De-novo ATR-16 syndrome associated with inherited hemoglobin Evanston causing HbH phenotype: a rare occurrence.

Abnormality of three α-globin genes, either deletion or point mutation results in symptomatic Hemoglobin H (HbH) phenotype. Most of such cases of α-globin defects are inherited from the parents, de-novo cases are exceedingly rare. Herein, a case of HbH is reported where the proband inherited one α-globin gene with a point mutation (αEvanston) from the mother. This was associated with large de-novo deletion of chromosome 16p13.3 resulting in α-thalassemia and mental retardation (ATR-16) syndrome. This deletion also encompassed two α-globin genes from chromosome 16, eventually leading to --/ααEvanston genotype, explaining the clinical presentation of the proband. The challenges in screening of such cases and confirming the molecular diagnosis along with the mode of inheritance has been discussed.

International Society for Cell & Gene Therapy Stem Cell Engineering Committee report on the current state of hematopoietic stem and progenitor cell-based genomic therapies and the challenges faced.

Genetic manipulation of hematopoietic stem cells (HSCs) is being developed as a therapeutic strategy for several inherited disorders. This field is rapidly evolving with several novel tools and techniques being employed to achieve desired genetic changes. While commercial products are now available for sickle cell disease, transfusion-dependent ß-thalassemia, metachromatic leukodystrophy and adrenoleukodystrophy, several challenges remain in patient selection, HSC mobilization and collection, genetic manipulation of stem cells, conditioning, hematologic recovery and post-transplant complications, financial issues, equity of access and institutional and global preparedness. In this report, we explore the current state of development of these therapies and provide a comprehensive assessment of the challenges these therapies face as well as potential solutions.

Health-related Quality of Life of Omani Adult Patients with ß-Thalassemia Major at Sultan Qaboos University Hospital.

Objectives: The impact of beta-thalassemia major (ß-TM) on health-related quality of life (HRQoL) in Oman is not yet known. Affected individuals suffer from a wide range of physical, mental, and social consequences due to the need for regular hospital visits for blood transfusions and complications related to iron overload. This study aimed to assess the HRQoL of adult patients with ß-TM attending a single tertiary care center in Muscat, Oman, to identify factors influencing Omani patients' QoL for improved management and counseling. Methods: A cross-sectional study was conducted among adult patients (≥ 18 years) with ß-TM at Sultan Qaboos University Hospital between September and November 2022. A validated Arabic version of the self-reported 36-item short-form health survey was used to determine HRQoL. Results: A total of 78 patients with ß-TM were enrolled in the study; 53.8% were male and the mean age was 26.0±0.8 years, ranging from 21-53 years. Most patients were from Al Batinah North governorate (n = 21; 26.9%) and Muscat (n = 20; 25.6%), unmarried (n = 44; 56.4%), did not have university-level education (n = 45; 57.7%), and were unemployed (n = 44; 56.4%). The HRQoL domain with the highest score was role limitations due to emotional problems (median score = 100), while general health and vitality received the lowest scores (mean scores were 60.2±15.9 and 59.1±20.5, respectively). Several variables were associated with better HRQoL in certain domains, including being married, having a high level of education, being employed, exercising regularly, and receiving family support (p < 0.05). However, iron overload and having ≥ 3 ß-TM-related disease complications were associated with poorer general health scores (p = 0.031 and 0.038, respectively), while a history of mental issues was associated with poorer scores in six out of eight HRQoL domains (p < 0.05). Moreover, negative perceptions regarding the social impact of the disease including delayed marriage, workplace difficulties, and reduced academic achievement were associated with poorer HRQoL in various domains (p < 0.05). Conclusions: Although the studied sample reported generally good QoL, several factors were found to affect HRQoL in various domains. Healthcare providers should prioritize maintaining acceptable iron overload levels in Omani patients with ß-TM to help avoid the development of disease-related complications, thereby ensuring better control of their clinical conditions and consequently improving their HRQoL.

The relationship between liver stiffness by two-dimensional shear wave elastography and iron overload status in transfusion-dependent patients.

