Hematopoietic Stem Cell Transplantation in Children with Sickle Cell Disease and Thalassemia Major: A National Database Study.

In patients with sickle cell disease (SCD) and beta-thalassemia major (TM), allogeneic hematopoietic stem cell transplantation (HSCT) was considered the only curative treatment option with a good survival rate. However, with the recent approval of gene therapies, more information is needed to understand the benefits and risks of these interventions. We performed a retrospective analysis of the Kids Inpatient Database to describe demographic features, short-term complications, and hospital charges of patients with SCD and TM treated with HSCT during 2006-2019 in the United States. The database was filtered using the International Classification of Diseases, 9th and 10th edition codes to identify children under 20 years of age with SCD or TM who underwent HSCT. A total of 513 children with SCD or TM who received HSCT were analyzed. The prevalence of HSCT per 1000,000 U.S. population increased from 0.31 in 2006 to 1.99 in 2019 (p < 0.001). The median age of children with SCD who underwent HSCT was 10 (6-15) years, and that for TM was 6 (3-11.5) years (p < 0.001). The combined mortality rate was 4% (2.4%-6.6%) but higher in the TM group. The length-of-stay and total charges were higher in the TM population (p < 0.01). This study provides national data on HSCT among hospitalized children with SCD and TM in the United States, demonstrating an increasing use of HSCT between 2006 and 2019. Although hospital mortality of HSCT in these conditions is low, it still represents a challenge, especially in TM patients.

Prevalence and Regional Distribution of Beta-Hemoglobin Variants in Saudi Arabia: Insights from the National Premarital Screening Program".

BACKGROUND: Hemoglobinopathies are among the most prevalent inherited disorders globally, with carrier prevalence varying significantly across regions. In Saudi Arabia, high rates of consanguineous marriages amplify the risk of these disorders. AIM: This study aims to assess the burden of hemoglobinopathies by evaluating the prevalence and regional distribution of beta-hemoglobin variants, including rare variants, among couples participating in the national premarital screening program. METHODS: Data were collected from the premarital genetic screening program and entered into the SEHA platform, covering the 13 administrative regions of Saudi Arabia. Blood samples underwent various screening tests for infectious and genetic diseases. Hemoglobin electrophoresis samples were analyzed using capillary electrophoresis, High-Performance Liquid Chromatography (HPLC), or a combination of both methods. RESULTS: From 2011 to 2018, 1,871,184 individuals were included in the study, with 49.8% male and 50.2% female. The average age was 30.2 years. Hemoglobin S (HbS) was identified in 88,431 individuals (4.7% of the tested population and 78.5% of abnormal screening results), primarily as a sickle cell trait. ß-thalassemia was the second most common disorder, identified in 22,420 individuals (1.2% of the population and 19.9% of hemoglobin disorders). HbC and HbD were each detected in 0.04% of cases, while HbO-Arab was identified in 0.007% and HbG in 0.006%. Hemoglobin E and hemoglobin Lepore were found to be extremely rare. CONCLUSION: The study demonstrates regional variation in the prevalence of hemoglobin genetic variants in Saudi Arabia. To effectively mitigate this risk, it is imperative to strengthen public education and awareness, particularly focusing on genetic screening and counseling.

Clinical burden and healthcare resource utilization associated with managing transfusion-dependent ß-thalassemia in France.

