Prenatal Diagnosis of Thalassemia

Abstract

Thalassemia is a group of inherited blood disorders that affect the production of hemoglobin. The main components of hemoglobin consist of heme and globin (α-globin and β-globin). Thalassemia occurs when there is a mutation in the genes responsible for producing these globin chains, leading to an abnormal or insufficient production of one or both types of globin. Depending on the affected globin genes, α- and β-thalassemias can be identified. Depending on the genotype, the clinical presentation of the patient can vary from asymptomatic to severe and also lethal courses. The main and also leading symptom is microcytic hypochromic anemia. Without a treatment, increased erythropoiesis can induce extramedullary hematopoiesis, hepatosplenomegaly and growth disturbances.

In the context of α-thalassemias distinctions are made among the minor and minima form (expressed by few symptoms), HbH disease (manifesting mild to moderate symptoms) and Hb Barts hydrops fetalis syndrome (showing severe symptoms and also often resulting in perinatal death). The choice of treatment depends on the specific clinical presentation and closely mirrors the approach taken for β-thalassemias.

In the case of β-thalassemias, a differentiation is made between the minor form (also with few symptoms), and the homozygous major form. Without a treatment the latter leads to severe outcomes in childhood. The symptomatic therapy involves transfusions and efforts are made to mitigate the life-limiting complications of secondary iron overload by administering iron chelators (e.g. Deferoxamine). Causal therapy is possible through a stem cell transplant, or experimentally through gene therapy.