en Pediatric Hematology & Oncology Pediatric Hematology & Oncology پژوهشي Original Article <div style="text-align: justify;"><span style="line-height:2;"><span style="font-size:14px;"><span style="font-family:Times New Roman;"><strong>Background:</strong> Hemoglobin H (Hb H) disease, a subtype of &alpha;-thalassemia, demonstrates marked clinical heterogeneity primarily driven by underlying genotypic differences. While non-deletional mutations are typically associated with more severe phenotypes, considerable variability is observed even among patients with similar mutation classes. This study aimed to examine genotype&ndash;phenotype correlations in Hb H disease by assessing the relationship between &alpha;-globin mutations, transfusion dependency, and a range of hematologic and biochemical markers.<br> <strong>Methods: </strong>Ninety patients with confirmed Hb H disease were evaluated. Genotyping was performed via multiplex gap-PCR, Sanger sequencing, and MLPA. Patients were classified by transfusion need into transfusion-dependent (TDT), occasionally transfused (OTDT), and non-transfusion-dependent (NTDT) groups. Genotypically, patients were categorized as non-deletional homozygotes (ND/ND), compound heterozygotes (ND/D), and deletional homozygotes (D/D). Complete blood count, hemoglobin fractions, iron profile, liver enzymes, and C-reactive protein (CRP) levels were measured and analyzed.<br> <strong>Results: </strong>Significant differences in hematologic and biochemical parameters were observed across genotypes. ND/ND patients had the highest hemoglobin (10.70 &plusmn; 1.83 g/dL), MCV (66.06 &plusmn; 8.43 fL), and HbA levels (93.72 &plusmn; 5.13%), and the lowest reticulocyte counts and Hb H percentages (p < 0.01). ND/D patients exhibited lower HbA, higher Hb H, and elevated ferritin (438.66 &plusmn; 840.60 ng/mL) and CRP (3.97 &plusmn; 4.75 mg/L) levels (p < 0.05), indicating greater erythropoietic stress. Transfusion dependence was most frequent in ND/D patients, though not statistically significant (p = 0.34).<br> <strong>Conclusion: </strong>This study highlights substantial phenotypic variability within genotypic groups, challenging the binary classification of deletional versus non-deletional mutations. Integrating molecular data with functional and inflammatory biomarkers may enhance risk stratification and support individualized management of Hb H disease.</span></span></span></div> Alpha-Thalassemia, Alpha-Globins, Mutation 1 12 http://ijbc.ir/browse.php?a_code=A-10-1892-1&slc_lang=en&sid=1 Elaheh saniei elahetisaniei@uomustansiriyah.edu.iq 100319475328460012134 100319475328460012134 Yes Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq. Abdulkareem H. Issa 100319475328460012135 100319475328460012135 No Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq. Azita Azarkeivan 100319475328460012136 100319475328460012136 No Iranian Blood Transfusion Organization (IBTO), High Institute for Research and Education in Transfusion Medicine, Thalassemia Clinic, Tehran, Iran. Hassan Abolghasemi 100319475328460012137 100319475328460012137 No Department of pediatrics, Baqiyatallah University of Medical Sciences, Tehran, Iran. Morteza Karimipoor 100319475328460012138 100319475328460012138 No Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.