Beta-thalassemia Carriers Research Articles

Genetic Study for Identifying Beta Thalassemia Trait in Relatives of Children with Beta Thalassemia Major.

The most common inherited illness, thalassemia, is thought to have a detrimental effect on public health, particularly in endemic areas. Children with beta thalassemia disease have several mutations. Prevention and premarital examination are still the most effective measures to lessen the burden of beta thalassemia. This study primarily aimed to determine the beta thalassemia carriers in relatives of beta thalassemia major children, the role of gene study in the confirmation of beta thalassemia trait diagnosis, and to detect the genetic defect in the relatives of beta thalassemia major children. The cross-sectional study was conducted on 109 healthy children, aged between six months and 18 years, who were the relatives (second and fourth degree) of beta thalassemia major cases. Gene screening, using the amplification refractory mutation system (ARMS) polymerase chain reaction (PCR), covered the most common 22 alleles in the Mediterranean region, and was successful in detecting 61.5% of beta-globin chain mutations of studied participants, in addition to high prevalence (34.8%) of beta thalassemia carriers among the relatives of beta thalassemia children. The beta thalassemia carrier rate was found to be highly prevalent among relatives of beta thalassemia major children. Despite the accuracy of gene screening in the detection of beta thalassemia carriers, the use of the most common 22 alleles can only detect 61.5% of carriers; hence, the value of tested gene study is still limited in the detection of carrier rates.

Loss-of-Function Variants in SUPT5H as Modifying Factors in Beta-Thalassemia.

It is well known that modifiers play a role in ameliorating or exacerbating disease phenotypes in patients and carriers of recessively inherited disorders such as sickle cell disease and thalassemia. Here, we give an overview of the literature concerning a recently described association in carriers of SUPT5H Loss-of-Function variants with a beta-thalassemia-like phenotype including the characteristic elevated levels of HbA2. That SUPT5H acts as modifier in beta-thalassemia carriers became evident from three reported cases in whom combined heterozygosity of SUPT5H and HBB gene variants was observed to resemble a mild beta-thalassemia intermedia phenotype. The different SUPT5H variants and hematologic parameters reported are collected and reviewed to provide insight into the possible effects on hematologic expression, as well as potential disease mechanisms in carriers and patients.

Social and Cultural Influences on Genetic Counseling Acceptability: A Mixed-Methods Study on Beta-Thalassemia Carriers Among Graduate Students in West Bengal, India.

Thalassemia is an inherited blood disorder characterized by abnormal production of hemoglobin. The prevalence of thalassemia in India varies depending on the region and population. The study used a pre- and postcounseling cross-sectional design, which involves measuring outcomes before and after the intervention (genetic counseling). Three hundred and eighty-five respondents were screened as thalassemia carriers, between a pool of 2985 participants to depict the quantitative prevalence of thalassemia. Two separate qualitative cross-sectional studies were conducted and compared to validate genetic counseling. The aims of the study are to contribute to the understanding of thalassemia carrier frequency and to improve the education and awareness of college students regarding thalassemia. Two different questionnaires were used with the same knowledge, attitude, and practice parameters, one before and one after counseling. A two-sample t-test and an analysis of variance (ANOVA) F-test were used to compare the changes in knowledge, attitude, and practice. Using paired samples t-test to compare the pre- and postcounseling outcome showed significant (P < 0.001) elevation in terms of knowledge, attitude, social beliefs, social discomfort, and practice as a thalassemia carrier. Further, ANOVA F-test demonstrates the relationship between demography and the difference in parametric score of the pre- and postcounseling outcome. By improving knowledge and attitudes, counseling can help individuals to better understand their condition and the importance of adhering to treatment recommendations. This can lead to improved health outcomes and a better quality of life for affected individuals.

Serum Iron and Ferritin Levels in Beta Thalassemia Carriers in Duhok Governorate, Iraq.

