Lived experiences of adolescents with thalassemia major: A phenomenological study/ lived experiences in tm adolescents.

Aim and objective: To find out the proportion of transfusion reaction symptoms of beta-thalassemia in paediatric age group patients and to estimate the biochemical parameters of liver functions and correlate them with serum ferritin levels. Material and method: The present cross-sectional study was conducted on 120 children with known beta thalassemia aged between 2-12 years on repeated blood transfusion. A thorough clinical examination with particular importance on the presence of pallor, jaundice, and signs of thalassemic features was done. An abdominal examination was done to rule out hepatosplenomegaly. Blood samples were collected for appropriate investigations including serum ferritin level, transferrin saturation, and liver function test. Results: In this study, 27.5% and 72.5% of children belonged to the 2-5 years and 6-12 years age category respectively. The majority of study subjects were male (65.33%). The incidence of jaundice, ascites, and hepatomegaly was found to be 90.83%, 36.67%, and 100% respectively. The incidence of jaundice, ascites, and hepatomegaly are more common in older age children. A significant positive correlation was found between serum ferritin and total bilirubin, direct bilirubin, and SGPT (P<0.05). Conclusion: In the present study, there was a positive significant correlation between serum ferritin and total bilirubin, direct bilirubin, and SGPT. Thus, as serum ferritin increases there is an increase in liver function parameters and enzymes and there will be more derangement in liver function probably because of an iron overload condition.

Background/Objectives: Factors modulating phenotypic variability in Rett syndrome (RTT, OMIM 312750) include X chromosome inactivation (XCI), type of MECP2 variant, and/or disease modifiers. Emerging evidence also points to multi-locus genetic variants. Understanding the phenotypic variability associated with multi-locus genetic diagnoses in individuals with RTT and MECP2-related disorders would be important not only for accurate diagnosis, risk stratification and clinical management but also to explain symptoms that might not be typically associated with RTT. Methods: We present a case series of five individuals with a diagnosis of RTT or an MECP2-related disorder with co-occurring genetic findings, including pathogenic variants, variants of unknown significance and chromosome duplications. Clinical features such as neurodevelopmental history and comorbid medical conditions were assessed alongside the genetic findings. Results: A review of 200 cases with RTT identified five cases (all females aged 7–27 years) with a co-occurring genetic finding. Each case harboured at least one additional genetic variant that included a beta thalassaemia trait, Calmodulin 3 (CALM3) missense variant, maternally inherited 22q12.3 to q13.1 duplication, 7p14.3 and Dynein Cytoplasmic 1 Heavy Chain 1 (DYNC1H1) variants of uncertain significance and a pathogenic Set Domain-containing protein 5 (SETD5) variant. A rare triple genetic finding was illustrated in a single case, combining MECP2, CALM3, and DYNC1H1 variants. Conclusions: This case series supports the premise that RTT and MECP2-related disorders exist in a more complex neurogenetic spectrum than previously defined. It also emphasises the complexity within MECP2-related disorders. They are not static, and in the context of severe treatment resistant epilepsy, MECP2 disorders can evolve over time, necessitating diagnostic reclassification. Although the co-occurrence of multiple genetic disorders in RTT and MECP2-related disorders is rare, these cases underscore the importance of considering cumulative genetic burden when evaluating individuals with atypical features or evolving neurodevelopmental phenotypes.

Behind the splenomegaly: a parasitic twist in siblings with beta thalassemia trait.

