A newborn of Southeast Asian parents presents with hydrops fetalis, severe anemia (Hb 3 g/dL), and Hb Barts on HPLC. Both parents have alpha-thalassemia trait. What is the genotype of the affected neonate?

• A --/αα (heterozygous alpha-thalassemia 1 trait)
• B --/-α (HbH disease, three alpha-gene deletions)
• C --/-- (homozygous alpha-thalassemia 1, deletion of all four alpha-globin genes) ✓
• D -α/-α (heterozygous alpha-thalassemia 2 trait)

Explanation

Hydrops fetalis with Hb Barts (γ4 tetramers) results from complete absence of alpha-globin chain production due to deletion of all four alpha-globin genes (--/-- genotype). Hb Barts has extremely high oxygen affinity (no Bohr effect), causing fatal tissue hypoxia in utero. Each parent must carry a cis double-deletion (--/αα, Southeast Asian type) to produce this offspring. HbH disease has three gene deletions (--/-α) causing a less severe phenotype.

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

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