Background Thalassemia and iron deficiency anemia (IDA) account for most cases of microcytic hypochromic anemia. It is a common misconception that iron deficiency does not occur in thalassemia. However, studies have found that iron deficiency can coexist in carriers of beta thalassemia. Objective The aim of this study was to determine the prevalence of iron deficiency and iron overload in carriers of beta thalassemia in Duhok, Iraq. Patients and methods This prospective cross-sectional study included 250 patients with beta thalassemia carriers attending Kurdistan Private Hospital Laboratory Department from July 2021 to June 2023. Patients with microcytic hypochromic blood picture were tested for HbA2 levels, and those with a level >3.7% were included in the study and were tested for serum iron and serum ferritin levels. Results The age range was 15-80 years, with a mean of 25 years, and the male-to-female ratio was 1.5:1. The prevalence of iron deficiency in beta thalassemia carriers was 16% (N = 40). The prevalence of iron overload was 8.4% (N = 21). There was a significant statistical difference among those with iron deficiency, normal iron status, and iron overload in terms of hemoglobin level (P=0.001), RBC count (P=0.012), HbA2 (P=0.015), and serum ferritin (P < 0.0001). Conclusion Iron deficiency is more prevalent in beta thalassemia carriers than iron overload, necessitating proper assessment of iron status in patients with beta thalassemia carriers. Those with abnormal iron status need effective treatment to optimize the overall outcomes in patients with beta thalassemia carriers.

Exploring the Clinical and Hematological Characteristics of Beta-Thalassemia Trait: A Comprehensive Analysis in a Tertiary Care Hospital Setting.

Beta-thalassemia is one of the most common inherited hematological diseases caused by more than 350 mutations in the β-globingene (HBB). Beta-thalassemia carrier or trait is associated with defects in one allele of the HBB gene. The majority of beta-thalassemia trait cases remain concealed in society and remain unnoticed as they are mostly asymptomatic or present with mild symptoms of anemia. There is a 25% chance of having children with beta-thalassemia major and a 50% chance of having carrier babies when two people with beta-thalassemia trait are married. Hence, it is important to identify the individuals with beta-thalassemia trait and provide counseling to understand the risks of pregnancy and its outcome. Aim To study the identification of beta-thalassemia trait cases along with their clinical findings and hematological correlation. Materials and methods Study Design This was a retrospective study conducted at Saveetha Medical College and Hospitalfor a period of four years from January 2020 to December 2023. Inclusion Criteria Age group more than 18 years, antenatal mother, cases of anemia who were refractory to iron treatment, and screening of family members in the positive cases of beta-thalassemia trait. Exclusion Criteria History of blood transfusion within three months was excluded. Data Collection A total number of 837 cases were screened to rule out the presence of beta-thalassemia trait/hemoglobin (Hb) variants. A 2 mL of intravenous blood samples were collected in an ethylene diamine tetraacetic acid (EDTA) vacutainer tube and processed in a Sysmex XN 1000 (Hyogo, Japan: Sysmex Corporation)automated hematology analyzer. The hematological parameters were analyzed. Statistical Analysis The study included both descriptive and analytical characteristics. Mean and standard deviation (SD) were calculated for all the hematological parameters. Beta-thalassemia trait was diagnosed with an HbA2 level of more than 4.0% through high-performance liquid chromatography (HPLC) analysis. Results Among the 837 samples studied for HPLC screening, 74 (8.8%) cases were found to have beta-thalassemia trait. The age group included was from 18 years to 56 years. Of 74 cases studied, 32(43%) were females and 42(57%) were males. Among the 74 cases studied, the Mentzer index <13 was seen in 58 (78%) cases and the Mentzer index >13 was seen in 16 cases (22%). Thirty-four cases (46%) of beta-thalassemia traits presented to the hospital with a history of fever for evaluation and antenatal screening accounted for 19 cases (26%). The mean red blood cell (RBC) count was 5.5 million/cu.mm; mean corpuscular volume (MCV) was 63.8 fL; mean corpuscular hemoglobin (MCH) was 19.6 pg; red cell distribution width coefficient of variation (RDW-CV) was 17.8%. Among the 74 cases studied, 37(46%) cases had an Hb of more than 11 g/dL, 22 cases had mild anemia, 12 cases had moderate anemia, and three cases had severe anemia. Conclusion This study concluded that regular monitoring of the Mentzer index along with HPLC analysis is an effective approach in identifying beta-thalassemia trait cases and further providing genetic counseling among the couples that will help in reducing high-risk pregnancy and the birth of a child with thalassemia major.