Increased liver stiffness (LS) can be result of increased liver iron concentration (LIC) which may not yet be reflected in the liver fibrotic status. The objective of our study was to examine relationship between hemochromatosis, LS, and serum ferritin level in transfusion-dependent patients. We recruited all 70 transfusion-dependent patients, whose median age was 15, referred for evaluating LIC status by magnetic resonance imaging (MRI) followed by two-dimensional ultrasonography shear wave elastography (2D-SWE). Thalassemia beta affected the majority of the patients. The optimal cut point for prediction of severe hemochromatosis using median SWE (kPa) and SWV (m/s) was ≥ 7.0 kPa and ≥ 1.54 m/s, respectively, with sensitivity of 0.76 (95% confidence interval [CI] 0.55, 0.91) and, specificity of 0.69 (95%CI 0.53, 0.82). When combing the optimal cut point of SWE (kPa) at ≥ 7.0 and serum ferritin ≥ 4123 ng/mL, the sensitivity increased to 0.84 (95%CI 0.64, 0.95) with specificity of 0.67 (95%CI 0.50, 0.80), positive predictive value (PPV) of 0.60 (95%CI 0.42, 0.76), and negative predictive value (NPV) of 0.88 (95%CI 0.71, 0.96). Simultaneous tests of 2D-SWE and serum ferritin for prediction of severe hemochromatosis showed the highest sensitivity of 84% (95%CI 0.64-0.95), as compared to 2D-SWE alone at 76% (95%CI 0.55, 0.91) or serum ferritin alone at 44% (95%CI 0.24-0.65). We recommend measuring both 2D-SWE and serum ferritin in short interval follow up patients. Adding 2D-SWE to management guideline will help in deciding for aggressive adjustment of iron chelating medication and increased awareness of patients having severe hemochromatosis.

A Rare Case of De Novo Beta-Thalassemia Diagnosed by Whole-Genome Sequencing in an Ethnically Danish Newborn.

In 2020, a 2-month-old ethnically Danish girl was diagnosed with ß-thalassemia after presenting with persistent jaundice. The peripheral blood smear showed significant aniso- and poikilocytosis, increased number of reticulocytes and erythroblastosis. Trio analysis of the index patient and both parents was performed by whole-genome sequencing. Here, both parents were found normal, however the analysis revealed an apparently de novo HBB:c.444A > C variant in the child. The child has recently been discharged three months after a successful bone marrow transplantation with a matched sibling-donor.

Prevalence and risk factors predisposing low bone mineral density in patients with thalassemia.

Background: A common complication of thalassemia is secondary osteoporosis. This study aimed to assess the prevalence and factors associated with low BMD in thalassemic patients. Method: This is a cross-sectional study. Eligible patients were males aged within 18-49 years or premenopausal women diagnosed with thalassemia in Chiang Mai University Hospital between July 2021 and July 2022. The diagnosis of low BMD by dual-energy x-ray absorptiometry (DXA) was defined as a Z-score of -2.0 SD or lower in either the lumbar spine or femoral neck. Clinical factors associated with low BMD were analyzed using a logistic regression model. Results: Prevalence of low BMD was 62.4% from 210 patients with a mean age of 29.7 ± 7.6 years. The predominant clinical characteristics of low BMD thalassemia patients were being female, transfusion-dependent (TDT) and a history of splenectomy. From multivariable analysis, the independent variables associated with low BMD were transfusion dependency (odds ratio, OR 2.36; 95%CI 1.28 to 4.38; p=0.006) and body mass index (BMI) (OR 0.71; 95%CI 0.61 to 0.82; p<0.001). Among patients with low BMD, we observed a correlation between a Z-score with low IGF-1 levels (ß=-0.42; 95% CI -0.83 to -0.01; p=0.040), serum phosphate levels (ß=0.40; 95% CI 0.07 to 0.73; p=0.016) and hypogonadism (ß=-0.48, 95% CI -0.91 to -0.04, p=0.031). Conclusion: This study found a prevalence of low BMD in 62.4% of subjects. Factors associated with low BMD were TDT and BMI. Within the low BMD subgroup, hypogonadism, serum phosphate and low serum IGF-1 levels were associated with a lower Z-score.

Autosomal Recessive Hyper-IgE Syndrome in a Child With Beta Thalassemia Trait: A Case Report.

