Deletion of all four alpha-globin genes is associated with which fetal condition?

• A. Hydrops fetalis
• B. Hb Bart's
• C. HbH disease
• D. Thalassemia trait

Answer: (A)

Deleting all four alpha-globin genes stops alpha-chain production entirely. Without alpha chains, red cells cannot form normal HbA, and instead a gamma4 tetramer called Hb Bart’s appears in the fetus. Hb Bart’s binds oxygen very poorly for delivery to tissues, so the fetus develops severe anemia. The resulting injury to the fetus leads to edema and fluid accumulation—hydrops fetalis. So, the fetal condition linked with four-gene alpha-thalassemia deletions is hydrops fetalis. Hb Bart’s is the abnormal hemoglobin present in this condition, whereas HbH disease and thalassemia trait arise from fewer gene deletions and have milder or different clinical pictures.