A 20-year-old man of South-East Asian origin has lifelong mild anaemia with splenomegaly. Hb 9.8 g/dL, MCV 64 fL, smear shows microcytic cells, target cells, Heinz body-like inclusions on supravital staining, and occasional golf ball inclusions. HPLC reveals 5% fast-moving haemoglobin. The most likely genotype is:

• A Deletion of one alpha globin gene (silent carrier)
• B Deletion of two alpha globin genes (alpha-thalassaemia trait)
• C Deletion of three alpha globin genes (HbH disease) ✓
• D Deletion of all four alpha globin genes

Explanation

Loss of three alpha globin genes leaves excess beta chains forming tetramers of beta4, i.e., haemoglobin H, which appears as a fast-moving fraction on electrophoresis or HPLC and forms inclusion bodies precipitated in red cells, producing the golf ball appearance with brilliant cresyl blue. One and two gene deletions produce silent carriage and mild microcytosis respectively without HbH, while four gene deletions cause gamma4 (haemoglobin Bart's) hydrops fetalis, incompatible with survival.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.