Thalassemia Reports

11 pages, 5814 KB

Open AccessArticle

Molecular Characterization of HBB Gene Variations in Beta-Thalassemia Patients from Khyber Pakhtunkhwa, Pakistan

by Shahzad Ahmad, Laiba Khan, Muhammad Mustafa, Yousaf Khan, Syed Farooq Shah, Fuzail Ahmad, Taimoor Khan, Muhammad Asif Zeb, Qaiser Zaman and Musharraf Jelani

Thalass. Rep. 2026, 16(3), 14; https://doi.org/10.3390/thalassrep16030014 - 10 Jul 2026

Abstract

Background: Beta-thalassemia is a hereditary hematological illness in which beta-globin chain synthesis is missing or decreased, resulting in inefficient erythropoiesis, persistent hemolysis, and anemia. It is most frequently observed in populations with a high rate of consanguineous marriages; affordability becomes a limiting factor [...] Read more.

Background: Beta-thalassemia is a hereditary hematological illness in which beta-globin chain synthesis is missing or decreased, resulting in inefficient erythropoiesis, persistent hemolysis, and anemia. It is most frequently observed in populations with a high rate of consanguineous marriages; affordability becomes a limiting factor for families with low income. Methods: In this study, we optimized Sanger sequencing of the whole HBB gene covering all three coding exons, two introns, and 5′ and 3′ UTRs. Eleven families were enrolled from Fatimid Foundation Peshawar, Khyber Pakhtunkhwa, Pakistan, with a total of 16 transfusion-dependent patients. An index patient in each family was Sanger sequenced for the HBB gene (n = 11). The variants were classified as per ACMG 2015 guidelines. Results: Sequencing analysis revealed five homozygous pathogenic variations, including three frameshifts: c.27_28dupG (p.Ser10Valfs*14), c.17_18delCT (p.Pro6Argfs17), c.126_129delCTTT (p.Phe42Leufs*19), and two splice-sites (c.92+1G>A, and c.92+5G>C) in nine families. However, two families remained unresolved. The mutation, c.27_28dupG (p.Ser10Valfs*14), was observed in several pedigrees, indicating a probable founder effect or high allele frequency within the affected population. Conclusions: The majority of detected variations in this study were classified as disease-causing, which reside in the first two coding exons and intron-1 of the HBB gene, highlighting its functional importance in the Khyber Pakhtunkhwa population. We recommend performing Sanger sequencing of exon-1-intron-1-exon-2 of the HBB gene with the optimized primers of this study. Full article

(This article belongs to the Special Issue Genetic Approach in Diagnosis and Following Up of Patients With Thalassemia)

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27 pages, 792 KB

Open AccessReview

β-Thalassemia in Vietnam: Epidemiology, Molecular Characteristics, Diagnosis, Treatment, and Prevention Strategies

by Hong-Quan Duong, Thi-Khanh Tran, Thi-Hue Nguyen and Minh-Cong Hoang

Thalass. Rep. 2026, 16(3), 13; https://doi.org/10.3390/thalassrep16030013 - 2 Jul 2026

Abstract

β-thalassemia is one of the most prevalent inherited hemoglobin disorders worldwide and represents a major public health challenge in Southeast Asia, particularly in Vietnam. The disorder is caused by pathogenic variants in the β-globin (HBB) gene, resulting in reduced or absent [...] Read more.

β-thalassemia is one of the most prevalent inherited hemoglobin disorders worldwide and represents a major public health challenge in Southeast Asia, particularly in Vietnam. The disorder is caused by pathogenic variants in the β-globin (HBB) gene, resulting in reduced or absent β-globin synthesis, ineffective erythropoiesis, chronic hemolytic anemia, and progressive multi-organ complications. Vietnam exhibits a high burden of thalassemia and related hemoglobinopathies, with approximately 13.8% of the population carrying a hemoglobinopathy-associated variant and substantial heterogeneity in distribution across ethnic groups and geographic regions. This review provides a comprehensive overview of the epidemiology, molecular characteristics, diagnostic strategies, treatment approaches, and prevention programs for β-thalassemia in Vietnam. Current evidence indicates that a limited number of recurrent HBB variants account for the majority of β-thalassemia alleles in the Vietnamese population, including codon 17 (A>T) (HBB: c.52A>T), codons 41/42 deletion (-TTCT) (HBB: c.126_129delTTCT), codons 71/72 (+A) (HBB: c.216_217insA), codons 95 (+A) (HBB: c.287_288insA), IVS-I-1 (G>T) (HBB: c.92+1G>T), IVS-I-5 (G>C) (HBB: c.92+5G>C), IVS-II-654 (G>T) (HBB: c.316+197C>T), -28 (A>G) (HBB: c.-78A>G), and -88 (C>T) (HBB: c.-138C>T). Diagnostic strategies generally follow a stepwise approach integrating hematological screening and hemoglobin analysis with confirmatory molecular testing. Advances in molecular diagnostics, particularly targeted polymerase chain reaction (PCR)-based assays and next-generation sequencing (NGS), have significantly improved detection of both carriers and affected individuals. Despite these advances, β-thalassemia continues to impose a considerable clinical, economic, and societal burden because many patients require lifelong blood transfusions, iron chelation therapy, and multidisciplinary management of disease-related complications. Major challenges include limited access to screening, prenatal diagnosis, and genetic counseling services, particularly in rural and ethnic minority populations, as well as the financial and technical barriers associated with advanced molecular diagnostics and emerging therapies. Strengthening nationwide screening programs, expanding access to prenatal and preconception genetic services, improving public awareness, and enhancing healthcare infrastructure are essential for reducing disease incidence and improving patient outcomes. In parallel, the integration of advanced molecular diagnostics and emerging gene-based therapies will be critical for advancing long-term disease control. This review highlights current knowledge gaps and proposes strategic priorities to support evidence-based policy development and comprehensive β-thalassemia prevention and management in Vietnam. Full article

