Gilbert Syndrome

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 caloric intake.

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 specific adverse effects. Patients with Gilbert Syndrome are heterogeneous in terms of acetaminophen/paracetamol metabolism and a subgroup of them may exhibit a higher sensitivity to liver damage.

Crigler-Najjar Syndrome: Familial form of inherited error of bilirubin metabolism leading to hyperbilirubinemia and severe central nervous system disorder (degeneration of the basal ganglia). Caused by an enzyme deficiency in the liver in which bilirubin cannot be converted into water-soluble bilirubin glucuronide because of a defect in glucuronyl transferase.