A newborn presents with severe hydrops fetalis, hepatosplenomegaly, and pallor. Haemoglobin electrophoresis shows only HbH (β4 tetramers) and a trace of Hb Barts (γ4). No HbA, HbA2, or HbF is detected. Which alpha-thalassaemia genotype does this represent?
- A Alpha-thalassaemia trait (2 gene deletion: --/αα)
- B Alpha-thalassaemia major/Hb Barts hydrops fetalis (4 gene deletion: --/--) ✓
- C HbH disease (3 gene deletion: --/α-)
- D Silent carrier (1 gene deletion: -α/αα)
Correct answer: B. Alpha-thalassaemia major/Hb Barts hydrops fetalis (4 gene deletion: --/--)
Explanation
Deletion of all 4 alpha-globin genes (--/--) abolishes alpha-chain production; gamma-chains form γ4 tetramers (Hb Barts) in fetal life and beta-chains form β4 (HbH) postnatally. Without alpha-chains, no normal HbA (α2β2), HbA2 (α2δ2), or HbF (α2γ2) can be produced. Hb Barts has very high O2 affinity and does not deliver oxygen, causing severe fetal hypoxia, hydrops fetalis, and usually stillbirth. HbH disease (3-gene deletion) is less severe and is compatible with postnatal survival.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
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