Detection of Neurological Complications in Egyptian Children with Beta Thalassemia : A single-center cross-sectional study

Background: Sickle cell gene is common in various population groups in different parts of India. This makes sickle cell disease a common and clinically relevant symptomatic hemoglobinopathy in India. Clinical features of this disease are very variable. The current review with perspective was created by reviewing national and international literature. Materials and Methods: Literature search in PubMed and in Indian literature resources as well as the author’s own experience of this disease biology spanning over more than 35 years was used as the primary database. Sickle cell anemia, sickle cell disease, was used as the stem against the search terminologies such as Clinical heterogeneity, Population distribution in India, Molecular Mechanisms for severity, Mechanisms, and Blood transfusion. Original articles and review articles were given preference over individual case reports. Results: There were many studies on the relative prevalence of the disease in different parts of the country. The disease in general was milder compared to the Afro-Caribbean form of the disease. The disease in Nagpur and adjoining areas was more severe than that in Gujarat and adjoining Maharashtra. The sickle cell disease in the north east tea garden workers was also milder as also the disease seen in the Nilgiri hills of Tamil Nadu and Waynad district of Kerala. The clinical features looked into for severity are painful crisis, chest syndrome, necrosis of femoral heads, and stroke. Little data are available on the perinatal complications of the disease. The frequency and severity of the disease with the above-mentioned clinical presentations were lower in milder forms of disease and presented in relatively older age groups. High fetal hemoglobin and a deletional variety of alpha thal-mutation was associated with milder forms of the disease. Nutritional deficiency, degree of anemia, and coinheritance of beta thalassemia gene tend to minimize the severity. Splenomegaly was very common and often HbS beta thalassemia is misdiagnosed as sickle cell anemia. There are many ways by which the clinical presentation of Sickle cell disease (SCD) is seen but broadly interplay of vaso occlusion and hemolysis in different degrees and in different anatomical locations determines the clinical features and presentation of the condition. High ambient temperature and bad weather conditions also contribute toward differential clinical presentation of the disease and obviously occupation also plays a role. Priapism, pedal ulcers, and ocular manifestations of SCD are rarely reported. Conclusion: There is general consensus that there is clinical heterogeneity in the presentation of sickle cell disease in India both within and across population groups due to genetic and environmental background of the population. However, there are huge gaps in clinical information in this disease in different areas of the country and there are needs to initiate a large-scale population study related to clinical heterogeneity of the disease and correlate these presentations with genetic and environmental as well as nutritional status of the population. Most of the clinical presentation papers are often from hospital data and surely present more severely affected population. Chronic cardiovascular, renal, pulmonary, and hepatic conditions in various groups and in different age groups are poorly recorded.

Objectives: The objective of the study is to describe the distribution of hemoglobin (Hb) variants among patients referred for high-performance liquid chromatography (HPLC) screening at a tertiary care center in India. Hemoglobinopathies are among the most common inherited disorders in India. While population-based studies provide prevalence estimates, hospital-based data offer insights into the clinical burden in high-risk groups. This study presents a descriptive analysis of Hb variants among patients referred for HPLC testing at a tertiary referral center. Material and Methods: This retrospective study analyzed 3,052 patients referred for HPLC screening between October 2019 and October 2024. Patients were referred based on clinical suspicion of anemia or hemoglobinopathy. Hb variants were identified using HPLC, and demographic and laboratory data were retrieved from electronic medical records. Results: Abnormal Hb patterns were observed in 48.53% of referred patients. Beta thalassemia trait (36.39%) and HbE variants (Homozygous: 20.66%, Heterozygous: 14.44%) were most common, with regional clustering in West Bengal and Assam. Sickle cell variants were more prevalent in Odisha, Jharkhand, and Telangana. Conclusion: This referral center-based analysis highlights the regional burden of hemoglobinopathies and underscores the need for targeted screening and genetic counseling. Findings should be interpreted in the context of referral bias and the absence of confirmatory molecular testing.

