Gilbert Syndrome

Excerpt

Gilbert syndrome is an autosomal recessive disorder of bilirubin metabolism within the liver. 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 and must be distinguished from other disorders of unconjugated hyperbilirubinemia. Alternative diseases should be considered in evaluating patients with unconjugated hyperbilirubinemia, including disorders of bilirubin uptake, conjugation, and overproduction.

Disorders of hepatic uptake, storage, conjugation, and excretion can cause unconjugated and conjugated hyperbilirubinemia. Crigler-Najjar syndrome is characterized by marked unconjugated hyperbilirubinemia. 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 both 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, exclusion of other conditions associated with unconjugated hyperbilirubinemia, and consideration of other acute and chronic liver diseases should be done before diagnosing Gilbert syndrome. After diagnosing Gilbert syndrome, treatment is conservative with observation alone. The prognosis of patients with Gilbert syndrome is excellent.