(This article belongs to the Collection Feature Papers in Thalassemia Reports)

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13 pages, 694 KB

Open AccessArticle

Comparative Diagnostic Value of 3D Volumetry and Speckle-Tracking over Conventional 2D Echocardiography in the Evaluation of Left Ventricular Function in Pediatric Transfusion-Dependent Beta-Thalassemia

by Omar Raafat, Ahmed Salama Abouhay, Yasmine El Chazli, Yasser Wali and Hani Mahmoud Adel

Thalass. Rep. 2026, 16(2), 12; https://doi.org/10.3390/thalassrep16020012 - 19 Jun 2026

Abstract

Background: Left ventricular (LV) dysfunction remains the leading cause of mortality in transfusion-dependent beta-thalassemia (TDßT), yet conventional echocardiography often fails to detect early myocardial impairment. This study aimed to comprehensively evaluate LV function in children with TDßT using three-dimensional echocardiography (3DE) and speckle-tracking [...] Read more.

Background: Left ventricular (LV) dysfunction remains the leading cause of mortality in transfusion-dependent beta-thalassemia (TDßT), yet conventional echocardiography often fails to detect early myocardial impairment. This study aimed to comprehensively evaluate LV function in children with TDßT using three-dimensional echocardiography (3DE) and speckle-tracking strain analysis, comparing diagnostic performance with conventional two-dimensional (2D) parameters. Results: 50 TDßT patients were compared to 50 matched controls and exhibited preserved conventional LV ejection fraction (EF) on 2D (65.31 ± 7.12% vs. 69.21 ± 3.87%, p = 0.001), but 3DE revealed significant ventricular dilation with higher end-diastolic volume index (75.50 ± 17.99 vs. 65.63 ± 11.86 mL/m², p = 0.002) and end-systolic volume index (22.28 ± 7.85 vs. 18.21 ± 5.14 mL/m², p = 0.003). Despite preserved 3D EF (70.79 ± 5.98% vs. 72.07 ± 5.76%, p = 0.276), global longitudinal strain (GLS) was significantly impaired (−18.56 ± 2.37% vs. −21.47 ± 1.86%, p < 0.001). 3D volumetric parameters demonstrated superior diagnostic performance (AUC for LVEDVI Z-score = 0.874) compared to conventional indices. Transfusion duration correlated strongly with ventricular volumes (r = 0.569 for EDV, p < 0.001), while serum ferritin showed no significant correlation with cardiac parameters. Conclusions: Children with TDßT develop early subclinical LV dysfunction detectable by 3DE and strain analysis despite preserved conventional systolic indices. 3D volumetry and GLS should be integrated into routine cardiac surveillance protocols to enable timely therapeutic intervention. Full article

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15 pages, 610 KB

Open AccessArticle

Transfusion-Transmitted Risk: High Seroprevalence and Genotypic Diversity of Toxoplasma gondii in Thalassemia Major Calls for Donor Screening Policy Review

by Mitra Sadeghi, Mohammad Naderi Sorki, Bahareh Basirpour, Hossein Karami, Davood Anvari, Seyed Ali Shariatzadeh, Alireza Mohsennejad, Shahabeddin Sarvi, Shirzad Gholami, Seyed Abdollah Hosseini, Sara Gholami, Ahmad Daryani and Sargis. A. Aghayan

Thalass. Rep. 2026, 16(2), 11; https://doi.org/10.3390/thalassrep16020011 - 16 Jun 2026

Abstract

Objectives: Patients with thalassemia major are at high risk of developing blood-borne infections, including toxoplasmosis, due to their dependence on frequent blood transfusions and underlying immune system disorders. This study was designed to investigate this hidden risk and provide data for policymaking [...] Read more.

Objectives: Patients with thalassemia major are at high risk of developing blood-borne infections, including toxoplasmosis, due to their dependence on frequent blood transfusions and underlying immune system disorders. This study was designed to investigate this hidden risk and provide data for policymaking in blood transfusion services in a region with a high endemicity. Methods: A total of 300 blood samples from thalassemia patients in northern Iran were collected. Serological testing was conducted to detect IgG and IgM antibodies. DNA extraction followed, with molecular screening performed via PCR. Finally, genotyping of T. gondii was carried out using nested PCR focused on the GRA6 gene. Results: The serological analysis revealed 59.7% of patients exhibited IgG against T. gondii, while only 0.6% tested positive for IgM. The results of the molecular screening revealed 2.7% of patients had DNA of T. gondii. The results of genetic analysis showed 75% had type II, 12.5% had type I, and 12.5% belonged to type III. Conclusions: This study provides serological and molecular evidence of a high chronic Toxoplasma gondii burden in thalassemia patients from northern Iran, an endemic region. A significant association between blood transfusion history and seropositivity, along with parasite DNA detection, suggests elevated exposure risk, though direct transfusion transmission remains unproven. Finding’s support integrating nested PCR with routine serology for diagnosing infection in this population. Full article

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20 pages, 817 KB

Open AccessSystematic Review

Frequency of Thalassemias in the Brazilian Population and Comparison Between Diagnostic Methods: A Systematic Review

by Eliana A. Santos, Luciana S. Wermelinger and Renato S. Carvalho

Thalass. Rep. 2026, 16(2), 10; https://doi.org/10.3390/thalassrep16020010 - 5 Jun 2026

Abstract

Thalassemia is an inherited hemoglobin disorder caused by reduced or absent globin chain synthesis, with heterogeneous distribution worldwide and in Brazil. Back-ground/Objectives: This systematic review aimed to estimate the frequency of thalas-semia in the Brazilian population according to thalassemia type, geographic region, and [...] Read more.

