Gilbert, disease or syndrome

[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. 
Pediatr 2013; 162: 1092-4.


Updated: April 2019