Gilbert Syndrome

Excerpt

Gilbert syndrome is a common genetic disorder affecting bilirubin metabolism in the liver. This condition, described in the early 1900s by Gilbert, Castaigne, and Lereboulette, is an autosomal recessive disorder that is a frequent cause of mild-to-moderate isolated unconjugated hyperbilirubinemia. The prevalence of Gilbert syndrome ranges from 2% to 20%, depending on an individual's ethnicity. Reduced glucuronidation of bilirubin leads to unconjugated hyperbilirubinemia and recurrent episodes of jaundice. Under normal circumstances, approximately 95% of bilirubin is unconjugated. Gilbert syndrome does not require treatment but must be distinguished from other disorders of unconjugated hyperbilirubinemia.

Various diagnoses should be considered when evaluating patients with unconjugated hyperbilirubinemia, including disorders of bilirubin uptake, conjugation, and overproduction (see Image. Metabolic Pathway for Bilirubin in the Hepatocyte). Disorders of hepatic uptake, storage, conjugation, and excretion can cause unconjugated and conjugated hyperbilirubinemia. Crigler-Najjar syndrome is characterized by marked unconjugated hyperbilirubinemia. Moreover, hemolytic reactions, ineffective erythropoiesis, and resorbing hematomas induce bilirubin overproduction and subsequent unconjugated hyperbilirubinemia. Hemolytic reactions include but are not limited to hereditary enzyme deficiencies, hemoglobinopathies, red blood cell membrane defects, infections, medications, toxins, warm autoimmune hemolytic anemia, paroxysmal cold hemoglobinuria, and cold agglutinin disease that can lead to elevated unconjugated bilirubin levels. Most patients with Gilbert syndrome are asymptomatic regarding liver disease, but they may express symptoms related to triggers. Triggers that can precipitate unconjugated hyperbilirubinemia of Gilbert syndrome include but are not limited to fasting, intercurrent illness, menstruation, and dehydration.

Other acute and chronic liver diseases typically present with unconjugated and conjugated hyperbilirubinemia. With hepatobiliary disorders, the proportion of conjugated bilirubin rises. Consequently, consideration of viral, metabolic, and autoimmune disorders of the liver is necessary when evaluating patients with hyperbilirubinemia and jaundice. Careful clinical assessment, targeted laboratory evaluation, and exclusion of other differential diagnoses associated with unconjugated hyperbilirubinemia, including other acute and chronic liver diseases, should be performed before diagnosing Gilbert syndrome. After diagnosing Gilbert syndrome, treatment is conservative with observation alone. The prognosis of patients with Gilbert syndrome is excellent.