A 24-year-old man is evaluated for episodic anemia, jaundice, and dark urine. These episodes typically occur after the use of certain drugs or following infection. Additional history reveals that he has a brother who experiences similar episodes. Peripheral blood smear reveals red blood cells with the findings shown below. Deficiency of which of the following enzymes would most likely result in a condition similar to this patient's presentation?

Question

A 24-year-old man is evaluated for episodic anemia, jaundice, and dark urine.  These episodes typically occur after the use of certain drugs or following infection.  Additional history reveals that he has a brother who experiences similar episodes.  Peripheral blood smear reveals red blood cells with the findings shown below.  Deficiency of which of the following enzymes would most likely result in a condition similar to this patient's presentation?

Quizplus · Accepted Answer

11ec160b_36e2_14f9_9249_25a36ac50efe_MD0001_00 This patient likely has glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder causing hemolytic anemia and jaundice in response to oxidant stressors (eg, sulfonamide & antimalarial drugs, infection). Heinz bodies (oxidized hemoglobin conglomerates) precipitate in red blood cells and are removed by splenic macrophages, leaving behind characteristic bite cells. G6PD is an enzyme of the pentose phosphate pathway. It generates the reducing agent NADPH, which is essential for detoxification of hydrogen peroxide produced by partial reduction of molecular oxygen in red blood cells. In the absence of NADPH, reduced glutathione (the molecule required for reduction of hydrogen peroxide to water) remains in an oxidized state, and red blood cells become susceptible to oxidative damage. Glutathione reductase catalyzes the reduction of oxidized glutathione. Its absence leads to an inability to use NADPH to reduce glutathione, resulting in a clinical scenario similar to G6PD deficiency. (Choice A) Bisphosphoglycerate mutase is an enzyme unique to red blood cells and placental cells. It catalyzes the production of 2,3-bisphosphoglycerate, a molecule that binds to hemoglobin and increases offloading of oxygen in the tissues. (Choices C and D) Deficiency of the glycolytic enzymes hexokinase and pyruvate kinase leads to hemolytic anemia due to lack of ATP generation. However, these conditions would not present with bite cells and the hemolysis is not associated with exposure to oxidant stressors. (Choice E) Transketolase, along with transaldolase, catalyzes the nonoxidative reactions of the pentose phosphate pathway, producing the ribose sugar necessary for nucleotide synthesis. The reducing equivalent NADPH is not generated in this portion of the pathway. Educational objective: Glucose 6-phosphate dehydrogenase deficiency causes hemolytic anemia and jaundice secondary to increased oxidative stress due to the lack of NADPH. Glutathione reductase deficiency has a similar clinical consequence as its absence results in an inability to utilize NADPH to reduce glutathione.

A 24-Year-Old Man Is Evaluated for Episodic Anemia, Jaundice, and Dark