Evaluation of reticulocyte indices and mathematical formulas for beta-thalassemia carriers screening among Egyptian beta-thalassemia patients’ families

Background Egypt lies within the global thalassemia belt, where beta-thalassemia presents a notable socioeconomic burden. Patients and methods One hundred fifty-seven relatives of beta-thalassemia patients were included in this cross-sectional study. It aimed to ascertain a cost-efficient and accurate screening approach for identifying beta-thalassemia carriers (BTC) by evaluating some erythrocyte and reticulocyte parameters measured on Advia 2120 analyzer (Siemens) and assessing four mathematical Formulas (Metzner index, Green and King et al., Roth et al., and Vicinanza et al. formulas). Results Participants were stratified into distinct categories: BTC (42%), normal (24.2%), mild iron-deficiency anemia (IDA) (17.2%), severe IDA (3.8%), and a subset with both IDA and BTC (mix group) accounting for 12.7%. Receiver operating characteristic curve analysis identified absolute reticulocyte count as the optimal discriminator (area under a curve=0.837) between BTC and IDA. The Mentzer index and Green and King et al. formula demonstrated superior diagnostic utility among the evaluated formulas. However, none of the formulas effectively distinguished between BTC and the mix group, a frequently overlooked and challenging group for diagnosis. Interestingly, our data highlighted absolute reticulocyte count and percentage as the sole parameters capable of distinguishing BTC from the mix group. Consequently, two algorithms were developed. The first one had a good agreement (κ=0.62) with 77.3% concordance, while the second one demonstrated improved screening performance (κ=0.66) with 79.8% agreement. Conclusion The optimal screening strategy involves distinguishing between various categories of both IDA and BTC. Our algorithms, designed as a low-cost and user-friendly mass screening tool, may serve this purpose effectively.

Fuzzy-Based Fusion Model for β-Thalassemia Carriers Prediction Using Machine Learning Technique

The abnormality of haemoglobin in the human body is the fundamental cause of thalassemia disease. Thalassemia is considered a common genetic blood condition that has received extensive investigation in medical research globally. Likely, inherited disorders will be passed down to children from their parents. If both parents are beta Thalassemia carriers, 25% of their children will have intermediate or major beta thalassemia, which is fatal. An efficient method of beta thalassemia is prenatal screening after couples have received counselling. Identifying Thalassemia carriers involves a costly, time-consuming, and specialized test using quantifiable blood features. However, cost-effective and speedy screening methods must be developed to address this issue. The demise rate due to thalassemia development is outstandingly high around the globe. The passing rate due to thalassemia development can be reduced by following the proper procedure early; otherwise, it significantly impacts the body. A machine learning-based late fusion model proposes the detection of beta-thalassemia carriers by analyzing red blood cells. This study applied the late fusion technique to employ four machine learning algorithms. For identifying the beta-thalassemia carriers, logistics regression, Naïve Bayes, decision tree, and neural network have achieved an accuracy of 94.01%, 93.15%, 97.93%, and 98.07%, respectively, by using the features-based dataset. The late fusion-based ML model achieved an overall accuracy of 96% for detecting beta-thalassemia carriers. The proposed late fusion model performs better than previously published approaches regarding efficiency, reliability, and precision.