Autoimmune diseases are multifaceted disorders, and their coexistence with other conditions can present unique challenges in diagnosis and management. Here, we report a rare case of autosomal recessive hyper-IgE syndrome (AR-HIES) in a child with beta thalassemia trait. AR-HIES is a distinct immunodeficiency disorder characterized by severe eczema and recurrent bacterial and viral infections, particularly affecting the sinopulmonary system. This case highlights the importance of recognizing and managing the co-occurrence of rare genetic conditions, as it can impact treatment strategies and familial counseling. This unique case of AR-HIES in a child with beta thalassemia trait underscores the complexity of autoimmune disorders and the need for comprehensive evaluation in patients presenting with multiple clinical manifestations.

Development of pre-implantation genetic testing protocol for monogenic disorders (PGT-M) of Hb H disease.

Hb H disease is the most severe form of α-thalassemia compatible with post-natal life. Compound heterozygous α0-thalassemia- SEA deletion/α+-thalassemia- 3.7kb deletion is the commonest cause of Hb H disease in Thailand. Preimplantation genetics testing for monogenic disorders (PGT-M) is an alternative for couples at risk of the disorder to begin a pregnancy with a healthy baby. This study aims to develop a novel PCR protocol for PGT-M of Hb H disease- SEA/-3.7kb using multiplex fluorescent PCR. A novel set of primers for α+-thalassemia- 3.7kb deletion was developed and tested. The PCR protocol for α0-thalassemia- SEA deletion was combined for Hb H disease- SEA/-3.7kb genotyping. The PCR protocols were applied to genomic DNA extracted from subjects with different thalassemia genotypes and on whole genome amplification (WGA) products from clinical PGT-M cycles of the families at risk of Hb Bart's. The results were compared and discussed. The results showed three PCR products from α+-thalassemia- 3.7kb primer set, and three from α0thalassemiaSEA primer set. The results were consistent with the known thalassemia genotypes. The novel -α3.7 primers protocol was also tested on 37 WGA products from clinical PGT-M cycles giving accurate genotyping results and a satisfying amplification efficiency with the ADO rates of 2.7%, 0%, and 0% for HBA2, HBA1, and internal control fragments, respectively. This novel PCR protocol can precisely distinguish Hb H disease- SEA/-3.7kb from other genotypes. Additionally, this is the first PCR protocol for Hb H disease- SEA/-3.7kb which is optimal for PGT-M.

The German sickle cell disease registry reveals a surprising risk of acute splenic sequestration and an increased transfusion requirement in patients with compound heterozygous sickle cell disease HbS/ß-thalassaemia and no or low HbA expression.

Patients with sickle cell disease (SCD) in Germany exhibit a substantial genetic diversity in the ß-globin genotype. Data collected by the national German SCD registry reflect this diversity and allowed us to analyze the phenotypes associated with different SCD genotypes. Our study focused on 90 patients with HbS/ß-thalassaemia (HbS/ß-thal) and compared these to patients with HbSS and HbSC. Patients with HbS/ß-thal were classified into three groups: HbS/ß0-thal (no HbA), HbS/ß+-thal (HbA < 14%), and HbS/ß++-thal (HbA≥14%). In comparison to HbSS, patients with HbS/ß++-thal had higher Hb-levels, lower hemolytic activity and rarely required red blood cell transfusions. HbS/ß0-thal and HbS/ß+-thal closely resembled each other and are jointly referred to as HbS/ß0/+-thal. Compared to HbSS, patients with HbS/ß0/+-thal experienced a similar frequency of vasoocclusive crises and degree of hemolysis. However, the frequency of red blood cell transfusions (0.6 vs. 0.39/year, p = .0049) and splenic sequestration crises (42.4 vs. 15.5% of patients, p = 3.799e-05) was higher in HbS/ß0/+-thal than in HbSS, but close to zero in HbS/ß++-thal. In conclusion, the level of HbA expression determines the phenotype of HbS/ß+-thal. HbS/ß-thal expressing no or little HbA is hematologically similar to HbSS, but causes a previously unknown high risk of splenic sequestration.

Global, regional, and national burden of thalassemia during 1990-2019: A systematic analysis of the Global Burden of Disease Study 2019.

