A newborn is found to have hemoglobin Bart (γ4 tetramers) constituting 80% of total hemoglobin on HPLC. This hemoglobin pattern in a hydrops fetalis case indicates deletion of how many alpha-globin genes?

• A One alpha gene (--α/αα silent carrier)
• B Two alpha genes (α-thalassemia trait)
• C Three alpha genes (HbH disease — HbH 15-30%)
• D All four alpha genes (hydrops fetalis — Hb Bart >80%) ✓

Explanation

Deletion of all 4 alpha-globin genes (--/--) results in alpha-thalassemia major (hydrops fetalis) where no functional alpha chains are produced. Gamma-4 (Hb Bart) and beta-4 (HbH) tetramers form instead; both have extremely high O2 affinity and do not release oxygen to tissues. Hb Bart constitutes >80% of hemoglobin. The fetus dies in utero or at birth with severe hemolytic anemia, hydrops, and hepatosplenomegaly. HbH disease (3 deletions) shows HbH 5-30% and is clinically moderate.

Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

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