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) and unknown α-thalassemia in the father and α-thalassemia (--) with unknown α-thalassemia in the mother. Fetal DNA analysis unlikely identified a homozygosity for α-thalassemia (--/--). Further analysis identified that the father carried a rare South African α-thalassemia in combination with α-thalassemia (--/-α), whereas the mother was a patient with Hb H-Queens Park disease (--/αα). The fetus was, in fact, a compound heterozygote for (--/--).

CONCLUSIONS

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