OBJECTIVE: To describe the clinical burden and healthcare resource utilization associated with managing transfusion-dependent ß-thalassemia (TDT) in France. METHODS: We used the French National Health Data System (système national des données de santé) to identify eligible patients from January 1, 2012, to March 1, 2019. Inclusion criteria were a diagnosis of ß-thalassemia, ≥8 red blood cell (RBC) transfusion episodes per year in ≥2 consecutive years following the diagnosis, and ≥1 year of follow-up data. Patients were excluded if medical records showed evidence of sickle cell disease, α-thalassemia, hereditary persistence of fetal hemoglobin, or hematopoietic stem cell transplant. Clinical complications, mortality, treatment use, and healthcare resource utilization were evaluated. RESULTS: Overall, 331 eligible patients with TDT were identified. Mean age was 26.1 (standard deviation [SD]: 18.0) years, and 50.5% were male. Common clinical complications were endocrine (26.0%), hepatobiliary (22.7%), and cardiopulmonary (18.7%). Fifteen (4.5%) patients died during follow-up, with a mortality rate of 1.16 deaths per 100 person-years (mean age of death: 52.5 years [SD: 22]). Patients had a mean of 13.5 (SD: 5.2) RBC transfusion episodes and 11.2 (SD: 5.3) iron chelation therapy treatments per year. Healthcare resource utilization was substantial, with a mean of 14.8 inpatient hospitalizations (including 13.8 mean inpatient day cases) and 16.9 outpatient prescriptions per patient per year. CONCLUSIONS: Patients with TDT in France experience significant clinical complications, elevated mortality, and substantial healthcare resource utilization driven by frequent RBC transfusion episodes and inpatient hospitalizations. These results reinforce the need for disease-modifying therapies for this patient population.

[Analysis of the Gene Mutation Type and Frequency of Thalassemia Patients in Jingzhou Area].

OBJECTIVE: To analyze the gene mutation types and frequence of thalassemia patients in Jingzhou area. METHODS: A total of 721 suspected thalassemia patients who were visited in Jingzhou Central Hospital from June 2019 to June 2022 were selected as the research objects. There were 204 males and 517 females. PCR-reverse dot hybridization method was used to analyze the types and frequencies of 23 common α or ß thalassemia gene mutations. RESULTS: Among the 721 patients with suspected thalassemia, 228 cases were positive for α or ß thalassemia gene, with a total positive rate of 31.62%, including 87 cases of α-thalassemia, accounting for 38.16%, and 140 cases of ß-thalassemia, accounting for 61.40%. There was 1 case of α ß complex thalassemia, accounting for 0.44%. A total of 4 types of α-thalassemia gene mutations were detected, all of which were deletion types, including αα/--SEA (64/87, 73.56%), αα/-α3.7 (14/87, 16.09%), --SEA /-α3.7 (7/87, 8.05%), αα/-α4.2 (2/87, 2.30%). Among 140 patients with ß-thalassemia, 138 were pure heterozygotes, and the genotypes of IVS-II-654M (63/140, 45.00%), CD41-42M (34/140, 24.29%), CD17M (18/140, 12.86%) and CD27-28M (10/140, 7.14%) accounted for 89.29% of all mutations (125/140), 2 cases of double heterozygosity (2/140, 1.43%) were found, no homozygous ß-thalassemia were detected; 1 case of αß complex thalassemia with genotype -α3.7/IVS-II-654M was found. The incidence of difference types of thalassemia was statistically significant (χ2=194.250, P < 0.001). The percentage of positive thalassemia genes was not significantly difference between male and female suspected patients (χ2=0.199, P =0.655). CONCLUSION: The α-thalassemia gene mutation in Jingzhou area is dominated by αα/--SEA, and the IVS-II-654M mutation is more common in ß-thalassemia, and α ß complex thalassemia is relatively rare, which can provide a reference for the formulation of prevention and treatment measures for thalassemia in Jingzhou area.

New Born Screening of Hemoglobinopathies in a Center Tunisian Population.

Sickle cell diseases, ß-thalassemia, and other hemoglobinopathies are common in Africa. Their distribution differs from one region to another. There are higher frequencies in Western and Northern Africa. Their clinical complications presented a real public health problem in each country. For this, early treatment can improve the severity of these diseases. Hemoglobinopathies targeted by screening are associated with SCD, ß, and α thalassemia. Our study aim is to report our experience with newborn screening for hemoglobinopathy in Tunis. The 156 newborn's cord blood was collected at the time of childbirth in the center region (Farhat Hached Hôspital). We opted for hemoglobin exploration to achieve maximum efficiency and effectiveness in screening. After that, all patients suspected to have hemoglobinopathies are affected by molecular investigation. Our findings showed the presence of some hemoglobinopathies such as ß-thalassemia and α-thalassemia with the following frequencies: 12% and 0.33%. The molecular results show the presence of HBB: c.93-21G>A, IVS-I-110G>A, HBBc. -106G>A -56G>C, HBBc.404T>C, Hb Yaounde described for the first time in Tunisia and α 3,7 . In conclusion, newborn screening diagnoses neonates with different examples of hemoglobinopathies, which will be beneficial not only for the care of the child but also for genetic counseling of the potential risk's parents.

