A 21-year-old man comes to the office due to yellow discoloration of his eyes after a hiking trip. The patient had a similar episode 2 years ago after fasting for a couple of days. Vital signs are within normal limits. Examination shows scleral icterus; there is no hepatosplenomegaly. Laboratory findings are as follows: Which of the following is the most likely cause of this patient's jaundice?

Question

A 21-year-old man comes to the office due to yellow discoloration of his eyes after a hiking trip.  The patient had a similar episode 2 years ago after fasting for a couple of days.  Vital signs are within normal limits.  Examination shows scleral icterus; there is no hepatosplenomegaly.  Laboratory findings are as follows:  Which of the following is the most likely cause of this patient's jaundice?

Quizplus · Accepted Answer

11ec160b_394f_437d_9249_536904a02ad6_MD0001_00 This patient's isolated elevation in unconjugated bilirubin and history of intermittent scleral icterus with an otherwise normal physical examination are consistent with Gilbert syndrome, the most common inherited disorder of bilirubin glucuronidation. In contrast to hepatobiliary disease (eg, cholestasis) in which conjugated bilirubin is elevated due to reflux back into the plasma, unconjugated hyperbilirubinemia is typically caused by increased bilirubin production (eg, hemolysis) or impaired bilirubin conjugation. In general, a key component of bilirubin metabolism is the conjugation of bilirubin with glucuronic acid in the liver by UDP glucuronosyltransferase. In Gilbert syndrome, a genetic mutation results in reduced enzymatic activity of UDP glucuronosyltransferase. Patients are usually asymptomatic but have recurrent episodes of mild unconjugated hyperbilirubinemia causing scleral icterus and jaundice, usually beginning after puberty. Episodes are typically triggered when production of unconjugated bilirubin is mildly increased, such as with stress (eg, fasting, vigorous exertion, illness). (Choice B) Dubin-Johnson syndrome is a benign, hereditary cause of hyperbilirubinemia that can present with intermittent scleral icterus. However, this condition is due to defective excretion of bilirubin by hepatocytes, which results in conjugated (not unconjugated) hyperbilirubinemia. (Choice C) Hereditary spherocytosis is characterized by poor red blood cell deformability due to an erythrocyte membrane defect (eg, spectrin, ankyrin) and leads to unconjugated hyperbilirubinemia from chronic hemolysis. Anemia, an elevated reticulocyte count, and splenomegaly would be expected. (Choice D) Inflammation of the liver due to viral infection (eg, hepatitis C) may cause hyperbilirubinemia, but significant elevations in aminotransferases would be expected. (Choice E) Choledocholithiasis leading to bile duct obstruction causes an elevation of conjugated (not unconjugated) bilirubin. In addition, alkaline phosphatase and transaminases are typically elevated, and patients usually have right upper quadrant or epigastric pain, nausea, and vomiting. Educational objective: Gilbert syndrome is a benign disorder that presents with recurrent scleral icterus and jaundice, typically triggered by stress (eg, fasting, illness). Pathogenesis involves decreased activity of UDP glucuronosyltransferase (impaired bilirubin conjugation), and an isolated mild unconjugated hyperbilirubinemia is typical.

A 21-Year-Old Man Comes to the Office Due to Yellow