Deletion in one of the beta-globin gene clusters resulting in increased HbF and decreased HbA is most consistent with which condition?

• A. Hemolytic anemia due to G6PD deficiency
• B. Sickle cell disease
• C. Hereditary persistence of fetal hemoglobin
• D. Beta-thalassemia trait

Answer: (C)

The pattern described shows hereditary persistence of fetal hemoglobin. When a large deletion removes the beta-globin and delta-globin genes on one chromosome, the adult beta-globin production from that chromosome is lost, while the gamma-globin genes (which make HbF) remain expressed. As a result, HbF levels rise and HbA (adult hemoglobin) decreases because one beta-globin gene cluster is absent. Clinically, this condition can be mild or asymptomatic since HbF can substitute somewhat for HbA.

This differs from G6PD deficiency, which causes hemolysis but doesn’t specifically alter HbF or HbA levels. It also differs from sickle cell disease, which is due to a mutation in the beta-globin gene producing HbS rather than a deletion that shifts Hb production. Beta-thalassemia trait involves reduced beta-globin production from mutations rather than a deletion of a gene cluster, so the specific pattern of increased HbF with decreased HbA from a deletion points to hereditary persistence of fetal hemoglobin.