A newborn is found to have hydrops fetalis and hemoglobin Barts (γ4 tetramers) on electrophoresis. What is the underlying genetic defect?

• A Deletion of both beta-globin genes (β0/β0) on chromosome 11
• B Point mutation in the beta-globin gene causing sickle hemoglobin
• C Deletion of all four alpha-globin genes (--/--) causing alpha-thalassemia major ✓
• D Deletion of two alpha genes on the same chromosome (cis deletion) in a heterozygote

Explanation

Hemoglobin Barts (γ4) forms when all four alpha-globin genes are deleted, leaving only gamma chains that form tetramers. Without alpha chains, neither fetal (HbF) nor adult (HbA) hemoglobin can be synthesized. The gamma-chain tetramers have very high oxygen affinity and cannot deliver oxygen to tissues, causing severe fetal hypoxia, hydrops fetalis, and typically intrauterine death. Deletion of two alpha genes in cis (--/αα) produces HbH disease, not Barts hydrops.

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

High-yield for: NEET PGINI-CETNExTFMGEUSMLEPLABMRCP

Written and medically reviewed by the StethoPrep medical team.