A Curse of Knowledge in Diagnosis of Thalassemia

How socioeconomic development affect the diagnosis of thalassemia? Here, we report a couple (husband and wife) from United Arab Emirates (UAE) with microcytic anemia. The parents belong to Arabian tribes with a high prevalence of a- and b-thalassemia. They wanted to have another (sixth) child and their blood counts were investigated before in vitro fertilization. The parents and five children had standard blood tests (complete blood and reticulocyte cell counts, serum ferritin, and hemoglobin analysis) followed by genetic investigations of hemoglobin-a locus 1 and 2. In addition, the parents had a genetic investigation of hemoglobin-b locus for 22 common variants. The parents were found to have no abnormality in hemoglobin-b locus. They had two pathogenic a-globin gene variants: one rare variant in the 3’ prime untranslated region of HBA2 (c.*92A>G; rs63750067) and one common deletion in HBA2 (-a3.7). There were four distinct genotypes: -a3.7 homozygote (mother), c.*92A>G heterozygote (father), double heterozygotes (four children), and -a 3.7 heterozygote (one child). The couple was cleared for the in vitro fertilization. In contrast to ‘standard’ approach, the genetic test for thalassemia is controversial. The findings in this family are discussed in the context of recent epidemiologic and genetic studies in the local population. It was concluded that the rapid development in the UAE was accompanied by acquisition of new information about thalassemia which, paradoxically, increased diagnostic uncertainties in the setting of premarital guidance.