Non-Transfusion-Dependent Thalassemia: A Complex Mix of Genetic Entities Yet to Be Fully Discovered

摘要

The management of patients with non-transfusion-dependent thalassaemia (NTDT) has been a challenging task: in fact, within this conventional definition, clinicians have to deal with a great variety of syndromes mixed in terms of their molecular background, clinical course, and severity which share only the characteristics that are not entirely dependent on transfusions [1, 2]. In fact, NTDT phe-notypes include patients with β-thalassemia intermedia, hemoglobin E/β-thalassemia, and Hemoglobin H disease (α-thalassemia intermedia) but also those with structural variant of hemoglobin associated with "α" or "β" thalassemia in heterozygous condition which often have analogous characteristics [3]. However, among different genetic entities of NTDT, the lack of a clear genotype-phenotype relationship further complicates this complex and extensive scenario in clinical practice [4]. Thus, despite the availability of recent guideline from Thalassemia International Federation, the strength of several treatments and follow-up recommended strategies should be confirmed in selected population [5]; in fact, most of these recommendations arise from retrospective and cross sectional studies where different patients were heterogeneously treated along their life with occasional transfusions, iron chelation, and splenectomy. Furthermore, in clinical practice, most of these recommendations are difficult to transfer into the "wide-spectrum" of phenotypes particularly in the case of patients first diagnosed in adult life.