IllnessGilbert syndrome, unconjugated hyperbilirubinemia

NGS + X (UGT1A1 promotor analysis)

Sanger

Gilbert syndrome is an autosomal recessively inherited, benign disorder resembling Crigler-Najjar type II (Arias syndrome). Pathogenic variants in the coding region of the UGT1A1 gene cause a largely unconjugated hyperbilirubinemia (6-20 mg/dL). Gilbert syndrome and Crigler-Najjar syndrome II are phenotypes caused by pathogenic variants with quantitatively different consequences for the UGT1A1 enzyme activity. Since the plasmatic Bilirubin level is not stable, the two phenotypes may well overlap in respective patients. Unkonjugated Hyperbilirubinemiaassociated with a homozygous A(TA)7TAA genotype, yet without pathogenic variants in the coding region of the UGT1A1 gene, should always be designated as Gilbert syndrome.

Reduced UGT1A1 activity (conjugation)

Gilbert syndrome: ≤70%

Crigler-Najjar syndrome: ≤100%

• Arias syndrome (Crigler-Najjar syndrome 2)
• Bilirubin uridinediphosphate glucuronosyltransferase deficiency type 1 (CNS1)/Type 2 (CNS2)
• Bilirubin-UGT deficiency type 1 (Crigler-Najjar syndrome 1)/Type 2 (Crigler-Najjar syndrome 2)
• Crigler-Najjar syndrome, type I (UGT1A1)
• Crigler-Najjar syndrome, type II (UGT1A1)
• Gilbert syndrome (UGT1A1)
• Hereditary unconjugated hyperbilirubinemia type 1 (Crigler-Najjar syndrome 1)/type 2 (CNS2)
• Hyperbilirubinaemia, familial transient neonatal (UGT1A1)
• UGT deficiency type 1 (Crigler-Najjar syndrome 1)/Type 2 (Crigler-Najjar syndrome 2)