Thalassemia is an inherited hemoglobin disorder caused by reduced or absent globin chain synthesis, with heterogeneous distribution worldwide and in Brazil. Back-ground/Objectives: This systematic review aimed to estimate the frequency of thalas-semia in the Brazilian population according to thalassemia type, geographic region, and population characteristics, as well as to evaluate the impact of diagnostic methods on frequency estimates. Methods: A systematic review was performed following PRISMA 2020 recommendations, in January 2026, including original studies conducted in Brazil-ian populations that reported thalassemia frequency data. Results: Thirty-six studies met the inclusion criteria, of which 77.8% were classified as high quality. The overall average frequency of thalassemia in Brazil was 7.5%, varying according to thalassemia type and diagnostic approach. The mean frequency of alpha thalassemia carriers was 12.3% (range: 5.5–54.0%), with regional variation from 5.79% in the Midwest to 17.3% in the Southeast. The −α^{3.7 kb} deletion was the most frequently reported mutation na-tionwide. Beta thalassemia showed a mean frequency of 2.81% (range: 0.24–18.1%), with regional values ranging from 0.59% in the Southeast to 12.2% in the North and a wide spectrum of pathogenic variants. Distinct frequency patterns were observed in populations with inherent interpretative bias, including individuals with sickle cell trait, systemic lupus erythematosus, microcytosis, and Black populations. Molecular diagnostic methods demonstrated higher sensitivity, enabling the detection of asymp-tomatic carriers and reducing false-negative results. Conclusions: These findings pro-vide a comprehensive epidemiological overview of thalassemia in Brazil and reinforce the importance of molecular diagnostics for accurate screening, genetic counseling, and the development of public health strategies. Full article

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12 pages, 396 KB

Open AccessArticle

Parental Perspectives on Prenatal Diagnosis and Termination of Pregnancy in Families Affected by β-Thalassemia in Pakistan: A Qualitative Study

by Iqra Javaid, Muhammad Ameeq and Muhammad Muneeb Hassan

Thalass. Rep. 2026, 16(2), 9; https://doi.org/10.3390/thalassrep16020009 - 9 May 2026

Abstract

Background: Advances in medical genetics and prenatal diagnosis have improved the detection of fetal abnormalities during pregnancy. The findings may lead some couples to consider termination of pregnancy (TOP). This study aimed to explore parental perspectives on prenatal diagnosis and termination of pregnancy [...] Read more.

Background: Advances in medical genetics and prenatal diagnosis have improved the detection of fetal abnormalities during pregnancy. The findings may lead some couples to consider termination of pregnancy (TOP). This study aimed to explore parental perspectives on prenatal diagnosis and termination of pregnancy among families in which both parents were β-thalassemia carriers and had at least one previously affected child. Methods: A qualitative study was conducted using semi-structured interviews with 30 participants (15 fathers and 15 mothers) recruited from Bahawal Victoria Hospital, Bahawalpur, Pakistan, between November 2024 and February 2025. Eligible couples were registered for chorionic villus sampling (CVS)-based prenatal diagnosis; both parents had confirmed β-thalassemia carrier status, and each family had at least one previously affected child with β-thalassemia major or intermedia. Interview data were analyzed using thematic analysis. Results: Religious beliefs, financial burden, prior experience with affected children, and partner support emerged as major influences on reproductive decision-making. Many parents viewed prenatal diagnosis as important for preparation and informed decision-making. Mothers more often described emotional conflict, stress, and reliance on support, whereas some fathers expressed greater acceptance of termination in the context of severe disease burden. Conclusions: Religious beliefs, prior disease experience, family dynamics, and socioeconomic pressures were important and interrelated influences on decisions about prenatal diagnosis and termination within this study population. Our findings underscore the importance of culturally sensitive, non-directive genetic counseling in low-resource settings. The study was limited by its small sample, single-center design, the use of joint spousal interviews, and the possibility that pre-interview counseling influenced participants’ responses. Full article

(This article belongs to the Section Conventional Treatment of Thalassemia)

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12 pages, 915 KB

Open AccessArticle

Association Between Plasma Cystatin C Concentration and Urine Osmolality in Adults with Different Forms of Beta-Thalassemia: A Cross-Sectional Study in Vietnam

by Loan Do Thi Thanh, Anh Nguyen Ngoc, Kien Nguyen Trung, Ha Nguyen Thi Thu, Dung Nguyen Huu and Thang Le Viet

Thalass. Rep. 2026, 16(2), 8; https://doi.org/10.3390/thalassrep16020008 - 6 May 2026

Abstract

Objective: To determine plasma cystatin C concentrations, urine osmolality and their relationship with disease severity in beta-thalassemia patients. Methods: A cross-sectional study was conducted on 234 patients with beta-thalassemia, including equal numbers (78 each) of beta-thalassemia major, intermedia, and minor cases, along with [...] Read more.

Objective: To determine plasma cystatin C concentrations, urine osmolality and their relationship with disease severity in beta-thalassemia patients. Methods: A cross-sectional study was conducted on 234 patients with beta-thalassemia, including equal numbers (78 each) of beta-thalassemia major, intermedia, and minor cases, along with 78 healthy individuals matched for age, sex, and body mass index, who served as the control group. Plasma cystatin C concentrations were quantified in all subjects using the ELISA method, and urine osmolality level was measured automatically on a FISKE 210 machine (USA). Results: The proportion of beta-thalassemia patients with increased plasma cystatin C concentration was 39.3% and the proportion with a decreased urine osmolality level was 67.5% compared with the control group. Plasma ferritin had predictive value for increased plasma cystatin C concentration (cut-off point: 567.5 ng/mL; AUC = 0.803) and decreased urine osmolality level (cut-off point: 488.15 ng/mL; AUC = 0.820), p < 0.001. Plasma cystatin C concentration increased gradually and urine osmolality level decreased gradually from minor beta-thalassemia to intermedia beta-thalassemia to major beta-thalassemia patients, with p < 0.001. Conclusions: Increased plasma cystatin C concentrations and decreased urine osmolality levels are common and are associated with severity in beta-thalassemia patients. Full article

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28 pages, 1280 KB

Open AccessReview

Recent Advances in Thalassemia Management: From Curative Therapies to Artificial Intelligence

by Mohamed Medhat Abdelwahab Gamaleldin, Shaimaa Mahmoud Nashat Sayed Abdelhalim and Ivo Abraham

Thalass. Rep. 2026, 16(2), 7; https://doi.org/10.3390/thalassrep16020007 - 22 Apr 2026

Abstract

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it [...] Read more.

