A newborn of Mediterranean descent has haemoglobin electrophoresis showing only HbF and HbH (beta4 tetramers) with no HbA. The most likely genotype is:
- A Hb Barts hydrops fetalis (--/-- : deletion of all 4 alpha-globin genes)
- B Beta-thalassaemia major (beta0/beta0) with compound heterozygosity
- C Haemoglobin Constant Spring with alpha-thalassaemia 1
- D HbH disease (alpha-thalassaemia with 3-gene deletion --/-alpha) ✓
Explanation
HbH disease results from deletion of three alpha-globin genes (--/-alpha genotype, one chromosome missing both alpha genes and the other missing one). Excess beta chains form beta4 tetramers called HbH, which is detectable on electrophoresis. Since alpha-globin is required for both HbA (alpha2beta2) and HbA2 (alpha2delta2) formation, HbA is markedly reduced; HbF (gamma2) is present in neonates and slowly replaced. Hb Barts hydrops fetalis (--/--) produces only gamma4 (Barts) and no HbH, and is typically fatal in utero or shortly after birth. Beta-thalassaemia major does not produce HbH; the excess unpaired alpha chains in that condition form inclusion bodies rather than stable tetramers.
Reference: Robbins & Cotran Pathologic Basis of Disease, 10th ed.
High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP
Written and medically reviewed by the StethoPrep medical team.