Growth and endocrinopathies among children with ß-Thalassemia major treated at Dubai Thalassemia centre.

BACKGROUND: ß-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This in turn leads to multiple organ damage and endocrinopathies. This study aims to assess the prevalence of growth retardation, hypothyroidism, and diabetes mellitus in children and adolescents with BTM treated at Dubai Thalassemia Centre. METHODS: A total of 105 children and adolescents were included in this retrospective observational study. RESULTS: 39 children and 66 adolescents' data were analyzed. Females composed 51.3% (n = 20) of children and 53.0% (n = 35) of adolescents. Pretransfusion hemoglobin below 9 gm/dl was observed in 10.8% (n = 4) and 10.6% (n = 7) in children and adolescents, respectively. The mean age of menarche was 13.5 years. Among all study participants, 22.6% (n = 14) had normal height velocity whereas 37.1% (n = 23) had reduced height velocity in one year and 40.3% (n = 25) had reduced height velocity in two consecutive years. The proportion of children and adolescents showing reduced height velocity was significantly higher in females compared to the males (90.6% versus 63.3%, respectively, Chi-square = 6.597, p-value = 0.010). Although none of the study participants had diabetes mellitus, 26.1% (n = 12/46) had pre-diabetes. Elevated TSH was observed in 14.7% (n = 5) children and 8.1% (n = 5) adolescents while low FT4 was reported in one child and one adolescent. CONCLUSION: Of all endocrinopathies seen among children and adolescents with BTM, growth delay remains the main concern for this group of patients. Effective treatment is key to further reducing endocrinopathies. Although the sample size is limited, we postulate that the low percentage of endocrinopathies among children with BTM treated at Dubai thalassemia center and the low level of pretransfusion anemia reflect the effective transfusion and chelation at the center.

Premarital Screening is Pivotal in Reducing the Births of Babies Affected with Thalassemia Major in Iraq.

Thalassemia major is one of the health problems in Iraq, especially in Kurdistan. Pre-marriage mandatory preventive screening program was established in Kurdistan in 2008, which allowed us to study the prevalence of different hemoglobinopathies among newly married young adults in this region. A total of 1154 subjects (577 couples) attending the Koya district, premarital Health center, were screened using red cell indices. Those who had mean corpuscular volume (MCV)<80 fl and mean corpuscular hemoglobin (MCH)<27 pg had high-performance liquid chromatography and iron studies. Out of 1154 individuals that were evaluated, 183 (11.9%) had low MCV and MCH. Of the former 183 subjects, 69 (5.97%) had ß-thalassemia trait, 10 (0.86%) had δß-thalassemia trait, and no other hemoglobinopathies were recorded in our study. There was second-degree consanguinity in 4.7% of all 577 couples. In two couples, both partners had ß-thalassemia trait and both were consanguineous. Both couples decided to separate after counseling. Based on the current study, the role of the premarital screening program in decreasing the number of new thalassemia major cases among the Kurdish population is laudable. Therefore, mandatory premarital screening is advised in all parts of Iraq.

Survival and causes of death in patients with alpha and beta-thalassemia in Northern Thailand.

BACKGROUND: Thalassemia is the most prevalent hereditary anaemia worldwide. Severe forms of thalassemia can lead to reduced life expectancy due to disease-related complications. OBJECTIVES: To investigate the survival of thalassemia patients across varying disease severity, causes of death and related clinical factors. PATIENTS AND METHODS: We conducted a retrospective review of thalassemia patients who received medical care at Chiang Mai University Hospital. The analysis focused on survival outcomes, and potential associations between clinical factors and patient survival. RESULTS: A total of 789 patients were included in our study cohort. Among them, 38.1% had Hb H disease, 35.4% had Hb E/beta-thalassemia and 26.5% had beta-thalassemia major. Half of the patients (50.1%) required regular transfusions. Sixty-five patients (8.2%) had deceased. The predominant causes of mortality were infection-related (36.9%) and cardiac complications (27.7%). Transfusion-dependent thalassemia (TDT) (adjusted HR 3.68, 95% CI 1.39-9.72, p = 0.008) and a mean serum ferritin level ≥3000 ng/mL (adjusted HR 4.18, 95% CI 2.20-7.92, p < 0.001) were independently associated with poorer survival. CONCLUSIONS: Our study highlights the primary contributors to mortality in patients with thalassemia as infection-related issues and cardiac complications. It also underscores the significant impact of TDT and elevated serum ferritin levels on the survival of thalassemia patients.