Thalassemia is an inherited hemoglobin disorder characterized by chronic hemolytic anemia and substantial long-term healthcare needs. In β-thalassemia major, patients typically require regular red blood cell transfusions with iron chelation to prevent transfusional iron overload. Although supportive care has markedly improved survival, it is associated with a high treatment burden and does not provide a cure. In recent years, curative and disease-modifying therapies have expanded the treatment landscape. Allogeneic hematopoietic stem cell transplantation (HSCT) offers a potentially curative option for selected patients, while autologous gene therapy and gene-editing approaches have shown the capacity to achieve transfusion independence in clinical studies. In parallel, pharmacologic advances—including luspatercept, a transforming growth factor-beta (TGF-β) ligand trap—have been shown to enhance erythropoiesis and reduce transfusion requirements, and emerging agents such as fetal hemoglobin inducers (e.g., thalidomide) and the oral pyruvate kinase activator mitapivat have demonstrated clinically meaningful hemoglobin improvements in selected populations. Adjunctive strategies, including antioxidants, are under investigation to mitigate oxidative stress, and applications of artificial intelligence are increasingly used to support screening, diagnosis, and longitudinal monitoring of iron overload. This review synthesizes recent advances in curative therapies, novel pharmacologic agents, supportive strategies, and AI-enabled tools and highlights priorities for future clinical development and implementation. Full article

(This article belongs to the Collection Feature Papers in Thalassemia Reports)

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12 pages, 813 KB

Open AccessArticle

Implementing Genetic Counseling for Rare Diseases in LMICs: Pediatric and Prenatal Perspectives from India

by Siddannagoud, Dolat Singh Shekhawat, Kuldeep Singh, Varuna Vyas, Pratibha Singh, Charu Sharma, Navdeep Kaur Ghuman and Tanu Gupta

Thalass. Rep. 2026, 16(2), 6; https://doi.org/10.3390/thalassrep16020006 - 1 Apr 2026

Abstract

Background: This study investigated the clinical characteristics of consultands and examined their perceived personal control, satisfaction, and decision-making regarding genetic testing, as well as the factors influencing these outcomes, at a tertiary care center in northwestern India. Methods: Detailed clinical and family histories [...] Read more.

Background: This study investigated the clinical characteristics of consultands and examined their perceived personal control, satisfaction, and decision-making regarding genetic testing, as well as the factors influencing these outcomes, at a tertiary care center in northwestern India. Methods: Detailed clinical and family histories were recorded, and trained genetic professionals provided genetic counseling. Perceived personal control (PPC) was assessed pre- and post-counseling using the PPC (nine-item) questionnaire, while post-counseling satisfaction was measured using the six-item Genetic Counseling Satisfaction Scale (GCSS). Outcomes included awareness of genetic disorders, uptake of genetic testing, and reproductive decision-making. Results: A total of 225 consultands (125 pediatric and 100 antenatal) were enrolled. The most common systemic disorders were: inborn errors of metabolism (21.3%), congenital anomalies (15.2%), neurological disorders (15%), primary immunodeficiencies (12.3%), renal genetic disorders (12.2%), respiratory disorders (12%), thalassemia (9%), endocrine disorders (3.9%), and cardiovascular anomalies (3%). In the pediatric group, socioeconomic status (p = 0.048) and higher education levels (p = 0.02) were significantly associated with higher perceptions of adequate counseling time and overall GCSS. None of the examined factors in the prenatal group showed a statistically significant association with satisfaction scores. Consultands primarily concerned with preventing recurrence in future pregnancies showed significantly higher PPC scores both before (p = 0.026) and after counseling (p = 0.009), with the greatest overall improvement in satisfaction (p = 0.044). In the pediatric group, those with an affected family member showed the greatest post-counseling improvement in PPC. Conclusions: Low education, limited awareness, socioeconomic constraints, delayed presentation and low referral rates were key barriers to effective genetic counseling. Addressing these factors can improve consultand awareness, satisfaction, decision-making, and uptake of genetic testing, thereby enhancing reproductive outcomes in high-risk families. Full article

(This article belongs to the Section Quality of Life)

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9 pages, 247 KB

Open AccessArticle

Iron Overload and Endocrine Dysfunction in Adults with Transfusion-Dependent Beta-Thalassemia and Growth Retardation: A Correlational Study

by Muhammad Hammad, Sadaf Fardoos, Khadija Shakoor and Ali Nasir

Thalass. Rep. 2026, 16(1), 5; https://doi.org/10.3390/thalassrep16010005 - 11 Mar 2026

Abstract

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: [...] Read more.

