β-Thalassemia Major
This 1-year-old boy has β-thalassemia major (homozygous β-thalassemia), as evidenced by the severely elevated HbA2 (30%) and HbF (50%) on hemoglobin electrophoresis, combined with severe microcytic anemia, splenomegaly, and characteristic skeletal changes. 1, 2
Diagnostic Reasoning
Key Laboratory Findings That Confirm β-Thalassemia
- Hemoglobin electrophoresis is diagnostic: HbA2 at 30% (normal 2-3%) and HbF at 50% (normal 1-2%) are pathognomonic for β-thalassemia major 1, 2
- Severe microcytic anemia: Hemoglobin of 40 g/L with MCV of 70 fL indicates profound microcytic anemia 1, 2
- Elevated RBC count (5.8 × 10¹²/L) despite severe anemia is characteristic of thalassemia, where the bone marrow produces many small, poorly hemoglobinized red cells 1, 2
- Elevated reticulocyte count (2.4%) reflects the bone marrow's compensatory response to chronic hemolysis 2, 3
- Elevated RDW (14%) indicates heterogeneous red cell populations due to ineffective erythropoiesis 1, 4
Clinical Features Supporting β-Thalassemia Major
- Growth delay and short stature are characteristic of β-thalassemia major, with weight deficits occurring early and preceding linear growth failure 5
- Prominent forehead results from extramedullary hematopoiesis causing bone marrow expansion in the skull 6, 7
- Splenomegaly develops from chronic hemolysis and extramedullary hematopoiesis 6, 3, 8
- Jaundice reflects chronic hemolysis with hyperbilirubinemia 6, 3
- Pallor and lethargy result from severe anemia 6, 3
Why Other Diagnoses Are Excluded
Iron Deficiency Anemia (Option A) - Incorrect
- Hemoglobin electrophoresis would be normal in iron deficiency, not showing elevated HbA2 and HbF 1, 2
- RBC count would be low, not elevated as seen here (5.8 × 10¹²/L) 1, 2
- Ferritin would be low (<30 μg/L), and transferrin saturation would be reduced (<15-16%) 1, 2
- Iron deficiency does not cause prominent forehead or the degree of splenomegaly seen here 1
Sickle Cell Disease (Option C) - Incorrect
- Hemoglobin electrophoresis would show HbS, not elevated HbA2 and HbF in this pattern 9
- Sickle cell disease typically presents with painful vaso-occlusive crises, not primarily with this constellation of findings 9
- The MCV in sickle cell disease is typically normal or only mildly reduced, not 70 fL 9
α-Thalassemia (Option D) - Incorrect
- Hemoglobin electrophoresis would be normal or show only HbH in α-thalassemia, not markedly elevated HbA2 and HbF 1, 2
- Severe α-thalassemia (HbH disease or Bart's hydrops fetalis) presents differently, with Bart's hydrops causing intrauterine or neonatal death 1
- The specific pattern of HbA2 elevation is pathognomonic for β-thalassemia, not α-thalassemia 1, 2
Clinical Implications and Management Considerations
This child will require lifelong transfusion therapy to maintain adequate hemoglobin levels and prevent complications of chronic anemia and extramedullary hematopoiesis 7, 5
Iron chelation therapy is essential to prevent iron overload from chronic transfusions, which can cause cardiac, hepatic, and endocrine complications 7
Monitor for complications including growth failure, delayed puberty, cardiac dysfunction, hepatic disease, and endocrinopathies (particularly hypogonadism and growth hormone deficiency) 7, 5
Splenectomy may be considered if hypersplenism develops with increased transfusion requirements, though this is typically delayed until after age 5-6 years due to infection risk 3, 8
Genetic counseling for the family is indicated, as both parents are obligate carriers of β-thalassemia trait 6