INTRODUCTION: Thalassemia represents a significant public health challenge globally. However, the global burden of thalassemia and the disparities associated with it remain poorly understood. Our study aims to uncover the long-term spatial and temporal trends in thalassemia at global, regional, and national levels, analyze the impacts of age, time periods, and birth cohorts, and pinpoint the global disparities in thalassemia burden. METHODS: We extracted data on the thalassemia burden from the Global Burden of Disease Study (GBD) 2019. We employed a joinpoint regression model to assess temporal trends in thalassemia burden and an age-period-cohort model to evaluate the effects of age, period, and cohort on thalassemia mortality. RESULTS: From 1990 to 2019, the number of thalassemia incident cases, prevalent cases, mortality cases, and disability-adjusted life years (DALYs) decreased by 20.9%, 3.1%, 38.6%, and 43.1%, respectively. Age-standardized rates of incidence, prevalence, mortality, and DALY declined across regions with high, high-middle, middle, and low-middle sociodemographic index (SDI), yet remained the highest in regions with low SDI and low-middle SDI as well as in Southeast Asia, peaking among children under five years of age. The global prevalence rate was higher in males than in females. The global mortality rate showed a consistent decrease with increasing age. CONCLUSION: The global burden of thalassemia has significantly declined, yet notable disparities exist in terms of gender, age groups, periods, birth cohorts, SDI regions, and GBD regions. Systemic interventions that include early screening, genetic counseling, premarital health examinations, and prenatal diagnosis should be prioritized in regions with low, and low-middle SDI, particularly in Southeast Asia. Future population-based studies should focus specifically on thalassemia subtypes and transfusion requirements, and national registries should enhance data capture through newborn screening.

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.

Fat Embolism Syndrome Mimicking Thrombotic Thrombocytopenic Purpura in a Patient With Hemoglobin S/Beta-Thalassemia.

Thrombotic microangiopathies cause ischemic organ damage and require urgent management for a favorable prognosis. Fat embolism syndrome from bone marrow necrosis is a rare and unique pathology that carries a high mortality rate. It can mimic thrombotic microangiopathies such as thrombotic thrombocytopenic purpura (TTP). Herein, we present a patient with sickle cell-beta-thalassemia who initially presented with a vaso-occlusive crisis, lab evidence of hemolysis, schistocytes and thrombocytopenia who developed acute encephalopathy with respiratory distress, consistent with TTP. She was found to have multiple infarcts in the brain. She was intubated and underwent plasma and red cell exchange. Bone marrow biopsy confirmed marrow necrosis from her vaso-occlusive crisis and subsequently, fat embolism syndrome. Here, we discuss the complex presentation and the complications of fat embolism from bone marrow necrosis and how it can mimic TTP.

Characterization and Clinical Assessment of a Peculiar Case of Hemolytic Anemia.

Thalassemic diseases are characterized by a reduced (ß+) or absent (ß0) synthesis of the globin chains of hemoglobin (Hb) due to genetic mutations. ß-thalassemia was more frequent in the Mediterranean area, but now it is diffused worldwide. Three possible genetic forms can be distinguished: ß0/ß0, the most severe (Cooley's disease); ß0/ß+ of intermediate severity; ß+/ß+ associated with ß-thalassemia intermedia or minor. Recently, a clinical non-genetic classification has been proposed: transfusion-dependent thalassemia (TDT), requiring regular lifetime blood transfusions, and non-transfusion-dependent thalassemia (NTDT), requiring occasional transfusions to manage acute cases. In this report, we studied a patient whose blood count indicated a severe anemia but also showed thrombocytosis, leukocytosis, and an elevated number of nucleated red blood cells (NRBC). These altered blood parameters suggested initially a possible diagnosis of hemoglobinopathy or myeloproliferative syndrome. The molecular and genetic analyses demonstrated the presence of HbF (5.3%) and HbA2 (7.7%) and the presence of the homozygote mutation (IVS1.6T>C) in the ß-globin gene. According to these data, a diagnosis of ß-thalassemia intermedia form has been proposed. Nevertheless, the clinical condition, the presence of thrombocytosis, leukocytosis, an elevated number of NRBC, and the frequent blood transfusions lead to reclassification of the patient as TDT subject. Consequently, this result suggests that a unique genotype-phenotype correlation is not possible in the presence of ß+mutations since other concomitant pathologies can exacerbate the disease.