Background and Objective: Iron overload remains a significant clinical concern in patients with transfusion-dependent beta-thalassemia (TDT). This study aims to characterize the iron load and endocrine profile of adult transfusion-dependent beta-thalassemia patients and to evaluate their correlation with growth retardation. Methods: A cross-sectional study was conducted at PIMS Hospital, Islamabad, involving 62 adult patients with homozygous or HbE beta-thalassemia receiving regular blood transfusions. Iron overload was assessed using serum ferritin (SF) and transferrin saturation (TS), while endocrine function was evaluated through measurements of thyroid-stimulating hormone-sensitive (TSH), free thyroxine (FT4), and insulin-like growth factor-1 (IGF-1). Data was analyzed using SPSS v26.0 and R v4.3.1, which included Pearson correlation, chi-square testing, and multivariable regression to explore associations between iron indices and endocrine dysfunction. Results: Serum ferritin demonstrated significant negative correlations with FT4 (r = −0.348, p = 0.005) and IGF-1 (r = −0.302, p = 0.015). MRI T2* pancreas values correlated positively with FT4 (r = 0.268, p = 0.037) and IGF-1 (r = 0.312, p = 0.015). Patients with ferritin > 5000 ng/mL exhibited a higher prevalence of low IGF-1 levels (89.2% vs. 64.0%, p = 0.018). No significant gender-based differences were observed in endocrine parameters. Conclusion: Pancreatic iron burden and elevated serum ferritin were significantly associated with impaired thyroid and growth axis function, highlighting the value of integrating MRI T2* and biochemical markers for early endocrine risk stratification in adult TDT patients. Full article

6 pages, 1310 KB

Open AccessBrief Report

Hemoglobinopathy Prevention Program in Immigrants: Equality Plus Education Program

by Duran Canatan, Vincenzo De Sanctis, Joan Lluis Vives Corrons, Giorgio Piacentini, Fatih Kara, Basak Tezel, Aslıhan Ugur Külekci, Özlem Zümrüt, Zekiye Özdemir, Kemal Gürsoy, Gamze Kaymak, Şirin Aydın, Tanju Altunsu, İlhan Aydın, Mustafa Hambolat, Nilgün Keloğlu, Elif Durmaz and Abdullah Solmaz

Thalass. Rep. 2026, 16(1), 4; https://doi.org/10.3390/thalassrep16010004 - 10 Mar 2026

Abstract

Background and aim: Hemoglobinopathies have become an important public health problem due to global migration. The aim of this project was to address the problem of hemoglobinopathy among immigrants living in Türkiye, Spain, and Italy, in addition to training health managers and Syrian [...] Read more.

Background and aim: Hemoglobinopathies have become an important public health problem due to global migration. The aim of this project was to address the problem of hemoglobinopathy among immigrants living in Türkiye, Spain, and Italy, in addition to training health managers and Syrian family physicians at immigrant health centers in the southeastern provinces of Türkiye. Material and methods: A three-year international project, named EQUALITY PLUS, was supported by the European Union Erasmus Project. We planned transnational meetings (TPM), vocational education meetings (VET), and Practical Implementation Meetings (PIEM) for the education program. Results: Four TPMs were held in Türkiye, Spain, and Italy, involving a total of 49 professionals. Two VETs were held in Spain and Italy. A total of 23 professionals attended both VETs. Six PIEMs were held in the southern and southeastern Turkish provinces, such as Adana Mersin, Hatay, Gaziantep, Kilis, and Sanliurfa. A total of 442 people, including 373 Syrian family physicians and 69 provincial health managers, were educated in six provinces in Türkiye. Discussion: While the immigrants to Italy and Spain come mainly from Central and North West African maritime routes, immigrants to Türkiye predominantly come from Syria. Among a total of 4 million Syrian immigrants to Türkiye, 200.000 were found to be carriers of thalassemia. In the refugee camps where Syrian immigrants live, the fertility rate is high and the number of sick newborns is increasing, and birth control, genetic counseling, and prenatal diagnosis methods are not sufficient. This project was intended to serve as a guide to prevent hemoglobinopathy in Syrian immigrants. Further projects are needed to address the fertility rate and increased number of sick newborns in these refugee camps. Family physicians at migrant health centers received training on the prevention of hemoglobinopathies. This training included providing detailed genetic counseling to families and providing prenatal diagnosis and preimplantation genetic diagnosis opportunities. Because of the major earthquake that occurred in this region after the project, the work could not continue and preliminary data could not be obtained. Public health services will follow the results of project and the registered number of sick newborns with hemoglobinopathies. Full article

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16 pages, 5310 KB

Open AccessArticle

Cascade Screening of β-Thalassemia in an Indian Family Using Flow Injection Analysis–Triple Quadrupole Mass Spectrometry: Comparison of Micro Sampling Approaches with Conventional Electrophoresis

by Ankitha K. Puthiyaveettil, Harshini K. Musuvathi and Deepalakshmi D. Putchen

Thalass. Rep. 2026, 16(1), 3; https://doi.org/10.3390/thalassrep16010003 - 24 Feb 2026

Abstract

Background: β-thalassemia is a rare genetic disorder affecting 1–5% of the global population and poses a health burden due to migration of individuals from endemic regions. Identifying asymptomatic β-thalassemia carriers is essential to prevent the birth of thalassemic babies. A simple, sensitive [...] Read more.

Background: β-thalassemia is a rare genetic disorder affecting 1–5% of the global population and poses a health burden due to migration of individuals from endemic regions. Identifying asymptomatic β-thalassemia carriers is essential to prevent the birth of thalassemic babies. A simple, sensitive method compatible with self-sampling could enhance the detection of β-thalassemia in the population. Methods: Capillary blood was collected via dried blood spot (DBS) and dried blood matrix (DBM) from 18 members (52.9%, 18/34) of a three-generation family. Hemoglobin was extracted, and globin chains were analyzed on a triple quadrupole mass spectrometer (TQMS). δ/β (%) was utilized as a biomarker to identify β-thalassemia. Venous blood collected from positive and negative individuals (n = 11) was further tested to confirm the findings and validated with complete blood count (CBC) and Capillary Electrophoresis (CE). Results: β-thalassemia was detected in seven individuals: three from generation I, three from generation II, and one from generation III. CBC showed thalassemia indices, while CE demonstrated elevated HbA2 consistent with β-thalassemia. Molecular sequencing of two samples confirmed the heterozygous c.92 + 5 G > C mutation in the β-globin gene. The overall prevalence of β-thalassemia in the family was 20.6% (7/34). High clinical performance was achieved across sample types, with 100% sensitivity for DBS, 100% specificity for DBM, and an overall accuracy of 91% when compared with CE. Conclusions: TQMS in combination with CBC parameters successfully identified asymptomatic heterozygous β-thalassemia carriers using self-sampling techniques. Cascade screening within affected families emerges as a possible strategy for early detection of β-thalassemia pending comprehensive validation. Full article

