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

Abstract 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 α 0 -thalassemia in the father and α 0 -thalassemia (-- SEA ) with unknown α + -thalassemia in the mother. Fetal DNA analysis unlikely identified a homozygosity for α 0 -thalassemia (-- SEA /-- SEA ). Further analysis identified that the father carried a rare South African α 0 -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 α 0 -thalassemia alleles found in the population to effectively prevent a fatal condition of Hb Bart’s hydrops fetalis syndrome.