Appropriateness of the EQ-5D-5L in capturing health-related quality of life in individuals with transfusion-dependent ß-thalassemia: a mixed methods study.

BACKGROUND: Individuals with transfusion-dependent ß-thalassemia (TDT) experience symptoms and functional impacts that reduce their health-related quality of life. However, EQ-5D-derived health utility index scores in TDT often indicate good HRQoL, suggesting the EQ-5D may not adequately capture the impact of TDT. This study explored the disease and treatment burden of TDT and examined the appropriateness of the EQ-5D-5L descriptive system (DS) in measuring HRQoL in TDT. METHODS: Adults with TDT in the United Kingdom, United States, and France completed a background questionnaire and EQ-5D-5L DS, followed by 60-minute semi-structured interviews on symptoms and HRQoL impacts of TDT (concept elicitation) and appropriateness of EQ-5D-5L DS (cognitive debrief). Transcribed interviews were analyzed using thematic and content analyses. The relationship between TDT symptoms and impacts were summarized in a conceptual model. EQ-5D-5L DS was mapped to concepts identified in the qualitative data to assess its capture of HRQoL concepts. Participants' EQ-5D-5L DS scores were compared to their qualitative descriptions for each dimension to assess their concordance. RESULTS: Thirty participants in the United States (n = 14 [46.7%]), United Kingdom. (n = 12 [40.0%]), and France (n = 4 [13.3%]) completed the study (73.3% female; mean age = 28.4 years [standard deviation (SD) = 5.1]; mean annual red blood cell transfusion [RBCT] frequency = 18.4 [SD = 7.6]). Participants reported TDT symptoms and impacts on HRQoL, all fluctuating across the RBCT cycle. EQ-5D-5L DS did not fully capture 11 of 16 (68.8%) HRQoL concepts reported. Most participants (n = 20/27 [74.1%]) reported that EQ-5D-5L DS did not capture important aspects of living with TDT, and 42.9% (n = 12/28) reported negative/neutral overall impressions of EQ-5D-5L DS. The highest degree of discordance between participants' qualitative data and EQ-5D-5L DS dimension scores was observed with mobility (42.3%) and self-care (34.6%), where the qualitative descriptions relating to these dimensions were worse than their quantitative scores. CONCLUSION: Current findings suggest that EQ-5D-5L DS lacks content validity and the derived health utility index score may not fully represent the burden of disease in TDT.

Red Cell Alloimmunisation Among Sickle Cell Disease and Thalassemia Patients Following Rh- and K-Matched Red Cell Transfusion in Southwestern Saudi Arabia: A Multicenter Study.

Background: Alloimmunisation remains a major consequence of blood transfusion among sickle cell disease (SCD) and thalassemia patients due to the exposure to non-self-red blood cell (RBC) antigen. The complication is associated with transfusion reactions and delayed transfusion procedure because of the difficulty of finding compatible blood. This study aims to determine the prevalence of alloimmunisation to RBC and alloantibody specificities among SCD and thalassemia patients in, an endemic area of SCD and thalassemia, Jazan province of Saudi Arabia, from three major hospitals. Methods: This is a retrospective, multicenter cross-sectional study conducted on 1027 patients with SCD and thalassemia, which received Rh/K matched transfusions in 2019 in the three centers. Demographic data and medical records of participants from three transfusion institutions were collected and analysed. Results: A total of 1027 were enrolled in the cohort; 906 (88.2%) and 121 (11.8%) patients with SCD and thalassemia, respectively. There were 483 (47%) males and 544 (53%) females with median age of 15 (range 1-48). Among the studied population, 78 were alloimmunised with an overall alloimmunisation rate of 7.6%. These patients developed a total of 108 alloantibodies, and anti-E was the most detected antibody (25.9%) followed by anti-K (24.1%). Conclusion: The overall rate of alloimmunisation to RBC antigen among the studied population in Jazan was low compared to other areas in the country. Most alloantibodies detected were against E and K antigens. The knowledge of most encountered alloantibodies in our population will aid in selecting the most appropriate antigen-negative red cells. Further research, however, is needed to explore factors associated with residual risk of alloimmunisation in these patients.

