A 4-year-old boy of Mediterranean descent is brought to the clinic for an evaluation of persistent fatigue and poor growth. His mother notes that he has become increasingly pale over the past several months. He was born at full term without complications, but his medical records show a progressive microcytic anemia that began around 6 months of age. On physical examination, the child is in the 5th percentile for height and weight. He has notable frontal bossing and maxillary prominence. Abdominal examination reveals significant hepatosplenomegaly. Laboratory studies show a hemoglobin of 6.2 g/dL and a mean corpuscular volume (MCV) of 58 fL.
Which of the following hemoglobin electrophoresis patterns is most likely to be found in this patient?
The correct answer is:
A) HbA: 0%, HbA2: 4%, HbF: 96%
This patient is presenting with beta-thalassemia major, also known as Cooley anemia. This condition is caused by a complete deficiency in the production of beta-globin chains (β0/β0). Symptoms typically appear after 6 months of age, when the protective effect of fetal hemoglobin (HbF, which uses gamma chains instead of beta) wears off and the body attempts to transition to adult hemoglobin (HbA, α2β2). The profound lack of HbA leads to severe hemolytic anemia and ineffective erythropoiesis. To compensate, the body undergoes massive extramedullary hematopoiesis, causing the classic physical findings of "chipmunk facies" (maxillary overgrowth) and hepatosplenomegaly. On electrophoresis, there is a total absence of HbA, with HbF making up the vast majority of the hemoglobin present.
Answer choice B: HbA: 60%, HbS: 40%, HbA2: 2%, is incorrect. This is the classic pattern for sickle cell trait. While these patients have a hemoglobinopathy, they do not have the quantitative beta-chain deficiency that leads to the severe microcytosis and skeletal changes described in the vignette.
Answer choice C: HbA: 90%, HbA2: 7%, HbF: 3%, is incorrect. This pattern, specifically the elevated HbA2 (>3.5%), is the hallmark of beta-thalassemia trait (minor). Patients with the trait are usually asymptomatic or have mild microcytic anemia, but they do not exhibit the severe growth failure or skeletal deformities seen in this child.
Answer choice E: HbA: 95%, HbH: 5%, is incorrect. The presence of HbH (β4 tetramers) indicates HbH disease, which is a form of alpha-thalassemia (3-gene deletion). While this causes microcytic anemia and splenomegaly, it is geographically more common in Southeast Asian populations and rarely presents with the extreme thalassemia major phenotype described here.
Answer choice E: HbA: 98%, HbA2: 2%, HbF: <1%, is incorrect. This represents a normal adult hemoglobin profile. It is inconsistent with a patient who has a hemoglobin of 6.2 g/dL and severe microcytosis.
Key Learning Point
Beta-thalassemia major presents in infancy with severe microcytic anemia, skeletal deformities due to expanded bone marrow, and hepatosplenomegaly. Diagnosis is confirmed by electrophoresis showing absent or severely reduced HbAand markedly elevated HbF. Treatment requires lifelong blood transfusions, which eventually necessitates iron chelation therapy to prevent secondary hemochromatosis.
