Prenatal diagnostic errors in hemoglobin Bart's hydrops fetalis caused by rare genetic interactions of α-thalassemia.

Objectives: To describe rare genetic interactions of α-thalassemia alleles causing Hb H disease and Hb Bart's hydrops fetalis which could lead to diagnostic errors in a routine practice.

Methods: Hematological and molecular characterization were carried out in a Thai family with a risk of having fetus with Hb Bart's hydrops fetalis.

Results: Both parents were found to be the thalassemia intermedia patients associated with unusual forms of Hb H disease. DNA analysis of common α-thalassemia mutations in Thailand identified α⁺-thalassemia (-α^{3.7 kb del}) and unknown α⁰-thalassemia in the father and α⁰-thalassemia (--^SEA) with unknown α⁺-thalassemia in the mother. Fetal DNA analysis unlikely identified a homozygosity for α⁰-thalassemia (--^SEA/--^SEA). Further analysis identified that the father carried a rare South African α⁰-thalassemia in combination with α⁺-thalassemia (--^SA/-α), whereas the mother was a patient with Hb H-Queens Park disease (--^SEA/αα^QP). The fetus was, in fact, a compound heterozygote for (--^SA/--^SEA).

Conclusions: As shown in this study, routine screening for α-thalassemia at prenatal diagnosis in the region should include both common and rare α⁰-thalassemia alleles found in the population to effectively prevent a fatal condition of Hb Bart's hydrops fetalis syndrome.