Review Question - QID 108445

This case is most consistent with a diagnosis of glucose-6-phosphate dehydrogenase deficiency (G6PD). G6P is the first committed enzyme in the HMP shunt and this pathway functions to generate NADPH for neutralizing oxidizing agents.

The symptom of fatigue accompanied by pallor immediately suggests that the question deals with an anemia, a suspicion confirmed by the decreased hemoglobin and hematocrit. The first step to differentiating anemias is the MCV, which is found to be normal indicating that this case is a normocytic anemia. The "tea-colored urine" and the back pain are indicative of hemoglobuinuria meaning that this case is an intrinsic hemolytic anemia. Abnormal RBCs on peripheral blood smear and triggering events can be used to further explore the differential. The peripheral blood smear shows Heinz bodies as well as bite cells, both of which are classic findings in G6PD. Of the potential triggering factors listed, a 5K might cause mild hemolysis but would not be associated with anemia. Similarly, chronic alcoholism can be associated with macrocytic anemia but acute alcohol use would not lead to this clinical syndrome. The unknown meal likely contained oxidative agents such as fava beans (high yield association) and lead to the hemolytic anemia. G6PD is an enzyme in the HMP shunt and generates NADPH for use in neutralization of oxidizing agents. Other oxidizing agents such as sulfa drugs can therefore also cause hemolysis.

Figure A shows a peripheral blood smear with RBCs containing Heinz bodies (made of denatured hemoglobin) in the upper left panel as well as bite cells (created by splenic macrophage removal of Heinz bodies) in the larger panel.

Incorrect Answers:
Answer 1: Synthesis of amino acids involves many enzymes; however, the relevant consideration for anemia is that vitamin B12 is a necessary cofactor for methionine synthase. Defective function in this pathway can lead to a megaloblastic anemia with hypersegmented neutrophils.

Answer 2: Pyruvate kinase deficiency can lead to an intravascular hemolytic anemia upon exertion due to the defect in ATP production; however, it is important to note that this disease does not present with Heinz bodies or bite cells.

Answer 3: Hemoglobin assembly requires the proper production of globin chains. Diseases involving defects in this pathway include thalassemias (genetic deletions of globin chain) as well as sickle cell (mutations causing improper globin folding patterns).

Answer 5: Porphyrin synthesis defects can lead to microcytic anemias with sideroblasts due to the inability of iron to be conjugated with porphyrins into heme. Lead poisoning also inhibits this pathway.

Bullet Summary:
Anemias should be recognized by fatigue/pallor and then be classified by MCV. G6PD can be suspected through seeing Heinz bodies/bite cells on peripheral blood smear as well as by recognizing triggering factors such as fava beans or sulfa drugs.