Benign inherited disorder characterized by chronic intermittent
jaundice (unconjugated hyperbilirubinemia) that does not lead to particular
complications and is not a progressive disorder (normal life expectancy; may
even prolong life by preventing heart attacks).
Constitutional Hepatic (or Liver) Dysfunction; Familial
Cholemia; Familial Nonhemolytic Jaundice; Hyperbilirubinemia I; Icterus
Intermittens Juvenilis; Gilbert-Lereboullet Syndrome; Gilbert-Meulengracht
Syndrome; Low-Grade Chronic Hyperbilirubinemia; Meulengracht Disease;
Unconjugated Benign Bilirubinemia.
Gilbert syndrome was first described in 1900 by Nicolas Augustin
Gilbert, a French gastroenterologist.
Affects 5 to 7% of the population; male-to-female
ratio is 2-7:1.
Transmission is autosomal
recessive. Mutation was identified as affecting the
promoter gene of the enzyme UDP-glucuronosyltransferase, whereas the gene
coding for the protein itself is normal. Prevalence of the mutation is 40%, but only 16% are
homozygous. Most homozygous patients have normal levels of bilirubin.
Reduced hepatic UDP-glucuronosyltransferase
(30%) activity toward bilirubin is observed in all cases. Some patients
also have defective hepatic uptake of bilirubin and other organic anions
from serum, resulting in a chronic, nonhemolytic, intermittent, unconjugated hyperbilirubinemia.
Unconjugated hyperbilirubinemia without overt
hemolysis is suspicious for the diagnosis. Serum transaminases,
phosphatases, bile salt concentration, hepatic function, and liver biopsy
are normal. Elevation of unconjugated bilirubinemia often occurs after reduced
Gilbert syndrome appears often by 10 to 12
years of age. The patient is frequently asymptomatic or has intermittent
nonhemolytic jaundice. Fatigue and abdominal discomfort are frequent
complaints that can lead to multiple diagnostic investigations and
even exploratory laparotomy. The syndrome can be associated with perioperative
jaundice in children with malnutrition and in those who received halothane
or morphine. Clinical signs are increased by fasting or infections and
decreased by phenobarbital treatment.
Obtain full history of
familial-related disorders. Blood work should include a CBC (to exclude hemolytic
anemia) and assessment of liver function. Avoid unconjugated hyperbilirubinemia
by close followup on preoperative fasting.
Regional anesthesia can be used.
Phenobarbital induces hepatic microsomal enzyme activation and reduces
bilirubin levels; however, the anesthesiologist should be aware of the
implications of enzyme induction with regard to anesthetic drugs in patients
receiving phenobarbital therapy. The halogenated agents halothane and
enflurane should be avoided because they both decrease hepatic blood flow;
isoflurane and sevoflurane appear to be acceptable agents. Concerning muscle
relaxants, drugs eliminated by the Hoffmann elimination pathway (atracurium,
cis-atracurium) or by esterases (succinylcholine, mivacurium) should be preferred.
Narcotics are metabolized in the liver, and prolonged effects of morphine
have been reported in patients with the disorder.
Inhalational anesthetics of choice are
desflurane, sevoflurane or isoflurane. Muscle relaxants such as cis-atracurium,
mivacurium or succinylcholine should be preferred. Propofol and thiopental are equally
suited for induction of anesthesia. Despite the enzyme defect, opioids can be safely used
in regular doses, although prolonged effects have been described. Remifentanil can be
used without any ...