A 10-year-old boy comes to the office for a first visit. His family recently came to the United States as political refugees. The patient's mother says that he has required several blood product transfusions due to anemia, but she does not have prior records available with her. On examination, the patient's temperature is 37.1 C (98.8 F). BMI is 21 kg/m². Examination is notable for conjunctival pallor and moderate splenomegaly. Laboratory results are as follows: Enzyme assays performed on circulating blood cells demonstrate low pyruvate kinase activity. Which of the following is the most likely cause of this patient's splenomegaly?

Question

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Pyruvate kinase is a glycolytic pathway enzyme that converts phosphoenolpyruvate to pyruvate, resulting in the generation of a molecule of ATP. Allosteric stimulation of pyruvate kinase (by fructose 1,6-bisphosphate) stimulates glycolysis. Mature red blood cells (RBCs), which do not contain mitochondria, rely on lactate as the main metabolite for glycolysis. Most of the ATP produced is used for transport of cations against a concentration gradient in the RBC membrane. Therefore, pyruvate kinase deficiency, which results in insufficient ATP production, disrupts this gradient, leading to water and potassium loss, defective maintenance of membrane architecture (echinocyte formation), and hemolysis. As reticuloendothelial cells in the splenic red pulp are involved in removal of damaged RBCs, their increased activity in the setting of pyruvate kinase deficiency causes them to undergo hyperplasia, resulting in splenomegaly. (Choice A) The spleen is important in fighting infectious pathogens in the body; therefore, many acute and chronic infections lead to enlargement of the spleen due to proliferation of lymphoid tissue. (Choice B) Disorders such as leukemia and lymphoma result in splenomegaly from neoplastic proliferation of lymphoid tissue within the spleen. (Choice C) Passive congestion of the spleen with blood occurs in the setting of portal hypertension, splenic vein thrombosis, or congestive heart failure. Resultant splenic sinusoid dilation can lead to splenomegaly. (Choice D) In infective endocarditis, circulating immune complexes can deposit in the kidneys and the spleen, likely contributing to splenomegaly. (Choice F) Splenomegaly in the lysosomal storage diseases Niemann-Pick disease and Gaucher disease is due to the accumulation of sphingomyelin and glucocerebrosides, respectively. Educational objective: Pyruvate kinase deficiency causes hemolytic anemia due to failure of glycolysis and resultant failure to generate sufficient ATP to maintain erythrocyte structure. In this case, splenic hyperplasia results from increased work of the splenic parenchyma, which must remove these deformed erythrocytes from the circulation.

A 10-Year-Old Boy Comes to the Office for a First