A 20-year-old man is evaluated in the clinic due to intermittent episodes of self-resolving jaundice. His symptoms are not provoked by any particular circumstances or events. The patient otherwise feels healthy and has no other symptoms. He does not use tobacco, alcohol, or illicit drugs. Complete blood count is within normal limits. Liver function studies are as follows: Liver biopsy shows abundant pigment inclusions in the lysosomes of the otherwise normal hepatocytes. Electron spin resonance spectroscopy reveals that the pigment is composed of polymers of epinephrine metabolites. Which of the following is the most likely cause of this patient's jaundice?

Question

A 20-year-old man is evaluated in the clinic due to intermittent episodes of self-resolving jaundice.  His symptoms are not provoked by any particular circumstances or events.  The patient otherwise feels healthy and has no other symptoms.  He does not use tobacco, alcohol, or illicit drugs.  Complete blood count is within normal limits.  Liver function studies are as follows:  Liver biopsy shows abundant pigment inclusions in the lysosomes of the otherwise normal hepatocytes.  Electron spin resonance spectroscopy reveals that the pigment is composed of polymers of epinephrine metabolites.  Which of the following is the most likely cause of this patient's jaundice?

Quizplus · Accepted Answer

11ec160b_3ae1_555a_9249_3b272b240f69_MD0001_00 Dubin-Johnson syndrome is a benign autosomal recessive disorder characterized by defective hepatic excretion of bilirubin glucuronides due to a mutation in the canalicular membrane transport protein. Individuals with this condition can develop episodes of jaundice, which may only become evident in the context of a trigger (eg, illness, pregnancy, oral contraceptive use). Otherwise, they are usually asymptomatic with a normal physical examination. Impaired bilirubin excretion may result in direct (conjugated) hyperbilirubinemia (eg, usually 2-5 mg/dL), but other routine laboratory tests (eg, complete blood count, liver function studies) are typically normal. Grossly, the liver appears black due to impaired excretion of epinephrine metabolites that accumulate within lysosomes. (Choice B) Impaired bilirubin conjugation is seen in conditions such as Crigler-Najjar syndrome and Gilbert syndrome and results in indirect (unconjugated) hyperbilirubinemia. (Choice C) Increased production of catecholamines is not associated with Dubin-Johnson syndrome despite the hepatocyte accumulation of epinephrine metabolites in this condition. Pheochromocytomas are catecholamine-secreting tumors of the adrenal medulla. (Choice D) Ineffective intramedullary erythropoiesis is seen in conditions such as beta-thalassemia and myelodysplasia, and can result in indirect hyperbilirubinemia. (Choice E) Low levels of serum ceruloplasmin are seen in Wilson disease, which is typically associated with liver (eg, hepatitis, cirrhosis), psychiatric (eg, depression, personality changes), and neurologic (eg, dysarthria, movement disorder) abnormalities. Educational objective: Dubin-Johnson syndrome is a benign disorder characterized by defective hepatic excretion of bilirubin glucuronides across the canalicular membrane, resulting in direct hyperbilirubinemia and jaundice. Grossly, the liver appears black due to impaired excretion of epinephrine metabolites, which histologically appear as dense pigments within lysosomes. __________ References: Hyperbilirubinemia syndromes (Gilbert-Meulengracht, Crigler-Najjar, Dubin-Johnson, and Rotor syndrome). (http://www.ncbi.nlm.nih.gov/pubmed/20955959) Inherited disorders of bilirubin transport and conjugation: new insights into molecular mechanisms and consequences. (http://www.ncbi.nlm.nih.gov/pubmed/24704527) Dubin-Johnson syndrome. (http://www.ncbi.nlm.nih.gov/pubmed/18460254)

A 20-Year-Old Man Is Evaluated in the Clinic Due to Intermittent