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Volume 17, Issue 2 (June-2025 2025)
Iranian Journal of Blood and Cancer 2025, 17(2): 1-12 |
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saniei E, H. Issa A, Azarkeivan A, Abolghasemi H, Karimipoor M. Clinical and Biochemical Heterogeneity in Hemoglobin H Disease: A Comprehensive Analysis of α-Globin Mutations and Transfusion Requirements. Iranian Journal of Blood and Cancer 2025; 17 (2) :1-12
URL: http://ijbc.ir/article-1-1717-en.html
URL: http://ijbc.ir/article-1-1717-en.html
Elaheh Saniei *1 
, Abdulkareem H. Issa2 , Azita Azarkeivan3 , Hassan Abolghasemi4 , Morteza Karimipoor5
, Abdulkareem H. Issa2 , Azita Azarkeivan3 , Hassan Abolghasemi4 , Morteza Karimipoor5
1- Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq. , elahetisaniei@uomustansiriyah.edu.iq
2- Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq.
3- Iranian Blood Transfusion Organization (IBTO), High Institute for Research and Education in Transfusion Medicine, Thalassemia Clinic, Tehran, Iran.
4- Department of pediatrics, Baqiyatallah University of Medical Sciences, Tehran, Iran.
5- Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
2- Department of chemistry and biochemistry, college of medicine, Mustansiriyah University, Baghdad, Iraq.
3- Iranian Blood Transfusion Organization (IBTO), High Institute for Research and Education in Transfusion Medicine, Thalassemia Clinic, Tehran, Iran.
4- Department of pediatrics, Baqiyatallah University of Medical Sciences, Tehran, Iran.
5- Department of Molecular Medicine, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran.
Abstract: (851 Views)
Background: Hemoglobin H (Hb H) disease, a subtype of α-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–phenotype correlations in Hb H disease by assessing the relationship between α-globin mutations, transfusion dependency, and a range of hematologic and biochemical markers.
Methods: 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.
Results: Significant differences in hematologic and biochemical parameters were observed across genotypes. ND/ND patients had the highest hemoglobin (10.70 ± 1.83 g/dL), MCV (66.06 ± 8.43 fL), and HbA levels (93.72 ± 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 ± 840.60 ng/mL) and CRP (3.97 ± 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).
Conclusion: 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.
Methods: 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.
Results: Significant differences in hematologic and biochemical parameters were observed across genotypes. ND/ND patients had the highest hemoglobin (10.70 ± 1.83 g/dL), MCV (66.06 ± 8.43 fL), and HbA levels (93.72 ± 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 ± 840.60 ng/mL) and CRP (3.97 ± 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).
Conclusion: 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.
: Original Article |
Subject:
Pediatric Hematology & Oncology
Received: 2025/04/11 | Accepted: 2025/05/22 | Published: 2025/06/30
Received: 2025/04/11 | Accepted: 2025/05/22 | Published: 2025/06/30
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