Prevalence of HIV, hepatitis B and hepatitis C infections among patients with thalassemia attending a tertiary care (rural) hospital.

Introduction: The Sunderban area of West Bengal is home to tribal and religious minorities inhabiting various islands. There is a high prevalence of thalassemia among poverty-stricken residents of this region living with meagre health care facilities. This work was planned to determine the proportion of four viral transfusion-transmitted infections (TTIs): HIV-1, HIV-2, hepatitis B virus (HBV) and hepatitis C virus (HCV) among thalassemia patients attending the sole rural medical college in the region. Materials and Methods: Thalassemia patients (n = 359, age ranging from 1 year to 60 years) attending the thalassemia clinic or being admitted to the indoor facilities for better management were included in the study. Only patients diagnosed with high-performance liquid chromatography (HPLC) and with classical clinical features were included in the study. Blood samples of these patients were tested for HIV as per NACO protocol. For HBV and HCV, samples were first tested serologically; reactive samples were collected and sent in the cold chain to a higher centre for nucleic acid amplification testing (NAAT) for qualitative and quantitative estimation. Clinical and laboratory data was collected, patients were followed up for complications and hospitalisation during the study period, and statistical analysis was performed. Results: Majority of our patients had E-beta-thalassemia (245, 59.81%), followed by beta-thalassemia major (102, 28.30%). NAAT-confirmed HCV infection (14.21%) infection was the most common, followed by HBV (2.51%), and lastly by HIV-1 (0.58%) infection. Among infected thalassemia patients, the mean HCV RNA was 741063 ± 438514.67 IU/ml while the mean HBV DNA level was 4082863 ± 7298514 IU/ml. Co-infections of HIV-1 and HCV and that of HBV and HCV were noted in one patient each (0.28%). HCV-related liver disease (14.21%) and growth retardation (10.31%) were the most typical complication noted, and death occurred in five patients (1.39%) during the study period. Conclusion: Primary care physicians should know HCV infection is the most common TTI among thalassemia patients in rural eastern India.

Correlation between plasma biochemical parameters and cardio-hepatic iron deposition in thalassemia major patients.

INTRODUCTION: Major Thalassemia patients suffer from iron overload and organ damage, especially heart and liver damage. Early diagnosis and treatment with a chelator can reduce the complications and mortality of iron overload. Therefore, we aimed to investigate the biochemical and hematological predictors as an alternative and indirect indicator of iron deposition in heart and liver cells in comparison with the MRI T2* method as the gold standard. MATERIAL AND METHOD: MRI T2* was evaluated in the heart and liver tissues of 62 major beta-thalassemia patients undergoing regular transfusion and chelator therapy. Biochemical and hematological factors were also measured, including serum ferritin, serum electrolytes, liver enzymes, hemoglobin, blood glucose, and serum magnesium. The correlation between these factors was assessed using statistical evaluations. RESULT: Serum ferritin had a positive and significant correlation with liver siderosis based on MRI T2* (p-value = .015), and no significant association was observed with cardiac siderosis (p-value = .79). However, there was a significant positive correlation between cardiac iron deposition and fasting blood sugar level (p-value = -.049), and plasma level of liver enzymes (alanine aminotransferase (ALT) (p-value = .001), aspartate aminotransferase (AST ((p-value = .01)). Moreover, there was a significant negative correlation between cardiac iron overload and plasma magnesium level (p-value = .014). According to MRI T2*, there was no significant correlation between cardiac and hepatic iron overload (p value = .36). CONCLUSION: An increase in blood sugar or liver enzymes and a decrease in serum magnesium was associated with an increase in cardiac iron overload based on MRI T2*. Liver iron overload based on MRI T2* had a significant correlation with serum ferritin.

Genetic Correlation of HBB, HFE and HAMP Genes to Endocrinal Complications in Egyptian Beta Thalassemia Major Patients.