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7 pages, 980 KB

Open AccessCase Report

A Heterozygous ABCC6 Variant as a Potential Contributor to Choroidal Neovascularization in a β-Thalassemia Patient

by Debashis Pal, Dipankar Saha, Prosanto Kumar Chowdhury, Arup Das and Anupam Basu

Thalass. Rep. 2026, 16(1), 2; https://doi.org/10.3390/thalassrep16010002 - 29 Jan 2026

Abstract

β-thalassemia patients often experience ocular abnormalities such as angioid streaks (ASs), retinal pigmented epithelium degradation, visual field defects, and in rare instances choroidal neovascularization (CNV). Although ASs are common in individuals with hemoglobinopathies, the occurrence of choroidal neovascularization without preceding ASs is exceptionally [...] Read more.

β-thalassemia patients often experience ocular abnormalities such as angioid streaks (ASs), retinal pigmented epithelium degradation, visual field defects, and in rare instances choroidal neovascularization (CNV). Although ASs are common in individuals with hemoglobinopathies, the occurrence of choroidal neovascularization without preceding ASs is exceptionally rare. In this report, we describe a β-thalassemia patient who had developed CNV at the age of 27 years and also had experience of renal stones at the age of 19 years. He had undergone splenectomy and was under conservative therapy of iron supplementation. We conducted whole-exome sequencing (WES) in search of CNV-associated variants. Through variant filtering and Phenolyzer analysis, we have identified a rare heterozygous missense variant in the ABCC6 gene, ABCC6:NM_001171:exon25:c.3524T>C (rs376062004). In silico analysis revealed that this variant is present in the highly conserved region and is likely to decrease the stability of the protein. Mutation in the ABCC6 gene leads to pseudoxanthoma elasticum (PXE). Previously, it was believed that ASs and subsequent CNV-like ocular complication may develop due to the pathophysiological condition of thalassemia. However, our study provides compelling evidence that rare mutations in the ABCC6 gene, in combination with oxygen insufficiency, may contribute to the development of CNV in β-thalassemia patients. This finding highlights the potential genetic basis of PXE-mediated CNV development in β-thalassemia. Full article

(This article belongs to the Section Quality of Life)

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5 pages, 301 KB

Open AccessEditor’s ChoiceCase Report

The First Gene Therapy for Treating an Indonesian Child with Thalassemia Major: A New Hope for Indonesia

by Edi Setiawan Tehuteru, Teck Onn Lim, Anky Tri Rini Kusumaning Edhy, Ludi Dhyani Rahmartani, Stephen Diah Iskandar, Cresentia Irene, Rendi Prawira Gunawan, Reganedgary Jonlean and Grace Erdiana

Thalass. Rep. 2026, 16(1), 1; https://doi.org/10.3390/thalassrep16010001 - 19 Dec 2025

Cited by 1

Abstract

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to [...] Read more.

Background/Objectives: Thalassemia is highly prevalent in Indonesia, and its treatment imposes a significant financial burden. To date, thalassemia management in Indonesia remains largely limited to supportive therapies. This report aims to present the monitoring of the first Indonesian pediatric thalassemia patient to undergo gene therapy. Methods: Medical summaries were gathered across multiple time points. The gene therapy process consisted of several phases: screening, apheresis and cell manufacturing, conditioning, cell infusion, and post-treatment follow-up. The therapy utilized autologous CD34+ hematopoietic stem and progenitor cells (HSPCs), which were genetically modified using a lentiviral vector carrying the beta-globin gene. The primary outcome of this study was transfusion independence, determined through serial assessments of hematological parameters over a six-month period following gene therapy. Results: A 15-year-old female had been diagnosed with thalassemia major at the age of five. DNA analysis revealed compound heterozygous mutations Hb Malay (codon 19, AAC^Asn > AGC^Ser) and IVS1-nt5 (G > C). She had been receiving regular blood transfusions every 3–4 weeks, and hemosiderosis was detected in the liver and pancreas. Given the patient’s age—over 10 years—hematopoietic stem cell transplantation carries increased risks, making gene therapy the most suitable curative option. During the six-month follow-up period after gene therapy, the patient remained transfusion-independent and experienced no complications. Conclusions: In selecting an appropriate curative therapy for thalassemia patients, several factors must be considered. The successful implementation of the first gene therapy in an Indonesian pediatric thalassemia patient should serve as a catalyst for the continued development and expansion of curative treatment options for thalassemia patients across the country. Full article

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18 pages, 410 KB

Open AccessArticle

Epidemiological and Clinical Profile of Hemoglobinopathies and Thalassemia in Duhok, Kurdistan Region of Iraq: A Retrospective Study

by Burhan Abdullah Zaman, Zuhair Rushdi Mustafa, Delshad Abdulah Mohamed, Hasan Abdullah Aswad and Deldar Morad Abdulah

Thalass. Rep. 2025, 15(4), 12; https://doi.org/10.3390/thalassrep15040012 - 28 Nov 2025

Abstract

Background/Objectives: Thalassemia is among the most common hereditary disorders globally, characterized by impaired hemoglobin synthesis and ineffective erythropoiesis. This study analyzed data on hemoglobinopathies, with a particular focus on thalassemia, to support the development of a comprehensive national database and to improve understanding [...] Read more.

