disorder manifests with neonatal jaundice with a risk of developing bilirubin encephalopathy.
2. The symptoms
First clinical manifestations usually appear soon after birth, presenting with isolated jaundice that is more severe in CNS type 1 (CNS1) than in CNS type 2 (CNS2). In CNS1, it may evolve to bilirubin encephalopathy (kernicterus) with hypertonia, deafness, oculomotor palsy and lethargy when the treatment is delayed or inadequate. In CNS2, the risk of kernicterus is much lower but does exist. Lack of early signs or symptoms does not exclude the diagnosis.
3. Actions to take in case of early diagnosis
- Infants with a positive genetic test (having 2 pathogenic variants or 2 copies of a single pathogenic variant in UGT1A1 gene) should continue breastfeeding. Early treatment can save lives.
- The physical examination can show isolated jaundice and biological analyses detect only severe unconjugated hyperbilirubinemia with normal liver function tests.
- Abdominal imaging studies (CT scans or ultrasonograms) are normal.
- Currently, definitive diagnosis relies on genomic DNA analysis (ruling out the need for liver biopsy). In the past, definitive diagnosis was based on demonstration of the enzymatic deficiency in the liver (hepatic biopsy performed after three months of age); however, liver biopsy is no longer performed.
- CNS is a life-threatening condition that requires lifetime management and regular follow-up with a paediatric gastroenterologist physician, dietician, and a multidisciplinary approach to care.
- Treatment of CNS1 relies on phototherapy (initially at hospital and then at home) for 10-12 hours per day. Bilirubin chelators and ursodeoxycholic acid may also be prescribed in these patients.
- To date, the only effective treatment for CNS1 is liver transplantation.
- Treatment of CNS2 consists of daily phenobarbital.
- Genetic counselling is highly recommended for family planning and evaluation of at-risk family members such as siblings.
4. For more information
Orphanet