Common mutation analysis of beta-thalassemia carriers by amplification refractory mutation system-polymerase chain reaction in cases diagnosed by capillary zone electrophoresis at National Public Health Laboratory, Nepal

Abstract BACKGROUND: Beta (β)-thalassemia is a globally prevalent genetic disorder with over 350 known mutations in the β-globin gene. Intervening-sequence (IVS) 1–5 (G→C), 619 bp deletion, IVS 1–1 (G →T), C-15 (G→A), frameshift (FS) 41/42 (−CTTT), FS 8/9 (+G), codon 19, A-G, and codon 17 (A→T) are some common mutations in β-thalassemia. This study aimed to identify and analyze the common mutation by amplification refractory mutation system polymerase chain reaction in β-thalassemia carriers diagnosed by capillary zone electrophoresis (CZE) at National Public Health Laboratory. MATERIALS AND METHODS: On the basis of archived data, the CZE performed on 781 samples between June 2019 and July 2022 was analyzed. Without regard to age, gender, race, or address, 121 samples were ultimately selected for mutation analysis during this time because they were identified as positive for the β-thalassemia traits based on high HbA2 levels of more than 3.5%. RESULTS: IVS 1–5 (G→C) was the most common mutation followed by 619 bp deletion. Five mutations namely IVS 1–5 (G→C), 619 bp deletion, FS 41/42 (−TTCT), FS 8/9 (+G), and codon 15 (G→A) accounted for 84.3% of cases. A single mutation was seen in 87 cases (71.9%), more than one mutation in 15 cases (12.4%) whereas 19 cases (15.7%) did not show any of the mutations tested. CONCLUSION: IVS 1–5 (G-C) is the most prevalent mutation in Southeast Asian nations, with the 619 bp deletion predominant in the Tharu community. Further research is needed to understand diverse ethnic groups and regions, enabling prenatal diagnostics and genetic counseling for β-thalassemia prevention.

Effect of Iron replacement therapy in Pregnant Beta Thalassemia Carrier Patients with Coexisting Iron Deficiency Anemia.

Iron deficiency anemia (IDA) and β -Thalassemia trait are two prevalent etiologies of microcytic hypochromic anemia. Pregnant women with IDA face significant risk of short-term and long-term complications for mother and newborns. The incidence of concurrent thalassaemia trait and iron deficiency was reported to be quite high but despite the high prevalence of these two conditions, the diagnosis is often underestimated and not properly managed.&#x0D; OBJECTIVE; The present study was conducted to evaluate impact of iron therapy in pregnant beta thalassemia minor patients with iron deficiency anemia.&#x0D; METHODS; Study Group constitutes 60 beta thalassemia trait pregnant women with iron deficiency anemia (IDA) with Hb less than 11g/dl, HbA2 levels &gt;3.5% on HPLC and low serum ferritin (&lt;30 ng/mL).After the initial investigations, participants received iron supplementation as 60 mg elemental iron three times daily for duration of 8 weeks. After completing therapy, complete blood count and serum ferritin were performed.&#x0D; RESULTS; Iron replacement therapy results in effective increment in hemoglobin, red cell indices and Serum ferritin.&#x0D; CONCLUSION; Pregnant women with beta-thalassemia minor combined with IDA can receive Iron replacement therapy for improvement in Hemoglobin effectively.

Prevalence of beta thalassemia carriers in India: a systematic review and meta-analysis.

A large number of studies have reported that the prevalence of beta thalassemia carriers in India varies by ethnic groups. The objective of this study was to conduct a systematic review of the published studies and conduct a meta-analysis to determine the prevalence of beta thalassaemia carriers in India. A PubMed database search using keywords "beta thalassaemia AND India" identified 1088 articles of which 69 articles were included in the review. Studies using diagnostic tests and methods recommended by the International Council for Standardization in Haematology were used for calculation of pooled prevalence. Pooled prevalence was calculated using a random effects model using Review Manager version 5.3. Studies had screened five categories of populations, that is, the general population; tribal groups, communities not belonging to tribal groups, persons with anemia, and persons referred with a suspicion of hemoglobinopathy. This heterogeneity contributed to a high pooled prevalence of beta thalassemia carriers of 8.23% (95% CI 7.36-9.10). Sub-group analysis however yielded 3.74% (95% CI 2.52-4.97) pooled prevalence of beta thalassemia carriers in the general population. It was 4.6% (95% CI 3.2-6.2) among tribal groups. Quality of prevalence studies was limited by methodological issues including non-random sampling methods, heterogeneity of population types screened, and lack of use of recommended diagnostic cut-offs. Prevalence of beta thalassemia carriers was similar in tribal populations and the general population, indicating the need to further investigate the prevalence of beta thalassemia carriers in tribal groups.