Introduction Indonesia is located along the “Thalassemia Belt,” a hotspot region for hemoglobinopathies, including beta thalassemia, with approximately 3–10% of the Indonesian population diagnosed with this disease. Thalassemia was diagnosed using the Hb analysis results. However, the single nucleotide variant (SNVs) database for the Indonesian population, which leads to β-thalassemia disease, has not been extensively studied. This study aimed to profile the genetic variations in Indonesian β-thalassemia patients and conduct in silico characterization of their functional effects. Methods Twenty thalassemia patients were recruited for this study. The sample collected from the respondents was whole blood in EDTA tubes, with a minimum collection time of 14 days after blood transfusion. Genomic DNA (gDNA) was extracted using a commercial kit, directly amplified using Polymerase Chain Reaction (PCR) with specific primers for β-globin and sequenced using Sanger Sequencing. All variants located in exon regions were analyzed using FinchTV, BioEdit, and Biovia Discovery Studio to determine their functional impact. Results Ten reported pathogenic variants were observed along with one rare variant. Genetic variations found according to its common name and nomenclature based on Human Genome Variation Society (HGVS) are IVS1nt.1 (HGVS: c.92+1G>A), IVS1nt.1 (HGVS: c.92+1G>T), IVS1nt.2 (HGVS: c.92+2G>T), IVS1nt.5 (HGVS: c.92+5G>C), IVS2nt.654 (HGVS: c.316-197C>T), Cd15 (HGVS: c.47G>A), Cd26 (HGVS: c.79G>A), Cd30 (HGVS: c.92G>C), Cd41/42 (c.126_129delCTTT), and Cd35 (HGVS: c.110delC). Analysis of amino acid interactions revealed that disease-causing mutations were clinically relevant in each subject. Conclusions This study has bioinformatically proven the effect of genetic mutations and predicted their effect on amino acid interactions. These findings contribute to the study of Indonesian thalassemia and require further research.

This study aimed to evaluate patients with beta thalassaemia major using the cardiac electrophysiological index of balance, a new electrocardiography parameter, and to predict ventricular arrhythmias. In this study, 60 beta thalassaemia major and 60 healthy children were included. All patients were evaluated with echocardiography. P-wave dispersion, repolarisation times, repolarisation dispersion times, and cardiac electrophysiological balance index were measured using 12-lead electrocardiography. Heart rate variability parameters were evaluated with a 24-hour Holter electrocardiography. Left ventricular functions were similar between the groups. Although repolarisation times (QT, JT, and JTp) were significantly lower in the beta thalassaemia major group, heart rate-corrected repolarisation times were similar. Except for Tpe/QT, which is one of the repolarisation dispersion parameters, the other parameters were similar. The heart rate-corrected cardiac electrophysiological index of balance ratio was significantly higher in the beta thalassaemia major group. QRS duration and QRS-dispersion duration (QRS-d) were similar between the groups. There was a correlation between blood ferritin levels and LVmass-i, Tpe/QT, Tpe/QTc, QTc/QRS ratio, and QT, JT, and JTp values. Patients with beta thalassaemia major are at high risk for ventricular arrhythmia due to a high QTc/QRS ratio, despite normal left ventricular systolic, diastolic, and autonomic function in the early period. We believe that there is a moderate correlation between blood ferritin levels and the QTc/QRS ratio and that the QTc/QRS ratio can provide important information for the follow-up and evaluation of patients with beta thalassaemia major. Despite normal early ventricular function in the beta thalassaemia major group, they were at high risk of ventricular arrhythmias.

Performance of complete blood count indices in differentiating between iron deficiency anemia and beta thalassemia trait in Egyptian children

Heterogeneous Autoimmune Complications Following Non-TBI Allogeneic Hematopoietic Stem Cell Transplantation: A Single-Center Report on Pediatric Patients with Major Thalassemia

Distinctive expression of circulating miR-22-3p and BCL11a as molecular markers of beta thalassemia

Spinal cord compression secondary to extramedullary hematopoiesis in beta thalassemia major

