Gilbert, disease or syndrome
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[MIM 143 500]
(Familial cholemia, hyperbilirubinemia type 1, Lereboullet Gilbert syndrome)
Prevalence: 3-7% of the general population. Autosomal recessive transmission of a mutation of the UGT1A1 gene (2q37) which codes for the family of UDP-glucuronosyltransferases 1A, among which the 1A1 form primarily metabolises paracetamol. As the locus of the gene consists of 9 exons, many combinations of homo- and heterozygous mutations are possible, which explains the great clinical variability of this disease.
Jaundice due to unconjugated bilirubin by partial deficiency in bilirubin-glucuronyl transferase (30% of normal) by mutation in the promoter-gene of the enzyme.
Rare cause of prolonged neonatal jaundice. Subicterus in case of infection or fasting. Benign disease.
Anesthetic implications:
depending on the number of mutated subfamilies, decrease of glucuronidation of paracetamol : there may be greater toxic risk (oxidative pathway) in case of overdose. Subicterus in the postoperative period necessitating a differential diagnosis of postoperative jaundice.
References :
- de Marais SMF, Uetrecht JP, Welles PG.
Decreased glucuronidation and increased bioactivation of acetaminophen in Gilbert's syndrome.
Gastroenterology 1992; 102: 577-86.
- Estaban A, Perez-Mateo M.
Heterogeneity of paracetamol metabolism in Gilbert’s syndrome.
Eur J Drug Metabol & Pharmacokinetics 1999; 24: 9-13.
- Nakagawa T, Mure T, Yusoff, Ono E et al.
Acetaminophen administration in a patient with Gilbert’s syndrome.
Pediatr Internat 2012; 54: 934-6.
- Nag DS, Sinha N, Samaddar DP, Mahanty PR.
General anesthesia in a patient with Gilbert’s syndrome.
J Anaesth Clin Pharmacol 2011; 27: 253-5
- Watchko JF.
Genetics and pediatric unconjugated hyperbilirubinemia.
J Pediatr 2013; 162: 1092-4.
Updated: April 2019