Efficacy of Education in Providing Knowledge about Thalassemia Prevention and Family Screening of Thalassemic Patients

Objective: The purpose of this study was to track out Beta Thalassemia carriers in affected households and evaluate the efficacy of thalassemia awareness campaigns. Study Design: Observational - Cross-Sectional study Place and Duration: Department of Pathology &amp; Diagnostic and Research Laboratory - LUMHS Hyderabad/Jamshoro. 01-09-2021 to 31-03-2022 Methods: A total of 55 thalassemia patients and families included in the study after providing written consent; the research was conducted at the Department of Pathology and Diagnostic and Research Laboratory. Demographic information such as age, gender, education level, and family history of thalassemia was recorded, and SPSS 24.0 was used for statistical analysis. Results: In 55 patients, majority 33 (60%) were males and 22 (40%) were females. The frequency of bimonthly blood transfusions was found to be the lowest, and consanguineous marriage between parents was found in 46 (83.6%) of patients. Three (5.5%) siblings of thalassemia patients were found to have thalassemia major, and seventeen (34.5%) siblings were found to have thalassemia minor. Thirty-five (63.6% of patients) were found to have a normal electrophoresis pattern. Conclusion: The research showed that roughly 50% of families were impacted by thalassemia and that 25% of individuals had previously received a blood transfusion. The instructional event was evaluated positively for its impact on participants' understanding of thalassemia. Keywords: Effectiveness of Educational Awareness, Carriers, Thalassemia, family history

Comparison of HbA2 Using High Performance Liquid Chromatography Versus Haemoglobin Capillary Zone Electrophoresis.

Thalassemia is among the most common hereditary disorders in the world. Approximately 5% of the world's population are carriers of hemoglobinopathies, and 2.9% are carriers of beta thalassemia. Haemoglobin A2 (HbA2) constitutes less than 3% of the total hemoglobin (Hb) in adults, and the determination of Hb A2 levels is important to diagnose the beta thalassemia trait(BTT). In some cases, the level of HbA2 is not typically elevated, and some difficulties may arise in making the diagnosis. Cation exchange high-performance liquid chromatography (HPLC) and HbCZE (haemoglobin capillary zone electrophoresis) are considered acceptable methods to diagnose BTT, but these vary in their accuracy and cut-offs. In this study, we attempted to compare HbA2 values using two methods, HPLC and HbCZE, in 536 whole blood samples sent by physician-ordered hemoglobinopathy screening over two years. This included antenatal women, patients with anemia not responding to iron, and cases of familial screening where either a child or a sibling had been diagnosed with hemoglobinopathy or thalassemia. The performance characteristics of both machines were compared for the detection of the 5 most common hemoglobin variants: Hb A, HbF, HbS, Hb C, and HbE. On comparing the HbA2 values, the HPLC showed higher values for HbA2 as compared to HbCZE, while the HbF and HbS measurement agreement was good between both methods. Normal ranges and mean normal values of HbA2 differ between different methods and different manufacturers; hence, each institute using these machines should validate its cutoffs.

