A newborn is found to have severe hemolytic anemia requiring transfusion. Hemoglobin electrophoresis shows only HbF and HbH (β4 tetramers). Which genotype most likely accounts for this presentation?

• A Hemoglobin H disease (−−/−α) — three gene deletion alpha thal ✓
• B Heterozygous α-thalassemia (−α/αα) — alpha thal trait
• C Homozygous α-thalassemia (−−/αα) — alpha thal minor
• D Hydrops fetalis (−−/−−) — four gene deletion alpha thal

Explanation

Hemoglobin H disease results from deletion of three of the four alpha-globin genes (−−/−α). With severely reduced alpha chains, excess beta chains form unstable beta-4 tetramers called HbH, which are detectable on electrophoresis. Patients have moderate-to-severe hemolytic anemia requiring intermittent transfusions. Hydrops fetalis (−−/−−) is incompatible with postnatal life, producing mainly Hb Bart's (gamma-4 tetramers) in stillborns or hydrops. Deletion of only one (−α/αα) or two (−−/αα or −α/−α) alpha genes causes silent carrier and alpha thal minor states respectively with minimal or no anemia.

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

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Written and medically reviewed by the StethoPrep medical team.