A 20-year-old man is evaluated in the emergency department for weakness, malaise, and dark urine. The patient was treated for a bacterial skin infection several days ago. Physical examination shows scleral icterus. Laboratory results reveal anemia with an elevated reticulocyte count. Abnormal erythrocytes are seen on peripheral smear. Which of the following substrate flow pathways is most likely deficient in this patient?

Question

A 20-year-old man is evaluated in the emergency department for weakness, malaise, and dark urine.  The patient was treated for a bacterial skin infection several days ago.  Physical examination shows scleral icterus.  Laboratory results reveal anemia with an elevated reticulocyte count.  Abnormal erythrocytes are seen on peripheral smear.  Which of the following substrate flow pathways is most likely deficient in this patient?

Quizplus · Accepted Answer

11ec160b_369d_b890_9249_352a5997eea3_MD0001_00 This patient is likely suffering from glucose-6-phosphate dehydrogenase (G6PD) deficiency, an X-linked recessive disorder resulting in episodic bouts of hemolysis when red blood cells experience increased oxidative stress. G6PD is the rate-limiting enzyme of the pentose phosphate pathway (PPP). This enzyme catalyzes the conversion of glucose-6-phosphate to 6-phosphogluconolactone, which is subsequently converted to 6-phosphogluconate. The PPP serves to generate both NADPH and ribose-5-phosphate, a precursor for nucleotide synthesis. Red blood cells utilize reduced NADPH to maintain a steady supply of glutathione, a molecule capable of neutralizing free radicals and therefore protecting the cells against oxidative damage. As the PPP is the only mechanism for red blood cells to generate NADPH, enzymatic defects in the pathway increase their susceptibility to oxidative damage. Increased oxidative stress can occur as a result of exposure to medications (eg, antimalarials, sulfonamides), certain foods (eg, fava beans), and infection. This patient was likely treated with a sulfonamide drug for his bacterial skin infection, which precipitated hemolytic anemia. Oxidative damage to red blood cells also causes hemoglobin to denature, forming insoluble Heinz bodies that are removed in the spleen (produces characteristic bite cells). (Choices A and B) Phosphoglucomutase interconverts glucose-6-phosphate and glucose-1-phosphate. This enzyme links glycogenolysis, glycogenesis, and glycolysis. (Choice D) This reaction is the final step in both gluconeogenesis and glycogenolysis in the liver. It is catalyzed by glucose-6-phosphatase and results in the liberation of a free glucose molecule. Enzyme deficiency results in glycogen storage disease type I. (Choice E) This reaction is the first step in glycolysis and is catalyzed by hexokinase or glucokinase. Hexokinase deficiency is a rare cause of hemolytic anemia, and glucokinase deficiency has been linked to hyperglycemic states and diabetes. (Choices F and G) Interconversion of glucose-6-phosphate and fructose-6-phosphate is catalyzed by the bidirectional enzyme phosphoglucose isomerase. Enzyme deficiency is responsible for a small percentage of hemolytic anemias. Educational objective: Glucose-6-phosphate dehydrogenase (G6PD) is the rate-limiting enzyme of the pentose phosphate pathway. G6PD deficiency is a common X-linked recessive disorder resulting in episodes of hemolytic anemia during times of increased oxidative stress (eg, use of antimalarials/sulfonamide, infections). __________ References: Glucose-6-phosphate dehydrogenase deficiency. (http://www.ncbi.nlm.nih.gov/pubmed/27040960)

A 20-Year-Old Man Is Evaluated in the Emergency Department for Weakness