Molecular Methods for Rare Hemoglobinopathy Cases: First Brazilian Report of Pediatric Siblings with Hb O‐Arab and Alpha‐Thalassemia

Hemoglobinopathies are prevalent globally; diagnosis is complex in high genetic admixture populations like Brazil. We report, in two pediatric siblings, the first documented cases in Brazil of heterozygosity for hemoglobin (Hb) O-Arab with coinheritance of α-thalassemia (αα/-α4.2; -α3.7/-α4.2), resulting in microcytic and hypochromic anemia. Electrophoresis, high-performance liquid chromatography, HBB gene sequencing, and multiplex-polymerase chain reaction confirmed these complex genotypes. Although rare, Hb O-Arab significantly impacts clinical status, particularly in patients with coexisting hemoglobinopathies, such as α-thalassemia and Hb S, the latter resulting in a sickle cell disease form. This highlights the crucial role of molecular diagnostics, early screening, and genetic counseling in the accurate management and prevention of misdiagnosis in hemoglobinopathies.