DIAGNOSTIC ACCURACY OF RDWI TO DIFFERENTIATE IRON DEFICIENCY ANEMIA AND THALASSEMIA TRAIT IN BORDERLINE HBA2

Background: Thalassemia is an inherited hemoglobin disorders in which there is reduction or absence of α or β chains due to mutations in α or β genes. Microcytic hypochromic anemia is hallmark of beta thalassemia trait and the patient is usually asymptomatic. It is important to differentiate it from iron deficiency anemia (IDA) which also shows similar peripheral blood picture. The diagnosis is based on quantification of HbA2 and serum ferritin. If the level of HbA2 is more than 3. 5%, then diagnosis of beta thalassemia trait is made. The problem arises with borderline HbA2 i. e 3.1% - 3.4%. There is also diagnostic difficulty when concomitant iron deficiency anemia is present.&#x0D; Objectives: To determine the diagnostic accuracy of RDWI in borderline HbA2 to distinguish the beta thalassemia trait from IDA and to diagnose beta thalassemia trait when genetic analysis is not easily available.&#x0D; Methods: It was a cross sectional validation study. A total of 90 patients were included in this study, having HbA2 between 3.1-3.4%. Tests for serum ferritin, serum iron and total iron binding capacity (TIBC) were done on all samples. RBC morphology, RBC count, mean cell volume (MCV), mean cell hemoglobin (MCH), mean cell hemoglobin concentration (MCHC) and RDW of all samples were noted. RDWI of all samples was calculated. Mutational analysis by ARMS- PCR was done for confirmation of β thalassemia trait.&#x0D; Results: Out of 90 samples with borderline HbA2, 30 cases were diagnosed as β thalassemia trait. Out of these, 15(50 %) had concomitant IDA along with beta thalassemia trait and 15 were non iron deficient beta thalassemia carriers. 43 samples were not iron deficient and were also negative for β thalassemia trait, whereas 17 samples had only IDA without beta thalassemia trait. The sensitivity of RDWI was 76.6% and specificity was 56.6% in borderline HbA2.&#x0D; Conclusion: RDWI is a good indicator to differentiate between IDA and beta thalassemia trait (sensitivity 76.6% specificity 56.6%). But in all cases of borderline HbA2 genetic analysis should be done to see the mutation and to confirm the diagnosis.

Beta Thalassemia Carrier Rate: Problem Burden among High School Children.

A cross-sectional multicenter study was carried out on 4320 randomly selected students from four governorates of the Nile Delta region, Egypt. All patients were to be tested for their complete blood count. Those with microcytic hypochromic anemia not caused by iron deficiency were tested for βT carrier status using high-performance liquid chromatography. The total prevalence of βT carrier rate was 6.13%. The highest prevalence was detected in Al-Sharkia Governorate, reaching 7.89%, followed by 6.90% in Al-Gharbia Governorate. Al- Dakahilia and Al-Menoufia showed lower rates of 4.86% and 3.73%, respectively. Despite the premarital national screening program for βT in Egypt, the carrier rate is still high. More effort should be done into the proper implementation of national prevention programs.

5610480 TRANSFORMATION OF THALASSAEMIA GENETIC TESTING BY THE IMPLEMENTATION OF NGS-BASED THALASSEMIA ASSAY

Background: The haemoglobinopathies, are the most common monogenic diseases worldwide, and have been recognized as a growing global health challenge. Thalassemia is a serious health problem in Cyprus where 12 % of the population are carriers of beta-thalassaemia and about 19% are carriers of alpha-thalassaemia[1]. Because of the high incidence of the disease and the heavy impact on the health care system, the Cyprus National Prevention Programme was initiated and is successfully running since 1978. The traditional strategy for thalassaemia molecular diagnosis was designed either to identify only the most common mutations, or to target the main causing genes of thalassaemia, HBA, and HBB by conventional molecular techniques such as PCR, Real-Time PCR, MLPA, Sanger sequencing, and Mini sequencing. The complex analysis with the use of multiple different techniques to obtain a result, can cause prolonged turn-around times and costly processes and may even not be conclusive. Aim: The aim is to replace the laborious conventional molecular testing with a comprehensive analysis of the thalassaemias by the establishment of an NGS-based test for the simultaneous genetic analysis of all variants on both HBA and HBB gene clusters. Methods: A commercial CE-IVD NGS Thalassemia kit, that detects all sequence variants in HBA1, HBA2, and HBB in a single run was evaluated. The assay detects SNVs, and Indels and also uses two independent methods in parallel to detect CNVs. For the initial evaluation, 25 DNA samples with known genotypes, previously characterised in our lab, were used. For the validation study, 100 DNA samples were analysed using the NGS Thalassemia kit in parallel with the conventional molecular methods. The results obtained were assessed and compared. Results: The initial evaluation of the NGS thalassemia assay demonstrated the strength of the assay to accurately detect all variations in the analysed genes. Moreover, the assay also detected variations that were not previously identifiable by our conventional multi-method strategy, Thus, we demonstrated the ability of the assay for complete analysis of thalassaemia. The assay was successfully validated: the results obtained by the NGS assay were in complete concordance with results from parallel analysis by our standard strategy. Hence, the NGS Thalassemia kit was successfully implemented in our daily routine practice. Summary/conclusion: The implementation of the NGS Thalassemia kit allows for comprehensive analysis for the haemoglobinopathies in a single run. It is very efficient compared to our traditional previously conducted thalassemia testing, yielding results of unprecedented quality, as well as saving time on three levels - for the physician, for the lab, and most importantly for the patient. Reference 1. Kountouris, P., et al, Scientific reports, 2016.6: p. 26371.

