Clinical and molecular characterization of novel deletions causing epsilon gamma delta beta thalassemia: Report of two cases

Abstract

Epsilon gamma delta beta (εγδβ)⁰ - thalassemia is a very rare disorder that results from large deletions in the β-globin gene cluster which abolish all regional globin chain gene expression from that allele. Since it is an exceedingly rare cause of neonatal anemia and is not detected by routine newborn screening, it is usually not suspected clinically and commonly undiagnosed or misdiagnosed. In this study, we describe two patients diagnosed in our hospital with (εγδβ)⁰-thalassemia based on the results obtained from DNA microarray analysis of their peripheral blood. The first patient of mixed European descent presented as a neonate with microcytic hemolytic anemia, hyperbilirubinemia, hypoglycemia and hypothermia, and was found to have a 2.2 Mb loss that included the entire β-globin gene cluster and the locus control region (LCR). The second patient, also of mixed European descent, presented in the neonatal period with anemia, thrombocytopenia and cutaneous extramedullary hematopoiesis, and was found to have a 59 kb loss that included the β-globin LCR, HBE1, HBG1, and HBG2 genes. Both cases highlight the importance of recognizing the clinical features of (εγδβ)⁰-thalassemia and implementing appropriate testing to clarify the diagnosis and manage the condition.

Keywords: Cutaneous hematopoiesis; DNA microarray; Epsilon gamma delta beta – thalassemia; Neonatal anemia.