Genotype-phenotype correlation in alpha-thalassemia: predicting genetic subgroups via laboratory parameters.

Objectives: Alpha-thalassemia is caused by deletional and/or mutational genetic abnormalities. Limited information exists in Saudi Arabia about the genotype-phenotype correlation. We asked if certain changes in laboratory parameters can predict the underlying genetic subgroup. Methods: All patients diagnosed with genetically defined alpha-thalassemia at King Saud University Medical City between 2017 and 2024 were included. Data were collected retrospectively. We hypothesized that there is no difference between the mutation and deletion groups in terms of complete blood count, hemoglobin electrophoresis parameters, or ferritin. Mann-Whitney U and independent samples Results: A total of 378 patients were identified with alpha-thalassemia, of whom 276 had deletion, 64 had mutation, and 38 had both mutation and deletion. Of the 340 patients included in the final comparative analysis, the median age was 27 years, and 216 were female. Higher indirect bilirubin (12.3% versus 4%, Conclusion: Alpha-thalassemia mutations create a distinct hematologic phenotype characterized by increased red cell size variability, indirect bilirubin, and HbH compared to deletions, supporting different pathophysiological mechanisms. These could serve as simple laboratory markers to help distinguish between alpha-thalassemia subtypes, supporting the hypothesis that mutations create a more severe hemolytic phenotype than deletions.