Abstract Background Beta thalassemia is an autosomal recessive disorder characterised by reduced synthesis of beta globin chains. Magnetic resonance T2* is considered the gold standard to assess cardiac iron overload and to guide iron chelation. However, some patients still present higher incidence of cardiovascular events, despite normal T2* levels. This discrepancy suggests that we might need additional parameters to identify those patients at higher risk of future events. Purpose this study aimed to assess differences in speckle tracking echocardiography (STE) parameters between transfusion dependent β-thalassemia (TDβT) patients with and without CV disease. Methods "Atrial fibrillation in β-thalassemia" is a prospective, single-center, observational study aimed at identifying the clinical, electrocardiographic and imaging features of TDβT patients. For the present cross-sectional study, global longitudinal strain (GLS), peak atrial longitudinal strain (PALS) and myocardial work (MW) were performed. The primary endpoint was the difference in STE indices between TDβT patients with and without CV disease (defined as heart failure, stroke or atherosclerotic vascular disease). The association between STE indices and CV disease was calculated using uni- and multi-variated logistic regression models. Receiver-operating characteristics (ROC) curves were constructed to identify STE parameters that could have a stronger association with CV disease and the best cut-off points for those parameters. Results between August 2022 and January 2025, 228 patients with TDβT were enrolled. Among them, 17 had a previous cardiovascular event. Patients with CV disease had higher prevalence of arterial hypertension (29% vs 9%, p-value 0.006) and atrial fibrillation (35% vs 12%, p-value 0.007). No differences were found in CMR parameters. Patients with CV disease had lower values of GLS (-19% vs -21%, p-value 0.009), PALS (25% vs 35% p-value 0.003), global constructive work (GCW - 1870 mmHg% vs 2185 mmHg%, p-value 0.004) and global work index (GWI - 1690 mmHg% vs 1952 mmHg%, p-value 0.01). ROC curve analysis revealed good diagnostic accuracy of STE indices in identify patients with CV disease and different empirical cut-off values were established for each parameter (best cut-off points: GLS -19.65%, PALS 37.1%, GWI 1966.5 mmHg%, GCW 2161 mmHg%). The highest diagnostic accuracy was achieved combining all STE indices together (sensitivity of 93%, specificity of 55%, AUC 0.77). After multivariate logistic regression analysis, GLS < -19.65% (OR 3.29, 95%, CI 1.07-10.06, p-value 0.03), GWI (OR 0.99, 95% CI 0.996-0.999, p value 0.01), GCW (OR 0.99, 95% CI 0.996-0.999, p-value 0,007) and PALS (OR 0.95, 95% CI 0.90-0.99, p-value 0.04) were found to be independently associated with the presence of CV events. Conclusions in TDβ-thalassemia, patients with CV had lower values of GLS, MW and PALS. The best diagnostic accuracy was achieved combing together all STE parameters.

Background: Thalassemia major (TM) is a chronic hereditary blood disorder requiring lifelong transfusions and chelation therapy, imposing a substantial physical, psychological, social, and financial burden on caregivers. Assessing caregivers’ quality of life (QoL) and coping strategies is essential to understanding their adaptive functioning and identifying areas requiring psychosocial support. To evaluate the quality of life and coping strategies among caregivers of children with thalassemia major attending a tertiary care hospital in Southern Rajasthan. Methods: A cross-sectional study among 140 caregivers of children with thalassemia major used a structured questionnaire with sociodemographic data, WHOQOL-BREF, and brief COPE. Data were analyzed using descriptive statistics, chi-square, and ANOVA, with p<0.05 as the significance level. Results: Most caregivers were male (65.7%), rural residents (80.7%), and belonged to lower socioeconomic strata (70.7%). Emotional support (85.71%), religious coping (84.29%), and informational support (82.14%) were the most frequently adopted strategies. Social relationships showed the highest QoL scores (mean 10.46±2.22), while psychological health was the most affected domain (mean 16.61±3.62). Gender and education were significantly associated with QoL across multiple domains (p<0.05), whereas duration of illness and age showed no significant association. Conclusion: Caregivers of children with thalassemia major experience considerable psychosocial strain, particularly affecting psychological and environmental well-being. Adaptive coping strategies, especially emotional and religious coping, appear to support resilience.

