Differences in UGT1A1 gene mutations and pathological liver changes between Chinese patients with Gilbert syndrome and Crigler-Najjar syndrome type II

Abstract

Diagnosis of Crigler-Najjar syndrome type II (CNS-II) and Gilbert syndrome (GS) based on the serum bilirubin concentration is difficult, because this parameter can fluctuate under certain conditions. The aim of this study was to explore differences in UGT1A1 gene mutations, which cause both CNS and GS, and pathological changes between CNS-II and GS.Ninety-five Chinese patients with hereditary unconjugated hyperbilirubinemia were enrolled in this study. Peripheral blood samples obtained from patients were used to evaluate bilirubin levels and for UGT1A1 gene testing. Percutaneous needle biopsy of the liver and staining of tissue samples with hematoxylin and eosin, Masson trichrome, reticulin, and Perl Prussian blue were performed for 59 patients. The Ishak scoring system was used to assess inflammatory activity and the extent of fibrosis.One hundred ninety-two UGT1A1 mutations at 6 sites were detected in the 95 patients; the most common mutation in GS was c.-3279T>G in the phenobarbital response enhancing motif of the UGT1A1 promoter, whereas the most common mutation in CNS-II was p.G71R. The frequency of heterozygous p.G71R mutations in CNS-II was significantly higher than that in GS (P = .001); however, the frequency of homozygous c.-3279T>G mutations in CNS-II was markedly lower than that in GS (P = .032). Among all patients with multiple mutations, the frequency of p.Y486D was significantly higher in CNS-II than in GS (P = .007). The frequency of compound c.-3279T>G, A(TA)7TAA, and p.G71R mutations in CNS-II was significantly higher than that in GS (P = .001). Among the 59 patients who underwent percutaneous needle biopsy, 20 had iron deposition in the liver. The frequency of hepatic iron deposition in CNS-II was significantly higher than that in GS (P = .002).The linked polymorphic mutations, A(TA)7TAA and c.-3279T>G in UGT1A1, were most strongly associated with GS, whereas mutations in the coding region, especially p.G71R and p.Y486D, were more strongly associated with CNS-II. Iron deposition was more common in liver biopsies from patients with CNS-II than in those with GS.

Gilbert syndrome with systemic lupus erythematosus presenting with persistent unconjugated hyperbilirubinemia: A case report

“…A study from a Romanian cohort demonstrated that the polymorphism with the highest frequency was the UGT1A1 7TA (UGT1A1 * 28) ( 29 ). However, a Chinese study revealed that 36.3% of patients with GS had the c.3279T>G mutation ( 30 ). And the frequency of A (TA) 7TAA was 30.6%, which was lower compared with Caucasians ( 21 ).…”

Perioperative management and anaesthetic considerations for adult patients with Gilbert’s syndrome and oral cancer: review and case report

“…To provide adequate analgesia during the intraoperative period, opioids are used. Among them, fentanyl is seen as an appropriate choice, because it is considered to be safe as it is metabolized in the liver by CYP3A4 primarily to norfentanyl (>99%) and other inactive metabolites, and its effect, after a single bolus dose, is terminated by redistribution to muscle and fat [22]. Prolonged duration of the effect of fentanyl would appear unlikely but in some cases, it may be reasonable to use a small dose.…”

Gilbert or Crigler–Najjar syndrome? Neonatal severe unconjugated hyperbilirubinemia with P364L UGT1A1 homozygosity

“…The mutation was at first identified in a heterozygous GS patient, but then it was associated both with “prolonged unconjugated hyperbilirubinemia” [ 3 ] and with CNS II (with the G71R variant or the promoter variant c.-40_-39insTA) [ 10 ]. Many studies describe patients carrying heterozygous P364L plus multiple pathological variants, resulting in high serum bilirubin levels, and in these cases the contribution of the single variant is not clear [ 5 , 10 , 11 ].…”