A 12-year-old African American boy is brought to the emergency department with back pain, abdominal pain, and dark urine that began earlier this morning. The patient has never had symptoms like these before. Two days ago, he developed fever, runny nose, and cough, for which he took ibuprofen. Temperature is 37 C (98.6 F), blood pressure is 110/60 mm Hg, and pulse is 100/min. The patient appears tired and has scleral icterus. There is clear rhinorrhea. Lung examination is unremarkable. Heart sounds are normal. Abdominal examination reveals mild, diffuse tenderness with palpation, but no rebound tenderness or rigidity. There is no rash. Hemoglobin is 8.2 g/dL. Peripheral blood smear reveals bite cells and red blood cell inclusions on crystal violet staining. Which of the following is the most likely cause of this patient's condition?
This patient's upper respiratory infection (eg, fever, rhinorrhea, cough) followed a few days later by hemolytic anemia (eg, dark urine, scleral icterus, back/abdominal pain), raises strong suspicion for glucose-6-phosphate dehydrogenase (G6PD) deficiency. G6PD is an enzyme that generates NADPH, a cofactor required to make glutathione. Without glutathione, oxidative metabolites (eg, superoxide anion, hydrogen peroxide) accumulate in erythrocytes and denature/precipitate hemoglobin into Heinz bodies (dark red erythrocyte inclusions), which reduce erythrocyte flexibility and lead to red cell damage (bite cells) and lysis in the reticuloendothelial system.
Although G6PD deficiency is often clinically silent at baseline, patients can develop episodes of hemolytic anemia following exposure to oxidative triggers such as infection (activated leukocytes release reactive oxygen species), medications (eg, trimethoprim-sulfamethoxazole, nitrofurantoin), or certain foods (eg, fava beans). G6PD deficiency is X-linked and affects approximately 10% of black men in the United States; it is also commonly seen in those of Mediterranean, Middle Eastern, and Asian descent.
(Choice A) Acute intermittent porphyria is an autosomal dominant disorder due to a partial deficiency of a heme biosynthetic enzyme. Patients are largely asymptomatic but may develop episodes of abdominal pain, peripheral neuropathy, and dark red urine. Anemia and bite cells are not typically seen.
(Choice C) Hereditary spherocytosis is an autosomal dominant disorder of proteins (eg, spectrin) that provide scaffolding for red blood cells. In this disease, erythrocytes are rigid and get trapped in the fenestrations of the spleen's red pulp, leading to chronic hemolysis and splenomegaly. Peripheral blood smear shows spherocytes and increased reticulocytes.
(Choice D) Paroxysmal nocturnal hemoglobinuria is a hematopoietic stem cell disease characterized by episodes of complement-mediated hemolysis, which may be triggered by stress or infection. Most patients have fatigue, dark urine, and dyspnea; blood smear shows reticulocytosis; bite cells and Heinz bodies would not be present.
(Choice E) Sickle cell crises can be triggered by infection but are usually associated with significant pain. Furthermore, peripheral blood smear would show sickle cells.
(Choice F) Thalassemia minor is caused by mutations to 1 beta or 2 alpha globin chains. Patients are generally asymptomatic, but peripheral blood smear shows microcytic target cells. It is not associated with acute hemolytic anemia.
Educational objective:
Glucose-6-phosphate dehydrogenase deficiency is an X-linked disorder commonly seen in African American men. It is characterized by episodic hemolysis in response to oxidants, drugs, infections, or certain foods (eg, fava beans). Heinz bodies and bite cells are characteristically seen on peripheral blood smear.