Iron loading is regarded as the primary cause of endocrine abnormalities in thalassemia major patients. Thus, the purpose of the current research was to explore the impact of thalassemia genotypes, hepcidin antimicrobial peptide (HAMP) and hereditary hemochromatosis (HFE) gene variants, and hepcidin expression on serum ferritin and endocrinal complications in thalassemia patients. The study comprised fifty beta-thalassemia cases and fifty age- and sex-matched controls. Genotyping of the Beta-globin gene (HBB), HAMP, and exon 2 of the HFE gene was performed using Sanger sequencing. C282Y (c.845G > A) variant of the HFE gene was determined by PCR-RFLP. Hepcidin mRNA expression was assessed by qRT-PCR. Biochemical and hormonal studies were done for all patients. Hypogonadism and short stature were found in 56% and 20% of the investigated cases, respectively. Molecular studies reported a statistically higher frequency of the HAMP variant c.-582A > G in thalassemic patients than controls. Significant downregulation of hepcidin expression was found in cases compared to healthy subjects that was significantly associated with short stature. Considering the thalassemia alleles, the IVSI.1G > A (ß0) allele was statistically related to hypogonadism. Our results proposed that thalassemia genotypes and downregulated hepcidin expression were the potential risk factors for endocrinopathies in our cases. We also demonstrated an increased incidence of the HAMP promoter variant c.- 582A > G that might have a role in the pathogenesis of iron overload in thalassemic cases. Significant downregulation of hepcidin expression, that contributes to increased iron burden, could be used as a future therapeutic target in these patients.

A Novel ß-Globin Variant, Hb Odder [HBB: C.316C > G; CD105 (Leu > Val)].

We report the discovery of a novel ß-globin gene variant, Hb Odder, characterized by a single nucleotide substitution; HBB:c.316C > G; CD105 (Leu > Val). This variant emerged incidentally during routine HbA1c measurements for diabetes monitoring. The patient exhibited no clinical or biochemical evidence of anemia or hemolysis. Our data on this variant suggest that Hb Odder is benign, regrettably limitations in our data make formal evaluations of stability and oxygen affinity impossible; additionally this emphasizes the importance of considering hemoglobin variants in the differential diagnosis of abnormal Hb A1c levels and suggest that laboratories should use alternative methods for the correct measurement of Hb A1c when hemoglobin variants interfere with diabetes monitoring. Notably, three other mutations have been described at codon 105 of the ß globin chains and correspond to three Hb variants with different characteristics: Hb South Milwaukee, Hb Bellevue IV and Hb St. George.

Global longitudinal strain by cardiac magnetic resonance is associated with cardiac iron and complications in beta-thalassemia major patients.

BACKGROUND: The aim of this cross-sectional study was to investigate the association of left ventricular (LV) strain parameters with demographics, clinical data, cardiovascular magnetic resonance (CMR) findings, and cardiac complications (heart failure and arrhythmias) in patients with ß-thalassemia major (ß-TM). METHOD: We considered 266 ß-TM patients (134 females, 37.08 ±â€¯11.60 years) consecutively enrolled in the Extension-Myocardial Iron Overload in Thalassemia (E-MIOT) project and 80 healthy controls (50 females, mean age 39.77 ±â€¯11.29 years). The CMR protocol included cine images for the assessment of global longitudinal strain (GLS), global circumferential strain (GCS), and global radial strain (GRS) using feature tracking (FT) and for the quantification of LV function parameters, the T2* technique for the assessment of myocardial iron overload, and late gadolinium enhancement (LGE) technique. RESULTS: In comparison to the healthy control group, ß-TM patients showed impaired GLS, GCS, and GRS values. Among ß-TM patients, sex was identified as the sole independent determinant of all LV strain parameters. All LV strain parameters displayed a significant correlation with LV end-diastolic volume index, end-systolic volume index, mass index, and ejection fraction, and with the number of segments exhibiting LGE. Only GLS exhibited a significant correlation with global heart T2* values and the number of segments with T2* < 20 ms. Patients with cardiac complications exhibited significantly impaired GLS compared to those without cardiac complications. CONCLUSION: In patients with ß-TM, GLS, GCS, and GRS were impaired in comparison with control subjects. Among LV strain parameters, only GLS demonstrated a significant association with cardiac iron levels and complications.