Question

Hemoglobin H (HbH) disease is seen in which of the following?

• A. Deletion of 3 alpha genes
• B. Deletion of all 4 alpha genes
• C. Deletion of 3 beta genes
• D. Deletion of all 4 beta genes

Hint:

HbH is beta4 tetramer from severe alpha chain shortage, one step short of hydrops fetalis.

Answer 1

The Correct Option is A

Step 1: Recall the alpha globin genetics. There are 4 alpha globin genes (two on each chromosome 16). The severity of alpha thalassemia depends on how many of these 4 genes are deleted.
Step 2: Map deletions to phenotype. One gene deleted gives a silent carrier; two genes deleted gives alpha thalassemia trait; three genes deleted gives HbH disease; all four genes deleted gives Hb Bart hydrops fetalis (incompatible with life).
Step 3: Understand why HbH forms. When 3 of 4 alpha genes are deleted, alpha chain production is markedly reduced. The excess beta chains that cannot pair with alpha chains form tetramers of beta chains (beta4), which is called Hemoglobin H.
Step 4: Apply to the question. HbH disease therefore corresponds to deletion of 3 alpha genes.
Conclusion: The correct answer is option A, deletion of 3 alpha genes.