Effect of HFE Gene Mutations on Iron Metabolism of Beta-Thalassemia Carriers

The human hemochromatosis protein HFE is encoded by the HFE gene and participates in iron regulation. The aim of this study was to detect the most frequent HFE gene mutations in a control population and in β-thalassemia trait (BTT) carriers, and to study their relationship with iron metabolism. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA2 quantification, iron (Fe), total Fe binding capacity and ferritin were assayed. HFE gene mutations were analyzed by real-time PCR. A total of 119 individuals (69 normal and 50 BTT) were examined. In the control group, 9% (6/69) presented a codon 282 heterozygous mutation (C282Y), and 19% a codon 63 mutation (H63D) (13/69, 11 heterozygotes and 2 homozygotes). In the BTT group, 3 carriers (6%) were heterozygous for C282Y, 14 (28%) for H63D, 1 (2%) for a codon 65 mutation and 1 (2%) was H63D and C282Y double heterozygous. Control group Fe metabolism did not show significant differences (p &gt; 0.05) according to whether or not they carried an HFE gene mutation; while the BTT group with and without HFE mutation showed higher Fe and ferritin than the control group (p &lt; 0.05). However, no increases in iron parameters were detected in BTT carriers that simultaneously exhibited an H63D mutation compared to BTT subjects without a mutation. Therefore, the iron metabolism alterations observed in BTT carriers could not be attributed to the presence of HFE gene mutations. It is likely that BTT individuals have other genetic modifiers that affect their iron balance.

Beta-Thalassemia Minor and SARS-CoV-2: Physiopathology, Prevalence, Severity, Morbidity, and Mortality

Background: Since the first year of the COVID-19 global pandemic, a hypothesis concerning the possible protection/immunity of beta-thalassemia carriers has remained in abeyance. Methods: Three databases (Pubmed Central, Scopus, and Google Scholar) were screened and checked in order to extract all studies about the incidence of confirmed COVID-19 cases, mortality rate, severity assessment, or ICU admission among patients with beta-thalassemia minor, were included in this analysis. The language was limited to English. Studies such as case reports, review studies, and studies that did not have complete data for calculating incidences were excluded. Results and discussion: a total of 3 studies out of 2265 were selected. According to our systematic-review meta-analysis, beta-thalassemia carriers could be less affected by COVID-19 than the general population [IRR = 0.9250 (0.5752; 1.4877)], affected by COVID-19 with a worst severity [OR = 1.5933 (0.4884; 5.1981)], less admissible into the ICU [IRR = 0.3620 (0.0025; 51.6821)], and more susceptible to die from COVID-19 or one of its consequences [IRR = 1.8542 (0.7819; 4.3970)]. However, all of those results remain insignificant with a bad p-value (respectively 0.7479, 0.4400, 0.6881, and 0.1610). Other large case-control or registry studies are needed to confirm these trends.

