A 3-year-old boy from Sicily has a poor appetite and is underweight for his age and height. Physical examination shows hepatosplenomegaly. The hemoglobin concentration is 6 g/dL, and the peripheral blood smear shows severely hypochromic and microcytic RBCs. The total serum iron level is normal, and the reticulocyte count is 10%. A radiograph of the skull shows maxillofacial deformities and expanded marrow spaces. Which of the following is the most likely cause of this child’s illness?
A Imbalance in α-globin and β-globin chain production
B Increased fragility of erythrocyte membranes
C Reduced synthesis of hemoglobin F
D Relative deficiency of vitamin B12
E Sequestration of iron in reticuloendothelial cells
The correct answer and explanation is:
Correct Answer: A. Imbalance in α-globin and β-globin chain production
Explanation:
This 3-year-old child presents with hepatosplenomegaly, severe microcytic hypochromic anemia, high reticulocyte count, maxillofacial deformities, and expanded marrow spaces on skull radiographs. These findings strongly suggest β-thalassemia major, a genetic disorder caused by defective or absent β-globin chain production.
Pathophysiology:
In β-thalassemia major, mutations in the HBB gene lead to deficient β-globin chain synthesis. As a result, unpaired α-globin chains accumulate, forming toxic precipitates that cause erythrocyte membrane damage and ineffective erythropoiesis. This leads to:
- Severe hemolytic anemia, requiring frequent blood transfusions
- Extramedullary hematopoiesis, causing hepatosplenomegaly
- Marrow expansion, leading to characteristic skeletal changes (frontal bossing, maxillary overgrowth, “hair-on-end” appearance on skull radiographs)
Diagnostic Findings:
- Severe microcytic hypochromic anemia (low MCV, low MCH)
- Normal total serum iron (distinguishing it from iron deficiency anemia)
- Increased reticulocyte count (indicating ongoing erythropoiesis)
- Hemoglobin electrophoresis: Increased HbF (fetal hemoglobin) and absent or reduced HbA
Treatment:
- Regular blood transfusions to prevent severe anemia
- Iron chelation therapy to prevent iron overload from transfusions
- Bone marrow transplant (curative in some cases)
This condition is most prevalent in Mediterranean populations, including Sicilians, making β-thalassemia a likely diagnosis in this child.
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