Chronic myeloid leukemia (CML) is rare in children and extremely uncommon in patients with underlying hemoglobinopathies such as beta thalassemia. This report describes a 12‑year‑old beta thalassemia patient, who presented with fever, pallor and weakness, and was found to have marked hepatosplenomegaly and leukocytosis. Peripheral blood showed leukocytosis with increased myeloid precursors and bone marrow evaluation showed hypercellular marrow with myeloid hyperplasia and basophilia, consistent with a chronic myeloproliferative neoplasm. Karyotyping revealed balanced reciprocal translocation t (9;22) and reverse‑transcriptase polymerase chain reaction (RT‑PCR) detected BCR‑ABL1 p210 fusion transcript, confirming the diagnosis of chronic phase CML in a background of beta thalassemia. The patient had elevated serum ferritin, indirect hyperbilirubinemia and mildly deranged transaminases, attributable to chronic transfusions and iron overload. After initiation of appropriate therapy, leukocyte counts normalized within one month along with disappearance of circulating immature myeloid precursors. This case highlights the importance of maintaining a high index of suspicion for CML in thalassemic patients with unexplained leukocytosis and splenomegaly, and underscores the need for integrated morphologic, cytogenetic and molecular work-up to distinguish disease progression from a second primary hematologic malignancy.

Lentiviral vectors (LVVs) are used as a viral gene therapeutic and were derived from human immunodeficiency virus subtype 1 (HIV-1). LVVs are used to deliver and induce the stable expression of transgenes through genome integration. Current clinical LVV delivery systems do not include HIV-1 major accessory genes; however, critical structural and non-structural HIV-1 proteins are encoded by the 4-plasmid combination that composes the 3rd generation LVV transduction systems. LVVs use HIV-1-like mechanisms for viral genome integration and both transgene delivery and expression. LVVs rely on host cell machinery to transcribe and translate transgenes for either knocking down disease-causing genes and/or supplying functional genes in a targeted disease. LVVs integrate into host intronic and intergenic regions due to genomic accessibility, but there are no known biases toward specific target integration motifs. Investigation of LVV integration has uncovered the generation of chimeric LVV-host transcripts and altered host transcript splicing patterns. Several Food and Drug Administration (FDA)-approved LVV-derived therapies are used for treating diseases ranging from beta thalassemia to sickle cell anemia. An increasingly popular application of LVV is in the generation of chimeric antigen receptor (CAR) T cell therapies, which change and enhance T cell antigen specificity and effector function in liquid cancers. In November 2023, all CAR T cell therapies were placed under FDA investigation due to higher-than-expected rates of malignant transformation, hospitalization, and death in treated individuals. LVV integrations driving oncogene expression could be a cause for malignancy development. Current methods for resolving LVV integration patterns are technically limited by the sequencing approach applied allowing for only limited characterization of LVV integration profiles and altered host gene regulation. A comprehensive understanding of LVV integration and its consequences is necessary for understanding how these events influence host cell gene regulation and splicing, possibly identifying tunable variables for enhanced positive clinical outcomes. Here, we review the development of LVV systems, what is known about LVV integration patterns, technologies used to characterize patterns of LVV integration, and what is understood about the subsequent impact on host cell gene regulation and its potential linkage to patient malignancies.

