A 5-year-old boy is brought to the office by his parents who say that he "looks yellow" and has been uncharacteristically tired lately. He has had upper respiratory tract infection symptoms for the past 3 days, including cough, rhinorrhea, sneezing, and sore throat. The parents say that "a lot of kids at daycare have been sick lately." The patient has no prior medical problems. He is consistently at the 50th percentile for height and weight. He takes no medications, and his immunizations are up to date. Pallor, scleral icterus, and palpable splenomegaly are seen on examination. Laboratory results are as follows: The patient recovers spontaneously after a few weeks. Peripheral smear of the boy's blood after recovery is shown in the exhibit. Which of the following is the most likely cause of this patient's condition?

Question

A 5-year-old boy is brought to the office by his parents who say that he "looks yellow" and has been uncharacteristically tired lately.  He has had upper respiratory tract infection symptoms for the past 3 days, including cough, rhinorrhea, sneezing, and sore throat.  The parents say that "a lot of kids at daycare have been sick lately."  The patient has no prior medical problems.  He is consistently at the 50th percentile for height and weight.  He takes no medications, and his immunizations are up to date.  Pallor, scleral icterus, and palpable splenomegaly are seen on examination.  Laboratory results are as follows:  The patient recovers spontaneously after a few weeks.  Peripheral smear of the boy's blood after recovery is shown in the exhibit.  Which of the following is the most likely cause of this patient's condition?

Quizplus · Accepted Answer

11ec160b_397f_c9c3_9249_1d53a9d0e0dc_MD0001_00 This patient's peripheral smear shows spherocytes, which are approximately two-thirds of the diameter of normal RBCs, more densely hemoglobinized at the periphery, and often lack a zone of central pallor. This patient's presentation is consistent with hereditary spherocytosis (HS), an autosomal dominant hemolytic anemia due to a red blood cell (RBC) membrane defect. The mutation in HS most often affects the plasma-membrane scaffolding proteins spectrin and ankyrin. Without this scaffolding, spherocytes are less deformable than normal RBCs and are prone to sequestration and subsequent accelerated destruction in the spleen. Clinical manifestations include hemolytic anemia, jaundice (increased RBC destruction results in greater bilirubin production), and splenomegaly (spherocytes have difficulty passing through the cords of Billroth and accumulate in the spleen). Infections can trigger hemolysis and lead to an acute hemolytic crisis, as seen in this patient. Age of diagnosis varies considerably, but many patients have jaundice and fatigue in times of increased hemolysis in the setting of viral infections. (Choice A) Glucose-6-phosphate dehydrogenase (G6PD) enzyme deficiency anemia usually follows oxidative stress. Common triggers include drugs (sulfonamide or antimalarial agents), fava beans, and infections (viral hepatitis, pneumonia, or typhoid). Peripheral smears of G6PD deficiency anemia show bite cells and Heinz bodies, not spherocytes. (Choice B) An imbalance between alpha globin and beta globin chain production results in thalassemia. In this patient, the peripheral smear has no morphologic variants associated with thalassemia, such as target cells or hypochromic microcytes. (Choice C) A nuclear maturation defect due to defective DNA synthesis is the pathophysiologic mechanism of megaloblastic anemia, which is most commonly caused by vitamin B₁₂ and folic acid deficiencies. In this patient's peripheral smear, small spherocytes are primarily seen and not the enlarged oval cells and hypersegmented neutrophils of megaloblastic anemia. (Choice D) Polymerization of hemoglobin occurs in sickle cell anemia. A missense mutation in the beta globin chain leads to the production of hemoglobin S, which has the capacity to polymerize in deoxygenated states. This polymerization leads to red blood cell membrane injury and deformation to a "sickle" shape seen on peripheral smear. Educational objective: Hereditary spherocytosis results from red cell cytoskeleton abnormalities, most commonly spectrin and ankyrin. Hemolytic anemia, jaundice, and splenomegaly are classic manifestations. Spherocytes are seen on peripheral blood smear. __________ References: Disorders of red cell membrane. (http://www.ncbi.nlm.nih.gov/pubmed/18341630) Red cell membrane: past, present, and future. (http://www.ncbi.nlm.nih.gov/pubmed/18988878) Abnormalities of the erythrocyte membrane. (http://www.ncbi.nlm.nih.gov/pubmed/24237975)

A 5-Year-Old Boy Is Brought to the Office by His