In a-thalassemia with –
**Core Concept**
Thalassemia is a genetic disorder affecting hemoglobin production, characterized by mutations in the HBB or HBA1/2 genes. This leads to reduced or absent production of the beta-globin chains of hemoglobin, resulting in anemia and other clinical manifestations.
**Why the Correct Answer is Right**
In a-thalassemia (also known as alpha-thalassemia), the mutation affects the HBA1/2 genes, which code for the alpha-globin chains of hemoglobin. This results in a decrease or absence of alpha-globin chains, leading to the production of abnormal hemoglobin (HbH or hemoglobin H) and severe anemia. The severity of the disorder depends on the number of affected genes: one gene deletion results in a mild form (alpha-thalassemia trait), two gene deletions in hemoglobin H disease, three gene deletions in beta-thalassemia intermedia, and four gene deletions in fetal death (Hb Bart's hydrops fetalis).
**Why Each Wrong Option is Incorrect**
* **Option A:** Incorrect because a-thalassemia affects the HBA1/2 genes, not the HBB gene. The HBB gene is associated with beta-thalassemia.
* **Option B:** Incorrect because a-thalassemia is characterized by a deficiency of alpha-globin chains, not beta-globin chains.
* **Option C:** Incorrect because a-thalassemia is not associated with increased production of beta-globin chains.
**Clinical Pearl / High-Yield Fact**
A key clinical feature of a-thalassemia is the presence of target cells on the peripheral smear, which can be a useful diagnostic clue.
**Correct Answer:** D.