Kaplan USMLE Step 1: Weakness after antimalarial medication

If you’re preparing for the United States Medical Licensing Examination® (USMLE®) Step 1 exam, you might want to know which questions are most often missed by test-prep takers. Check out this example from Kaplan Medical, and read an expert explanation of the answer. Also check out all posts in this series.

A 31-year-old Croatian man comes to the physician because of a 3-day history of generalized weakness and nausea. He returned from a trip to Africa one day ago. During his trip, he took an antimalarial medication that was a leftover from a friend who had visited Africa a year ago. He developed weakness and nausea after taking these pills. Temperature is 37.0°C (98.6°F), pulse is 65/min, respirations are 16/min, and blood pressure is 122/72 mm Hg. Physical examination shows mild jaundice. Laboratory studies show:

• Leukocyte count: 8,000/mm³
• Hemoglobin: 10.5 g/dL
• Hematocrit: 32%
• Platelet count: 195,000/mm³
• Total bilirubin: 3.0 mg/dL
• Direct bilirubin: 0.5 mg/dL
• Alanine aminotransferase (ALT): 19 U/L
• Aspartate aminotransferase (AST): 17 U/L
• Alkaline phosphatase: 50 U/L

Peripheral blood smear shows bite cells.

Which of the following is most likely decreased as a result of this patient’s diagnosis?

A. Nicotinamide adenine dinucleotide (NADH)

B. Oxidized glutathione

C. Oxidized ubiquinone

D. Reduced glutathione

E. Reduced ubiquinone

The correct answer is D.

This patient of Mediterranean descent with a history of recent antimalarial medication use and evidence of hemolysis (anemia, increased bilirubin, and bite cells) has glucose 6-phosphate dehydrogenase (G6PD) deficiency. G6PD is required to generate NADPH, which is used by glutathione reductase to regenerate reduced glutathione. Reduced glutathione helps protect cell membranes (including red blood cell membranes) from damage caused by oxidative stress.

Choice A: This patient has a glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD deficiency results in decreased glutathione levels which, in turn, increases red blood cell (RBC) fragility. NADH is not impacted because glutathione reductase cannot use NADH to regenerate reduced glutathione.