Background/Objectives: Thalassemia is among the most common hereditary disorders globally, characterized by impaired hemoglobin synthesis and ineffective erythropoiesis. This study analyzed data on hemoglobinopathies, with a particular focus on thalassemia, to support the development of a comprehensive national database and to improve understanding of the disease burden in the Kurdistan Region of Iraq. Methods: In this retrospective cross-sectional study, a total of 910 patients admitted to the region’s sole blood disorder center since its establishment were included. Results: The study analyzed 46.7% male and 53.3% female thalassemia patients in Duhok, with 58.46% reporting parental consanguinity. Hepatitis C virus (HCV) prevalence was 11.87%, while 8.90% underwent bone marrow transplantation (BMT) and 30.11% had splenectomies. Blood group distribution was O⁺ (36.26%), A⁺ (30.99%), and B⁺ (18.46%). Common medications included Deferasirox (34.62%), Hydroxyurea (26.70%), and Deferoxamine (5.82%), with 8.24% and 4.40% discontinuing Deferasirox and Hydroxyurea, respectively. Geographically, 29% of the patients originated from Duhok City, which exhibited a consanguinity rate of 18.65% (p = 0.020). The most prevalent conditions were β-thalassemia major (32.53%) and sickle cell anemia (24.73%). HCV-positive patients were predominantly diagnosed with β-thalassemia major (43.40%) and sickle cell anemia (33.96%). BMT recipients were mostly β-thalassemia major patients (80.25%), while splenectomy was common in β-thalassemia major (43.40%) and sickle cell β-thalassemia (22.64%). Vaccination rates included Pneumococcal (50.78%), Influenza (47.76%), and Hepatitis (39.08%, first dose). Six patients (0.66%) died, with 30.18% diagnosed before age 1 and 43.89% between 1 and 2 years. In conclusion, this study underscores the high prevalence of β-thalassemia major and sickle cell anemia in Duhok, with strong associations to parental consanguinity and low socioeconomic status. Gaps in early diagnosis and vaccination coverage remain significant challenges. Full article

(This article belongs to the Section Quality of Life)

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13 pages, 3457 KB

Open AccessArticle

Temporal Changes in Quality of Life and Psychological Burden of Patients with Thalassemia: A Comparative Data Analysis from 2018 to 2025

by Nikos Rikos, Marilena Tzagkaraki, Antigoni Linardaki, Maria Moloudaki and Manolis Linardakis

Thalass. Rep. 2025, 15(4), 11; https://doi.org/10.3390/thalassrep15040011 - 6 Nov 2025

Cited by 1

Abstract

Background/Objectives: Thalassemia significantly affects the mental well-being and lifestyle of patients and their families. This study evaluated the temporal changes in quality of life (QoL) and psychological burden among thalassemia patients in 2025 and in relation to 2018. Methods: Two cross-sectional samples of [...] Read more.

Background/Objectives: Thalassemia significantly affects the mental well-being and lifestyle of patients and their families. This study evaluated the temporal changes in quality of life (QoL) and psychological burden among thalassemia patients in 2025 and in relation to 2018. Methods: Two cross-sectional samples of patients (n = 236) were recruited during 2025 (n₁ = 117) and 2018 (n₂ = 119) at the Thalassemia Units on Crete/Greece. The EQ-5D-3L Quality of Life Scale, the EQ VAS Index, and the Hospital Anxiety and Depression Scale (HADS) were used through multiple logistic regression analysis to assess relative parameters. Results: High mean Health Status (EQ VAS Index) and QoL scores remained consistent from 2018 to 2025, anxiety mean levels were low and remained consistent from 2018 to 2025, depression levels were low but higher in 2025 in relation to 2018 (p = 0.041), anxiety significantly exceeded depression in both 2018 and 2025, better QoL was associated with improved health status and reduced anxiety and depression, and individuals with children exhibited significantly lower odds of experiencing low or moderate QoL. Conversely, each unit increase in the Anxiety score significantly increased the odds of low or moderate QoL (OR = 1.26, p = 0.002). Similarly, each unit improvement in health status significantly reduced the odds of low or moderate QoL (OR = 0.97, p = 0.009). Conclusions: Health status and QoL remained consistent from 2018 to 2025, while depression levels increased. Anxiety significantly exceeded depression, and better QoL was associated with improved health status and reduced anxiety and depression. Full article

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16 pages, 716 KB

Open AccessReview

The Interplay Between β-Thalassemia and the Human Virome: Immune Dysregulation, Viral Reactivation, and Clinical Implications

by Didar Hossain and Mohammad Jakir Hosen

Thalass. Rep. 2025, 15(4), 10; https://doi.org/10.3390/thalassrep15040010 - 3 Oct 2025

Abstract

β-thalassemia is a chronic genetic blood disorder characterized by defective β-globin synthesis, requiring frequent transfusions and resulting in iron overload, immune dysfunction, and increased susceptibility to infections. In these immunocompromised patients, altered immune responses lead to significant changes in the human virome, promoting [...] Read more.

