Challenges in the Diagnosis of Beta-thalassemia Syndrome: The Importance of Molecular Diagnosis

Abstract

Patients with heterozygous β-thalassemia are generally asymptomatic. However, the intermediate phenotype is uncommon, and patients require further investigation to confirm the diagnosis. We describe a 32-year-old woman (gravida 3, para 2) with heterozygous β-thalassemia who presented with symptomatic anemia and had a history of frequent blood transfusion in each pregnancy. Physical examination was unremarkable. Laboratory results at presentation showed hypochromic microcytic anemia with reticulocytosis. Molecular study revealed intermedia phenotypes resulting from coinheritance of heterozygous β-globin chain mutation (IVS1-5) and a rare heterozygous α-globin triplication (αααanti-3.7). In this case report, we discuss the laboratory diagnostic approaches and the challenges faced in investigating this case.

Application of Targeted Next-Generation Sequencing for the Investigation of Thalassemia in a Developing Country: A Single Center Experience

“…Patients with -50 (G>A) carriers had normal hematological parameters, while the compound heterozygotes for -50 and β-thalassemia had a similar hematological presentation as that of the β-thalassemia trait [ 36 ]. By identifying that the patient had additional triplicated α-globin genes, which played a vital modifier role in exacerbating her phenotypic β-thalassemia by affecting the erythroid maturation and causing an imbalance between the α- and β-globin chains, a thalassemia intermedia phenotype was produced [ 37 , 38 ]. This was similar to the case reported by Steinberg-Shemer, O. et al, where whole exome sequencing (WES) was described as a useful tool in unraveling patients’ diagnoses, especially with atypical presentation, and additional secondary modifiers that might exacerbate the disease presentation were determined [ 39 ].…”