Diagnostic challenges and the importance of genetic testing in α/β-thalassemia: a case report

Co-inheritance of α- and β-thalassemia presents major diagnostic challenges, particularly in infancy, when standard hematologic parameters are often misleading. Reliance on routine hemoglobin analysis alone may therefore lead to delayed or missed diagnosis.

We report a case of a 4-month-old female infant who presented with severe transfusion-dependent anemia, pallor, lethargy, and hepatosplenomegaly. Comprehensive laboratory evaluation included peripheral blood film, hemolysis workup, hemoglobin capillary electrophoresis, and molecular genetic testing using multiplex polymerase chain reaction and reverse hybridization.

Initial investigations revealed normocytic normochromic anemia with hemolytic features. Capillary electrophoresis showed normal adult hemoglobin A2 and mildly elevated fetal hemoglobin, insufficient to explain the clinical severity. Molecular analysis identified a heterozygous ‒α4.2 deletion and a heterozygous IVSI-5(G>C) mutation, confirming compound heterozygous α/β-thalassemia.

This case illustrates how age-related hemoglobin expression and the masking effect of α-thalassemia can render capillary electrophoresis nondiagnostic in infants with β-thalassemia. Genetic testing provided definitive diagnosis and underscores its critical role in diagnosing infants with unexplained or disproportionate anemia. Early molecular confirmation enables accurate diagnosis, appropriate counseling, and optimized clinical management.