Spanish registry of hemoglobinopathies and rare anemias (REHem-AR): demographics, complications, and management of patients with ß-thalassemia.

INTRODUCTION: The increase in the number of patients with hemoglobinopathies in Europe in recent decades highlights the need for more detailed epidemiological information in Spain. To fulfil this need, the Spanish Society of Pediatric Hematology and Oncology (SEHOP) sponsored the creation of a national registry of hemoglobinopathies known as REHem-AR (Spanish Registry of Hemoglobinopathies and Rare Anemias). Data from the transfusion-dependent (TDT) and non-transfusion-dependent (NTDT) ß-thalassemia cohorts are described and analyzed. METHODS: We performed an observational, multicenter, and ambispective study, which included patients of any age with TDT and NTDT, registered up to December 31, 2021. RESULTS: Among the 1741 patients included, 168 cases of thalassemia were identified (103 TDT and 65 NTDT-patients). Survival at 18 years was 93% for TDT and 100% for NTDT. Regarding management, 80 patients with TDT (77.7%) and 23 patients with NTDT (35.4%) started chelation treatment during follow-up, with deferasirox being the most widely used. A total of 76 patients within the TDT cohort presented at least 1 complication (73.8%), the most frequent being hemosiderosis and osteopenia-osteoporosis. Comparison of both cohorts revealed significant differences in the diagnosis of hepatic hemosiderosis (p = 0.00024), although these were not observed in the case of cardiac iron overload (p = 0.27). DISCUSSION: Our registry enabled us to describe the management of ß thalassemia in Spain and to analyze the morbidity and mortality of the cohorts of patients with TDT and NTDT. Complications related to iron overload in TDT and NTDT account for most of the morbidity and mortality of the disease, which is associated with a considerable social, psychological, and economic impact, although cardiac, osteopathy and endocrinological complications requiring more attention. The convenience and simplicity of online registries make it possible to homogenize variables and periodically update data, thus providing valuable information on these diseases.

Molecular Characterization of α- and ß-Thalassemia Among Children Less Than 18 Years Old in Guizhou, China.

BACKGROUND: Thalassemia is an inherited hemolytic disease, the complications and sequelae of which have posed a huge impact on both patients and society. But limited studies have investigated the molecular characterization of α- and ß-thalassemia in children from Guizhou, China. METHODS: Between January 2019 and December 2022, a total of 3301 children, aged 6 months to 18 years, suspected of having thalassemia underwent molecular analysis. RESULTS: Out of the total sample, 824 (25%) children were found to carry thalassemia mutations. The carrier rates of α-thalassemia, ß-thalassemia, and α + ß-thalassemia were determined as 8.1%, 15.6%, and 1.3%, respectively. Approximately 96.5% of the α-thalassemia gene mutations were --SEA (51%), ααCS (20.9%), -α3.7 (19.6%), and -α4.2 (5.0%). The most prevalent mutations of ß-thalassemia were ßCD17(A>T) (41.5%), ßCD41-42(-TTCT) (37.7%), and ßIVS-II-654(C>T) (11.3%). Additionally, we identified rare cases, including one case with ααHb Nunobiki/αα, two cases with triplicated α-thalassemia (one case with ααα/ααα and ßCD41-42/ßN and the other with ααα-3.7/αα and ßE CD26/ßN), and also one case with α Q-Thailandα/-α4.2 and ßCD41-42/ßN. CONCLUSIONS: Our study findings provide important insights into the heterogeneity of thalassemia carrier rates and molecular profiles among children in the Guizhou region. The findings support the development of prevention strategies to reduce the incidence of severe thalassemia in the future.

