Clinical Scenario:
An 11-month-old boy is brought to the pediatric clinic with progressive pallor, irritability, and poor feeding for the past 4 months. He was healthy during the first 5 months of life. There is no history of bleeding or chronic diarrhea.
On examination, he is pale with mild frontal bossing. The spleen is palpable 2 cm below the left costal margin. There is no lymphadenopathy.
Laboratory investigations reveal:
- Hemoglobin: 5.8 g/dL
- MCV: 56 fL
- RBC count: 5.9 × 10¹²/L
- RDW: Normal
What is the most likely diagnosis?
A. β-Thalassemia major
B. Iron deficiency anemia
C. Hereditary spherocytosis
D. Acute lymphoblastic leukemia
E. Anemia of chronic disease
Correct answer & Explanation:
Correct Answer: A. β-Thalassemia major
Explanation
This infant most likely has β-thalassemia major, the most severe form of β-thalassemia. The disease usually becomes clinically apparent between 6 and 12 months of age, when fetal hemoglobin (HbF) declines and the infant becomes dependent on β-globin chain production for adult hemoglobin (HbA).
Several features in this child strongly support the diagnosis:
- Onset of symptoms after 6 months of age
- Severe anemia (Hb 5.8 g/dL)
- Marked microcytosis (MCV 56 fL)
- Relatively high RBC count despite severe anemia
- Normal RDW
- Splenomegaly due to extramedullary hematopoiesis and increased destruction of abnormal red blood cells
The diagnosis is confirmed by hemoglobin electrophoresis or high-performance liquid chromatography (HPLC), which typically demonstrates markedly elevated HbF with absent or markedly reduced HbA.
Why the other options are incorrect
A. β-Thalassemia major
Correct. The age of onset, severe microcytic anemia, splenomegaly, relatively high RBC count, and normal RDW are characteristic of β-thalassemia major.
B. Iron deficiency anemia
Although iron deficiency also causes microcytic anemia, it usually presents in older infants or toddlers with a history of inadequate dietary iron intake. Patients typically have a low RBC count and increased RDW, and splenomegaly is uncommon.
C. Hereditary spherocytosis
Usually presents with hemolytic anemia, jaundice, and splenomegaly. The anemia is typically normocytic or only mildly microcytic, and the peripheral smear shows spherocytes, not marked microcytosis.
D. Acute lymphoblastic leukemia
May present with pallor and splenomegaly, but children usually have additional features such as fever, bone pain, lymphadenopathy, bruising or bleeding, and abnormalities in white blood cell and platelet counts. Severe isolated microcytic anemia is unusual.
E. Anemia of chronic disease
Usually occurs in children with chronic inflammatory, infectious, or systemic illnesses. It is generally normocytic or only mildly microcytic and is not associated with marked splenomegaly or a high RBC count.
Learning Point
Features that favor β-thalassemia major over iron deficiency anemia include:
- Presentation between 6 and 12 months of age
- Severe microcytic anemia
- Relatively high RBC count
- Normal RDW
- Splenomegaly
- Peripheral smear showing target cells, marked anisopoikilocytosis, and nucleated red blood cells
- Confirmation by hemoglobin electrophoresis/HPLC showing markedly increased HbF with absent or markedly reduced HbA
This combination of clinical history, examination findings, and hematological indices is highly suggestive of β-thalassemia major and is a classic postgraduate examination scenario.
