Castelgrande Fulvio, Viola Gemma, Calabrese Cinzia, Iozzo Mariannina, Massoud Renato, Pieri Massimo, Minieri Marilena, Adorno Gaspare, Bernardini Sergio, Terrinoni Alessandro
School of Laboratory Medicine and Pathology, University of Rome Tor Vergata, Via Cracovia, 00133 Rome, Italy.
These three authors contributed to the study equally.
J Hematol. 2024 Jun;13(3):108-115. doi: 10.14740/jh1204. Epub 2024 Jun 28.
Thalassemic diseases are characterized by a reduced (β) or absent (β) synthesis of the globin chains of hemoglobin (Hb) due to genetic mutations. β-thalassemia was more frequent in the Mediterranean area, but now it is diffused worldwide. Three possible genetic forms can be distinguished: β/β, the most severe (Cooley's disease); β/β of intermediate severity; β/β associated with β-thalassemia intermedia or minor. Recently, a clinical non-genetic classification has been proposed: transfusion-dependent thalassemia (TDT), requiring regular lifetime blood transfusions, and non-transfusion-dependent thalassemia (NTDT), requiring occasional transfusions to manage acute cases. In this report, we studied a patient whose blood count indicated a severe anemia but also showed thrombocytosis, leukocytosis, and an elevated number of nucleated red blood cells (NRBC). These altered blood parameters suggested initially a possible diagnosis of hemoglobinopathy or myeloproliferative syndrome. The molecular and genetic analyses demonstrated the presence of HbF (5.3%) and HbA2 (7.7%) and the presence of the homozygote mutation (IVS1.6T>C) in the β-globin gene. According to these data, a diagnosis of β-thalassemia intermedia form has been proposed. Nevertheless, the clinical condition, the presence of thrombocytosis, leukocytosis, an elevated number of NRBC, and the frequent blood transfusions lead to reclassification of the patient as TDT subject. Consequently, this result suggests that a unique genotype-phenotype correlation is not possible in the presence of βmutations since other concomitant pathologies can exacerbate the disease.
地中海贫血症的特征是由于基因突变导致血红蛋白（Hb）的珠蛋白链合成减少（β型）或缺失（β型）。β地中海贫血在地中海地区更为常见，但现在已遍布全球。可区分出三种可能的遗传形式：β/β，最为严重（库利氏病）；中等严重程度的β/β；与中间型或轻型β地中海贫血相关的β/β。最近，有人提出了一种临床非遗传分类：依赖输血的地中海贫血（TDT），需要终生定期输血；非依赖输血的地中海贫血（NTDT），需要偶尔输血以处理急性病例。在本报告中，我们研究了一名患者，其血细胞计数显示严重贫血，但也表现出血小板增多、白细胞增多以及有核红细胞（NRBC）数量增加。这些改变的血液参数最初提示可能诊断为血红蛋白病或骨髓增殖综合征。分子和基因分析显示存在HbF（5.3%）和HbA2（7.7%），并且在β珠蛋白基因中存在纯合子突变（IVS1.6T>C）。根据这些数据，提出了中间型β地中海贫血的诊断。然而，临床状况、血小板增多、白细胞增多、NRBC数量增加以及频繁输血导致该患者被重新分类为TDT患者。因此，这一结果表明，在存在β突变的情况下，由于其他伴随疾病会加重病情，所以不可能存在独特的基因型-表型相关性。
