Question

A 25-year female presented with mild pallor and moderate hepatosplenomegaly. Her hemoglobin was 92 g/l and fetal hemoglobin level was 65%. She has not received any blood transfusion till date. She is most likely to be suffering from:

• A. Thalassemia major.
• B. Thalassemia intermedia.
• C. Hereditary persistent fetal hemoglobin, homozygous state.
• D. Hemoglobin D, homozygous state.

Hint:

True homozygous HPFH is clinically silent; anemia plus splenomegaly favors thalassemia intermedia.

Answer 1

The Correct Option is B

This question asks us to separate three conditions that can all show a raised fetal hemoglobin (HbF): thalassemia major, thalassemia intermedia, and homozygous hereditary persistent fetal hemoglobin (HPFH). The clues are a transfusion free course, mild pallor, a big liver and spleen, hemoglobin 9.2 g/dL, and HbF 65%.

1. Thalassemia major: this form causes severe anemia from infancy and needs lifelong regular transfusions to survive. A 25 year old who has never been transfused cannot have this diagnosis.
2. Thalassemia intermedia: patients keep a moderate hemoglobin without regular transfusions, but they still get hepatosplenomegaly from extra blood cell formation and carry raised HbF, sometimes quite high. This matches the clinical picture here closely.
3. Homozygous HPFH: gamma genes take over completely for the missing beta genes, so hemoglobin stays near normal and there is usually no anemia and no organ enlargement. Because this patient does have anemia and hepatosplenomegaly, true homozygous HPFH is not the best fit.
4. Homozygous hemoglobin D: this variant causes only mild hemolysis and does not push HbF up to 65%, so it does not explain the fetal hemoglobin finding.

Putting the findings together, a patient who is alive and well without transfusions, but who has real anemia, splenomegaly and a very high HbF, is best explained by thalassemia intermedia, a form where the body compensates partly with HbF but still cannot fully avoid anemia and organ enlargement.

Let's summarize:

• No transfusion history plus survival to adulthood rules out thalassemia major.
• Anemia and hepatosplenomegaly argue against true homozygous HPFH, which is normally silent.
• The overall picture, transfusion independent anemia with organ enlargement and high HbF, fits thalassemia intermedia.

So the most likely diagnosis is thalassemia intermedia, even though some printed answer keys list homozygous HPFH for this question.