Co-Heredity of (-α)20.5 Deletion and IVS I-1 G > A (HBB: C.92 + 1 G > A) Mutations in a Pediatric Patient: A Cause of Moderate Anemia Phenotype?

Alpha- and beta-thalassemia are inherited hemoglobinopathies caused by defects in the α- and β-globin genes, with carrier states typically showing mild or no clinical manifestations. However, co-inheritance of different globin gene defects may result in a more severe or atypical phenotype. Here, we report a unique case of co-inherited rare -α20.5 deletion, associated with α-thalassemia carrier status, and the common IVS-I-1 G > A (HBB: c0.92 + 1G > A) splice-site mutation, associated with β0-thalassemia trait. To our knowledge, this combination has not been previously reported. The proband, diagnosed at six months of age with α- and β-thalassemia carrier states, underwent MLPA for α-globin and Sanger sequencing for β-globin genes. Although both variants are pathogenic and typically cause mild microcytic erythrocytosis individually, their co-inheritance caused marked globin chain imbalance, resulting in moderate microcytic anemia and requiring red blood cell transfusion at six months. During follow-up, a gradual improvement in hematologic parameters was observed, coinciding with a physiological decline in HbF levels, strengthened erythropoietic adaptation, and maturation of iron metabolism. By 15 months of age, hemoglobin, MCV, and MCH values had normalized. This clinical trajectory suggests that the simultaneous presence of α- and β-globin gene defects may exacerbate the phenotype during the neonatal period, but the imbalance may decrease as developmental adaptation progresses.This study represents the first reported case describing the phenotype associated with the co-inheritance of the -α20.5 deletion and the IVS-I-1 G > A mutation, providing novel insight into the clinical consequences of this rare genetic combination. Therefore, larger cohort studies are warranted.