[Health status and quality of life in ß-thalassemia adults in Marseille, France]. / État de santé et qualité de vie des patients ß-thalassémiques adultes à Marseille, France.

INTRODUCTION: The life expectancy of ß-thalassemia patients has increased over the last 20 years. In this study, we evaluated the current health status and quality of life of these patients managed in a reference center in Marseille. METHODS: This is a single-center, descriptive study conducted between June and August 2019 in patients over 18 years of age with ß-thalassemia major or intermedia. Clinical and paraclinical data were collected retrospectively and the SF-36 health survey questionnaire was proposed to each patient. RESULTS: 43 of 64 selected patients were included and divided into 2 groups: 35 patients with transfusion-dependent ß-thalassemia and 8 patients with non-transfusion-dependent ß-thalassemia. Liver iron overload is the most frequent complication, present in 80% of transfusion-dependent and 62.5% of non-transfusion-dependent patients. Cardiac iron overload is present only in the transfusion dependent ß-thalassemia group (20%). Hypogonadotropic hypogonadism remains the most common endocrine disorder (41.9%) followed by osteoporosis (37.2%). Among the 31 patients who completed the SF-36 questionnaire, physical and mental quality of life scores were lowered in transfusion dependent (respectively 42.7 and 46.8) as in non-transfusion-dependent patients (respectively 43.8 and 28.9). CONCLUSION: Despite an improvement in medical care, our patients with ß-thalassemia show an alteration in their quality of life that will need to be characterized in the entire French cohort.

Prevalence of thalassemia-carrier couples and fertility risk assessment.

Thalassemia is a highly prevalent hematologic disease in Guizhou, China. This study aimed to determine the epidemiological characteristics of thalassemia in couples at childbearing age and assess the neonatal risk of thalassemia in this subpopulation. A cohort of 4481 couples at childbearing age were recruited for thalassemia carrier screening by both traditional hematological tests and next-generation sequencing. Of them, 1314 (14.66%) thalassemia carriers were identified, including 857 (9.76%) α-thalassemia, 391 (4.36%) ß-thalassemia, and 48 (0.54%) composite α and ß-thalassemia. A total of 12 α-globin gene alterations and 16 ß-globin mutations were detected, including four novel thalassemia mutations. SEA was the most common α-thalassemia genotype (26.86%), CD41-42 the most common ß-thalassemia genotype (36.57%), and αα/- α3.7 + CD41-42 the most common composite α- and ß-thalassemia genotype (18.75%). Ethnically, the Zhuang had the highest rate of thalassemia gene carriers among the ethnic groups. Geographically, Qiannan had the highest rate of thalassemia gene carriers. In addition, 38 of the 48 couples with composite α- and ß-thalassemia were high-risk thalassemia carriers, and 4 carrying the -SEA/αα gene needed fertility guidance.

Point-of-Care Diagnostic Test for Beta-Thalassemia.

Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world population. Among various Hb disorders, approximately 1.5% of the world population carries ß-thalassemia (ß-Thal), affecting 40,000 newborns every year. Early screening and a timely diagnosis are essential for ß-thalassemia patients for the prevention and management of later clinical complications. However, in Africa, Southern Europe, the Middle East, and Southeast Asia, where ß-thalassemia is most prevalent, the diagnosis and screening for ß-thalassemia are still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, which is a paper-based microchip electrophoresis platform that enables the first point-of-care diagnostic test for ß-thalassemia. We evaluated the accuracy of Gazelle for the ß-Thal screening across 372 subjects in the age range of 4-63 years at Apple Diagnostics lab in Mumbai, India. Additionally, 30 blood samples were prepared to mimic ß-Thal intermediate and ß-Thal major samples. Gazelle-detected levels of Hb A, Hb F, and Hb A2 demonstrated high levels of correlation with the results reported through laboratory gold standard high-performance liquid chromatography (HPLC), yielding a Pearson correlation coefficient = 0.99. This ability to obtain rapid and accurate results suggests that Gazelle may be suitable for the large-scale screening and diagnosis of ß-Thal.

Impacts of ß-thalassemia/hemoglobin E disease on pregnancy outcomes.

