Gilbert Syndrome

At a glance

Gilbert Syndrome is a benign inherited disorder characterized by chronic intermittent jaundice (unconjugated hyperbilirubinemia) that does not lead to particular complications. It is not a progressive disorder (normal life expectancy; may even prolong life by preventing heart attacks).

Synonyms

Constitutional Hepatic (or Liver) Dysfunction; Familial Cholemia; Familial Nonhemolytic Jaundice; Hyperbilirubinemia I; Icterus Intermittens Juvenilis; Gilbert-LereboulletSyndrome; Gilbert-Meulengracht Syndrome; Low-Grade Chronic Hyperbilirubinemia; Meulengracht Disease; Unconjugated Benign Bilirubinemia.

History

Gilbert Syndrome was first described in 1900 by Nicolas Augustin Gilbert, a French gastroenterologist.

Incidence

Affects 2 to 13% of the population. There is a male-to-female ratio of 2 to 7:1.

Genetic inheritance

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.

Pathophysiology

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. The condition is caused by relative deficiency of glucuronyl transferase and poor uptake of unconjugated bilirubin by hepatocytes.

Diagnosis

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 caloric intake.

Clinical aspects

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.

Precautions before anesthesia

Obtain full history of familial-related disorders. Blood work should include a complete blood count (CBC) (to exclude hemolytic anemia) and assessment of liver function. Avoid unconjugated hyperbilirubinemia by close follow-up on preoperative fasting.

Anesthetic considerations

It is the commonest hereditary cause of increased bilirubin worldwide and evidence demonstrates that anesthesia can be safely administered. Implications of relative deficiency of glucuronyl transferase on metabolism and excretion of drugs are well understood. 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 ...