S Estimation of HbA2 Alone Sufficient for Screening Beta Thalassaemia Carriers: A Case in Perspective

Beta thalassaemia is one of the most common inherited haemoglobinopathies, characterised by reduced or absent production of the beta globin chain. In India, the carrier frequency of thalassaemia is estimated to be 3-4%. The prevention of Beta thalassaemia is the best strategy, and this can be achieved through carrier screening and prenatal diagnosis. Carriers of beta thalassaemia can be easily identified using haematological parameters such as complete blood count and High Performance Liquid Chromatography (HPLC) for haemoglobin analysis. The characteristic findings observed in thalassaemia carriers include microcytosis, hypochromia, with a Mean Corpuscular Volume (MCV) of less than 80 fL and Mean Corpuscular Haemoglobin (MCH) of less than 28 pg. They also present with elevated levels of HBA2 (α2δ2) ≥3.5%. Carrier screening for beta thalassaemia primarily relies on the observation of elevated HbA2 levels. However, in rare cases, some carriers can have normal HbA2 levels, leading to false-negative screening results. In a case involving a married couple who underwent routine preconceptional screening by complete blood count and HPLC for thalassaemia screening, the male partner had elevated HbA2 levels (5.2%), while the female partner had normal HbA2 levels (1.6%). Molecular testing revealed that the male partner was heterozygous for the Intervening Sequence (IVS) 1-5 (G&gt;C) mutation, while the female partner was found to be heterozygous for the CD41-42 (-CTTT) mutation. It is important to consider molecular testing of the HBB gene in couples, even if one partner is a carrier and the other partner has normal or borderline HbA2 levels.

Current Status of Thalassemia Minor Studies

Thalassemia minor carriage is one of the most common causes of anemia in Mediterranean countries. This study aimed to investigate the publications in scientific journals on thalassemia minor, which is an important health problem, especially in Mediterranean countries. The goal of this study was to retrieve data from journals that were indexed in the Web of Science (WoS; Thomson Reuters, New York, NY, USA) database. The WOS Core Collection was used to retrieve comprehensive bibliometric data. Keywords related to "beta-thalassemia carrier," or "beta-thalassemia trait," thalassemia minor" or "heterozygous beta-thalassemia" were used in a search query in the WOS search engine. The time frame was specified since 10 March 2022. The analysis included information on the increase of publications, the most active countries and institutions, the most cited journals, and the mapping of publications and keywords. A total of 8618 publications were retrieved. The first article was published in 1970, and the period between 1970 and 2021 was searched. The maximum number of publications was published in the year 2021. The number of publications had increased since 2009. Most of the publications were articles (61.696 %). The publications were from more than 100 disciplines and most of them were from Hematology (49.176%). The publications were from 274 different countries. Most of the publications were from the USA, Italy, and Greece. The USA is at the top of the list in the number of publications. But with active funding and support from the governments especially the Mediterranean countries, which have a higher prevalence of thalassemia minor, the productivity of scientific research should be increased.

Concordance Test of Various Erythrocyte Indices for Screening of Beta Thalassemia Carrier

Carrier screening for early detection of thalassemia in the general population needs a careful approach, especially in areas with limited health services. Various erythrocyte indices have been introduced as options for the first stage; however, the low-reliability value of these erythrocyte indices remains the problem. This study aimed to determine the most reliable index for screening beta-thalassemia carriers and distinguish it from iron deficiency anemia. A cross-sectional study was designed to explore thalassemia carrier status among medical students. Inter-rater reliability value of various indices was compared to Shine and Lal index. The Cohen's Kappa coefficient was calculated using SPSS v. 25.0. Among 320 respondents, 295 subjects were non-anemic and 25 were anemic subjects, whereas 105 subjects had low MCV and/or MCH values. Cohen's Kappa value showed moderate reliability results compared to Shine and Lal index for example Mentzer index (0.58), Ehsani index (0.57), Srivastava index (0.53), and Bordbar index (0.41), but showed very low-reliability results with Green and King index (0.04). New cut-off indices based on Kumar et al. were also compared, resulting in moderate reliability results. Since there was no Hb-electrophoresis test, the sensitivities and specificities of those indices could not be calculated. For this reason, a complete blood count can only be used for the early stages of screening for beta-thalassemia carriers, whereas Hb-electrophoresis and DNA tests were considered necessary to perform to confirm a diagnosis.