OBJECTIVE: To compare obstetric outcomes between women with ß-thalassemia/hemoglobin E (ß-thal/HbE) disease and those of low-risk pregnancies, and also between the two subgroups, ß-thal0/HbE and ß-thal+/HbE disease. METHODS: A retrospective cohort study was undertaken on pregnant women with ß-thal/HbE disease and low-risk pregnancies, which were randomly selected with a case-to-control ratio of 1:10. RESULTS: Pregnancies with ß-thal/HbE disease were identified in 0.19% of 59 152 pregnancies, including 104 women in the study group and 1040 women in the control group. The mean gestational age and mean birth weight were significantly lower in the study group. The prevalence of fetal growth restriction, preterm birth and low birth weight were significantly increased in the study group based on both univariate and multivariate analysis. The impacts were more striking in the ß-thal0/HbE subgroup than in the ß-thal+/HbE subgroup. The cesarean rate was significantly higher in the study group. No maternal death or serious complication was found in this cohort. CONCLUSION: Based on this cohort, the largest ever published, ß-thal/HbE disease is significantly associated with increased incidence of fetal growth restriction, preterm birth and low birth weight. The impacts were more pronounced in the ß-thal0/HbE subgroup. Pregnancy may be relatively safer for women with ß-thal/HbE disease.

ß-Thalassemia and Diabetes Mellitus: Current State and Future Directions.

ß-Thalassemia major is a congenital hemoglobin disorder that requires regular blood transfusion. The disease is often associated with iron overload and diabetes mellitus, among other complications. Pancreatic iron overload in ß-thalassemia patients disrupts ß-cell function and insulin secretion and induces insulin resistance. Several risk factors, including family history of diabetes, sedentary lifestyle, obesity, gender, and advanced age increase the risk of diabetes in ß-thalassemia patients. Precautionary measures such as blood glucose monitoring, anti-diabetic medications, and healthy living in ß-thalassemia patients notwithstanding, the prevalence of diabetes in ß-thalassemia patients continues to rise. This review aims to address the relationship between ß-thalassemia and diabetes in an attempt to understand how the pathology and management of ß-thalassemia precipitate diabetes mellitus. The possible employment of surrogate biomarkers for early prediction and intervention is discussed. More work is still needed to better understand the molecular mechanism(s) underlying the link between ß-thalassemia and diabetes and to identify novel prognostic and therapeutic targets.

Spectrum of Adrenal Dysfunction in Hemoglobin E/Beta Thalassemia.

BACKGROUND: Adrenal insufficiency (AI) in hemoglobin E (HbE)/beta thalassemia, including evaluation of mineralocorticoid axis, had not been studied. AIMS AND OBJECTIVES: In this study, we attempted to evaluate the prevalence of AI in HbE/beta thalassemia and wanted to determine if the prevalence of AI varied according to severity of HbE/beta thalassemia and transfusion requirements. METHODS: In this observational, cross-sectional study, 104 patients with HbE/beta thalassemia were evaluated. Among them, 57 and 47 were transfusion dependent and non-transfusion dependent. According to Mahidol criteria, patients were classified into mild (n = 39), moderate (n = 39), and severe (n = 26) disease. Early morning (8 Am) serum cortisol, plasma ACTH, and plasma aldosterone, renin were measured. Patients with baseline cortisol of 5 to 18 µg/dL underwent both 1 µg and 250 µg short Synacthen test. According to these results, patients were classified as having either normal, subclinical, or overt (primary/secondary) adrenal dysfunction. RESULTS: Adrenal insufficiency was found in 41% (n = 43). Among them 83.7% (n = 34) had primary AI and 16.3% (n = 9) had secondary AI. Thirty-three patients (31%) with normal or elevated ACTH and with low or normal aldosterone with high renin were diagnosed as having subclinical AI. There was no difference in prevalence of AI between transfusion dependent and non-transfusion dependent (P = .56) nor was there was any difference in prevalence of AI according to disease severity (P = .52). CONCLUSION: Adrenal insufficiency is common in HbE/beta thalassemia and is independent of transfusion dependency and disease severity.

Global distribution of ß-thalassemia mutations: An update.