Background Multiply transfused thalassaemia patients can develop red cell immunization that can potentially cause haemolytic transfusion reactions and pose problems with compatibility testing for future transfusions. Previous research on red cell immunization in transfusion-dependent thalassaemia patients has not focused on paediatric groups. Objective This study aims to evaluate the prevalence of red cell immunization in transfusion dependent paediatric thalassaemia patients and identify its potential risk factors. Methods Clinical and serological data of transfusion-dependent thalassaemia patients aged 18 years and below were collected retrospectively from the Hospital Laboratory Information System. Results of antibody identification of the alloantibody and/or autoantibody were collected and analysed. Results Of the 32 patients included in our study, 17(53.1%), (11)34.4%, (2)6.3%, (2)6.3%, patients had HbE/β thalassaemia, β-thalassaemia major, alpha thalassaemia, thalassaemia intermedia/homozygous delta beta thalassaemia respectively. Out of 32 patients, five have developed antibodies against RBC antigens, giving rise to the prevalence of red cell immunization at 15.6%, in which 12.5% were alloantibodies and 3.1% were autoantibodies. The alloantibodies detected were anti E, anti-e, anti-c and alloantibody against lowfrequency antigen with an unknown specificity. The autoantibodies were nonspecific autoIgG. No significant association was observed between antibody formation and risk factors such as diagnosis, gender, blood group, age at first transfusion and number of packed cells transfused. Conclusion This study has successfully answered the prevalence of red cell immunization in multiply transfused paediatric thalassaemia. Our data showed prevalence of red cell immunization at 15.6%, in which 12.5% were alloantibodies and 3.1% were autoantibodies. We acknowledged that a bigger sample size with an extended study period is required. BJMS, Vol. 25 No. 01 January’26 Page : 143-149

Introduction: Iron deficiency anemia (IDA) and Thalassemia minor are the major causes of hypochromic and microcytic anemia. The present study was to determine the role of mentzer score in IDA and thalassemia trait patients from various parts of Pakistan who presented with microcytic hypochromic anemia at our centre. Materials and methods: This cross sectional study was conducted at the Dr. Essa Laboratory and Diagnostic Centre hematology department in Karachi from June 2024 to January 2025. The complete blood picture (CBC) was done by using XP-100 Sysmex analyzer. The mentzer score was calculated by dividing MCV with RBC. The score >13 was considered as an operational criterion for IDA. The mean and standard deviation were calculated for the continuous variables. The sensitivity, specificity, positive and negative predictive values, and diagnostic accuracy were calculated by SPSS version 25. Results: A total of 230 patients were included. The mean age of the patients was 22±14.4 years. A significantly low Hb with High RBC counts HbA2 levels were observed in patients with Thalassemia minor (p=<0.001). The Hb and RBC indices were significantly low in IDA patients(p=<0.001). The sensitivity of Mentzer index >13 in IDA patients was found to be 73.2%. Conclusion: Mentzer score can be used as a simple and easy to calculate index for the differentiation of IDA. However, Hb electrophoresis is the reliable test for the diagnosis of Thalassemia minor.

Angioid streaks, a rare defect of Bruch’s membrane, are most typically characterized by an asymptomatic course. However, when complications such as submacular hemorrhage or a neovascular membrane develop, visual acuity may deteriorate markedly, requiring therapeutic intervention. Angioid streaks can be associated with a number of systemic diseases, the most common being pseudoxanthoma elasticum, Paget’s disease, Ehlers–Danlos syndrome, beta thalassemia, and sickle cell anemia. This underscores the need for comprehensive systemic evaluation to identify potential comorbid conditions. We present the case of a 29-year-old patient in whom visual deterioration accompanied by image distortion was the first manifestation of angioid streaks complicated by a neovascular membrane. We demonstrate the positive therapeutic effects of intravitreal anti-vascular endothelial growth factor injections with ranibizumab. A total of five injections were required to stabilize the disease process, resulting in full visual acuity and complete resolution of subjective symptoms such as image distortion. Neoangiogenesis is the most common and most serious complication of angioid streaks. The fact that the disorder is rare, and at the same time linked to numerous systemic diseases, continues to hinder the development of standardized treatment protocols. The primary therapeutic method, yielding good results, is intravitreal anti-vascular endothelial growth factor treatment. Inhibition of vascular endothelial growth factor, the main mediator of angiogenesis and vascular permeability, plays a key role in stabilizing the disease. Moreover, early intervention is associated with markedly better outcomes and enables favorable anatomical and functional results.