β-thalassemia is a chronic genetic blood disorder characterized by defective β-globin synthesis, requiring frequent transfusions and resulting in iron overload, immune dysfunction, and increased susceptibility to infections. In these immunocompromised patients, altered immune responses lead to significant changes in the human virome, promoting viral persistence, reactivation, and expansion of pathogenic viral communities. This review explores the intricate relationship between β-thalassemia and the human virome, focusing on how clinical interventions and immune abnormalities reshape viral dynamics, persistence, and pathogenicity. Patients with β-thalassemia exhibit profound innate and adaptive immune dysregulation, including neutrophil dysfunction, T cell senescence, impaired B cell and NK cell activity, and expansion of myeloid-derived suppressor cells. These alterations create an immunological niche that favors viral reactivation and virome expansion. Iron overload enhances viral replication, while chronic transfusions introduce transfusion-transmitted viruses. Splenectomy and allo-HSCT further compromise viral surveillance. Additionally, disruptions in the gut virome, particularly bacteriophage-driven dysbiosis, may exacerbate inflammation and impair host–virus homeostasis. The human virome is not a passive bystander but a dynamic player in the pathophysiology of β-thalassemia. Understanding virome–immune interactions may offer novel insights for infection monitoring, risk stratification, and precision therapies in thalassemic patients. Full article

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10 pages, 919 KB

Open AccessArticle

Comparing Spectrophotometric Hemoglobin Concentrations with Conventional Laboratory Cell Analyzers in Transfusion-Dependent Beta-Thalassemia Patients

by Khaled Yassen, Nawal Omar, Abdulaziz Bushehab, Renad AlSubaie, Lina AlMudayris, Sara A. Albunyan, Shaima AlAkroush, Sherif Saleh, Dur I. Shahwar and Ossama Zakaria

Thalass. Rep. 2025, 15(3), 9; https://doi.org/10.3390/thalassrep15030009 - 10 Sep 2025

Abstract

Background/Objectives: Thalassemias, a hereditary condition commonly linked to chronic anemia, require regular blood transfusions and repeated blood draws for assessments of hemoglobin (Hb) content, which can be uncomfortable. A promising substitute for laboratory hemoglobin testing is non-invasive spectrophotometric hemoglobin (SpHb) monitoring; however, its [...] Read more.

Background/Objectives: Thalassemias, a hereditary condition commonly linked to chronic anemia, require regular blood transfusions and repeated blood draws for assessments of hemoglobin (Hb) content, which can be uncomfortable. A promising substitute for laboratory hemoglobin testing is non-invasive spectrophotometric hemoglobin (SpHb) monitoring; however, its applicability particularly among blood transfusion-dependent thalassaemic patients needs to be investigated. This study’s primary goal was to investigate the relationships and agreements between SpHb, g/dL, and an automated hematology analyzer (Hb, g/dL) in this particular patient population. The secondary goal was to track how blood transfusions affect SpHb, g/dL, laboratory Hb, and pleth variability index (PVI, %). Methods: In this study, sixty patients were included. A Masimo Radical-7 pulse CO-oximeter was used to measure the SpHb, and a Sysmex XN-1000 hematological analyzer measured the laboratory Hb. Results: The results revealed a significant correlation between SpHb and laboratory Hb (n = 108, r = 0.587, p < 0.001) but also demonstrated that SpHb consistently overestimated laboratory Hb levels, with a mean bias of −1.18 g/dL (95% CI: −1.4344 to −0.9267). The Bland–Altman analysis showed a good degree of reliability between this bias (SpHb–Hb) and laboratory Hb (g/dL), with an Intra Class Correlation (ICC) of 0.613 but with a wide 95% CI ranging from 0.557 to 0.736 (t = 3.817, p < 0.001). The 95% limits of agreement ranged from −3.7893 to +1.4228 g/dL. Conclusions: This significant bias restricted the application of SpHb as a trustworthy method for assessing hemoglobin levels in patients with blood transfusion-dependent thalassemia. Nonetheless, the capability to monitor SpHb and PVI variations during blood transfusions offered a real-time assessment of the impact of transfusions on patients’ hemoglobin levels and volume status. Full article

(This article belongs to the Section Quality of Life)

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8 pages, 216 KB

Open AccessArticle

The Distribution of HLA Alleles in Patients with Beta Thalassemia

by Yasin Yilmaz, Zeynep Karakas, Ayse Erol Bozkurt, Demet Kivanc, Mediha Suleymanoglu, Hayriye Senturk Ciftci, Cigdem Kekik Cinar and Fatma Savran Oguz

Thalass. Rep. 2025, 15(3), 8; https://doi.org/10.3390/thalassrep15030008 - 27 Aug 2025

Abstract

Background: It has been shown that human leucocyte antigen (HLA) alleles are related to certain diseases. Some alleles were associated with alloimmunization in individuals with thalassemia. In this study, we studied the distribution of HLA alleles among beta thalassemia (BT) patients compared to [...] Read more.

Background: It has been shown that human leucocyte antigen (HLA) alleles are related to certain diseases. Some alleles were associated with alloimmunization in individuals with thalassemia. In this study, we studied the distribution of HLA alleles among beta thalassemia (BT) patients compared to healthy controls. Material and Methods: The HLA results of 100 patients with BT and 100 healthy controls were obtained for the study. The HLA-A, -B and -DRB1 tissue typing were performed at the laboratory. The low-resolution sequence-specific primer (SSP)–polymerase chain reaction (PCR-SSP) (Olerup HLA-A,B,DR typing kit, USA) and sequence-specific oligonucleotide (SSO)–PCR (LABType HLA-A,B,DR kit, ABD) methods were performed using the Luminex genotyping kits. All related data were retrospectively analyzed. Results: One in five patients (21%) underwent hematopoietic stem cell transplantation (HSCT). Patients with HSCT had significantly lower frequency of HLA-B *14, HLA-DRB1 *11 and HLA-DRB1 *16 alleles and had a higher frequency of HLA-A *66, HLA-B *41, HLA-B *55, HLA-DRB1 *3 alleles compared to patients without HSCT (p < 0.05). The HLA-A *3, HLA-B *41 and HLA-B *55 alleles were more commonly seen in HSCT patients compared to the healthy group (p = 0.04). Female patients showed a higher frequency of HLA-B *58 and HLA-DRB1 *4 alleles (p = 0.04). Conclusions: This study demonstrated that HLA-B *41 and -B *55 alleles were closely related to HSCT among BT patients. It might be considered that the variance in certain HLA-B alleles in BT patients might cause difficulty in finding a matched donor in this limited population. Full article

(This article belongs to the Section Innovative Treatment of Thalassemia)

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