One excellent illustration of how a single gene abnormality may result in a spectrum of disease incidence is the incredible phenotypic variety of ß-thalassemia, which spans from severe anemia and transfusion needs to an utterly asymptomatic sickness. However, genetic causes of ß-thalassemia and how the anemia's severity might be altered at various stages in its pathophysiology have been well investigated. There are currently known to be more than 350 mutations that cause genetic disease. However only 20 ß thalassemia mutations account for more than 80% of the ß thalassemia mutation across the globe due to phenomenon of geographical clustering where each population has a few common mutations together with a varying number of rare ones. Due to migration of the population, the spectrum of thalassemia mutation in changing from time to time. In this review, efforts are made to collate ß globin gene mutations in different countries and populations.

Effects on hearing after long-term use of iron chelators in beta-thalassemia: Over twenty years of longitudinal follow-up.

OBJECTIVE: The role of iron chelation in causing hearing loss (HL) is still unclear. The present study assessed the prevalence of HL among transfusion-dependent thalassemia (TDT) patients who underwent audiological follow-up over a 20-year period. METHODS: We retrospectively analyzed clinical records and audiological tests from January 1990 (T0) to December 2022 (T22) of a group of TDT patients who received iron chelation therapy with deferoxamine (DFO), deferiprone (DFP) or deferasirox (DFX), in monotherapy or as part of combination therapy. RESULTS: A total of 42 adult TDT patients (18 male, 24 female; age range: 41-55 years; mean age: 49.2 ± 3.7 years) were included in the study. At the T22 assessment, the overall prevalence of sensorineural HL was 23.8 % (10/42). When patients were stratified into two groups, with and without ototoxicity, no differences were observed for sex, age, BMI, creatinine level, pre-transfusional hemoglobin, start of transfusions, cardiac or hepatic T2 MRI; only ferritin serum values and duration of chelation were significantly higher (p = 0.02 and p = 0.01, respectively) in patients with hearing impairment in comparison to those with normal hearing. CONCLUSION: This study with long-term follow-up suggests that iron chelation therapy might induce ototoxicity; therefore, a long and accurate audiological follow-up should be performed in TDT patients.

Carrier rate of thalassemia among 25,910 high school students in Shaoguan area, China.

OBJECTIVES: As one of the most common hereditary diseases, thalassemia affects a large number of people in China. The aim of this study was to investigate the feasibility of a method based on next-generation sequencing (NGS) for screening of thalassemia carriers among high school students in the Shaoguan area. MATERIALS AND METHODS: The NGS-based method was performed using 25,910 high school students recruited from 38 schools. The screening yield was systematically analyzed. Before screening, a lecture on how the disease is inherited, the symptoms of thalassemia, and how to prevent it was given to 28,780 students. RESULTS: Implying successful delivery of information on the disease, 90.03% (25,910 of 28,780) of the students agreed to join this program for thalassemia screening. A thalassemia carrier rate of 15.99% (4144 of 25,910) was found. Also, 69 rare genotypes (28 of α-thalassemia and 41 of ß-thalassemia) and 9 novel variants were identified. CONCLUSIONS: This NGS-based method provided a feasible platform for high school population thalassemia screening. Combined with a clinical follow-up strategy, it could help eventually to prevent the births of affected children.

COVID-19 and ß-thalassemia: in lieu of evidence and vague nexus.

Coronavirus disease 19 (COVID-19) is an infectious disease caused by severe acute respiratory coronavirus 2 (SARS-CoV-2) causing acute systemic disorders and multi-organ damage. ß-thalassemia (ß-T) is an autosomal recessive disorder leading to the development of anemia. ß-T may lead to complications such as immunological disorders, iron overload, oxidative stress, and endocrinopathy. ß-T and associated complications may increase the risk of SARS-CoV-2, as inflammatory disturbances and oxidative stress disorders are linked with COVID-19. Therefore, the objective of the present review was to elucidate the potential link between ß-T and COVID-19 regarding the underlying comorbidities. The present review showed that most of the ß-T patients with COVID-19 revealed mild to moderate clinical features, and ß-T may not be linked with Covid-19 severity. Though patients with transfusion-dependent ß-T (TDT) develop less COVID-19 severity compared to non-transfusion-depend ß-T(NTDT), preclinical and clinical studies are recommended in this regard.