Thalassemia Patients Research Articles

Bone and Joint Involvement in Beta Thalassemic Patients: A Cross-sectional Study

Bone and Joint Involvement in Beta Thalassemic Patients: A Cross-sectional Study

Existing Tubular Injury in β-Thalassemia Major Patients Receiving Iron Chelating Agents with Normal Creatinine Level in East Java, Indonesia.

Patients suffering from thalassemia are recipients of routine transfusions leading to hemosiderosis. Taking iron chelating agents is mandatory. Several studies have shown different results regarding the occurrence of kidney complications in thalassemia patients who received iron-chelating agents. In this study, we were looking for kidney complications by examining human NAG urine/serum and NGAL urine/serum in thalassemia community in East Java community. The study was conducted cross-sectionally in the thalassemia community in East Java with a total sample of 91 patients aged 13-48 years. All thalassemia patients filled in demographic data, transfusion routines, duration of taking iron chelating agents, and length of time diagnosed with thalassemia. Laboratory tests included routine blood tests for ferritin, ureum, serum creatinine, human NAG urine or serum, and human NGAL urine or serum. Comparison tests (t-test, Mann-Whitney, and ANOVA, Kruskal-Wallis) were conducted to see if there were significant differences in the levels of human NAG urine and human NGAL urine serum based on age, sex, blood group, duration of transfusion, routine of transfusion, duration of taking iron chelating agents, and types of iron chelating drugs. Multivariate analysis was conducted to see whether some of these categories were related to abnormalities in human NAG urine or serum and human NGAL urine or serum. All 91 patients had normal creatinine values, yet some had abnormal serum NAG. There is a significant difference in urine human NAG and urine human NGAL levels at ages over 23 years (p = 0.05 and p = 0.01). Significant differences in human NGAL serum were also found in working and student patients (p = 0.028). Serum NGAL also differed in those taking deferasirox (p = 0.030) and significantly different human NGAL urine was also found in iron overload status (Ferritin ≥ 1000 ng.ml) (p = 0.006). There is no difference between human NAG urine/serum and human NGAL urine/serum based on sex, body mass index, blood type, hemoglobin less than 10 g/dl, routine transfusion once a month, duration of using iron chelation for more than 10 years, or splenomegaly status (splenomegaly, splenectomy, or no splenomegaly). The multivariate logistic regression results showed that age above 23 was a factor associated with abnormal urine human NAG levels (aOR = 3.79, 95% CI = 1.08-13.28). Students (aOR = 4.89, 95% CI = 1.48-16.16) with ages above 23 years (aOR = 3.69, 95% CI = 1.09-12.43) showed higher risk for an abnormal serum human NGAL levels. Patients with beta-thalassemia major exhibit noticeable tubular damage. Further research is encouraged to determine other factors behind tubular damage in the thalassemia community, particularly in Indonesia.

Genotype-phenotype correlation analysis of patients with thalassemia in Quanzhou city, Southeast of China

BackgroundThe carrying rate of thalassemia is high in Quanzhou city. However, there are few large-scale studies on the correlation analysis between genotype and phenotype of thalassemia in Quanzhou. In this study, the genotype and phenotype data of 1076 individuals with thalassemia in Quanzhou city were analyzed to provide reference data for screening and diagnosis of thalassemia in this region. Material and MethodsReverse dot blot hybridization (RDB-PCR), Gap-PCR and nested PCR were used to detect the thalassemia genotype. Clinical and hematological parameters of 1076 individuals of thalassemia were collected to analyze the correlation between genotype and phenotype. ResultsAmong 2997 subjects, 1076 cases diagnosed as thalassemia gene carrier or patients, with detection rate 35.9%, among which Southeast Asian deletion (--SEA) / αα was the most common α-thalassemia genotype (48.4%) and one rare genotype was detected: HKαα/--SEA (0.1%). Subjects with thalassemia alone showed the least severe symptoms of anemia with higher red blood cell count (RBC) and hemoglobin (Hb), lower red blood cell distribution width (RDW) than those with iron deficiency (ID) or iron overload (IO) (p<0.05). The Hb, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH) levels in gene carriers of α-thalassemia were higher than those of β-thalassemia, while RBC, RDW and serum ferritin (SF) levels were lower than the later(p<0.05). Among individuals with --SEA/αα, the Hb, MCV, MCH, mean corpuscular hemoglobin concentration (MCHC) and SF levels of subjects≥19 years old were higher than those of ≤18 years old. For cases ≥19 years old, the RBC, Hb and SF levels in male were higher than that in female, while MCHC level was lower than female(p<0.05). ConclusionThe difference of hematological phenotypes in patients with thalassemia is not only affected by their genotype, but also the influence of gender and age.

Knowledge, Attitude and Practice of Conventional Medicine Among Thalassaemia In Malaysia: Conceptual paper

Thalassaemia is chronic hereditary blood disorder. Medication has extended patients' lifespans, but research on their quality of life is scarce due to psychological impacts and medication adherence issues. The objective is to develop and validate a survey assessing the knowledge, attitude, and practice of Malaysian thalassaemia patients towards medication. We will use an exploratory mixed-methods approach with ethical approval from UiTM. Phase I involves semi-structured interviews with thalassaemia patients. Phase II focusses on creating and validating KAP instruments with expert panels and pilot testing. The tools will help medical professionals gather data to improve treatment compliance.

Whole Blood Transcriptome Analysis in Congenital Anemia Patients

Congenital anemias include a broad range of disorders marked by inherent abnormalities in red blood cells. These abnormalities include enzymatic, membrane, and congenital defects in erythropoiesis, as well as hemoglobinopathies such as sickle cell disease and thalassemia. These conditions range in presentation from asymptomatic cases to those requiring frequent blood transfusions, exhibiting phenotypic heterogeneity and different degrees of severity. Despite understanding their different etiologies, all of them have a common pathophysiological origin with congenital defects of erythropoiesis. We can find different types, from congenital sideroblastic anemia (CSA), which is a bone marrow failure anemia, to hemoglobinopathies as sickle cell disease and thalassemia, with a higher prevalence and clinical impact. Recent efforts have focused on understanding erythropoiesis dysfunction in these anemias but, so far, deep gene sequencing analysis comparing all of them has not been performed. Our study used Quant 3′ mRNA-Sequencing to compare transcriptomic profiles of four sickle cell disease patients, ten thalassemia patients, and one rare case of SLC25A38 CSA. Our results showed clear differentiated gene map expressions in all of them with respect to healthy controls. Our study reveals that genes related to metabolic processes, membrane genes, and erythropoiesis are upregulated with respect to healthy controls in all pathologies studied except in the SLC25A38 CSA patient, who shows a unique gene expression pattern compared to the rest of the congenital anemias studied. Our analysis is the first that compares gene expression patterns across different congenital anemias to provide a broad spectrum of genes that could have clinical relevance in these pathologies.

Health-related quality of life and associated factors among children with Transfusion-dependent β-thalassaemia: a cross-sectional study in Guangxi Province

BackgroundTransfusion-dependent β-thalassemia (TDT) is a severe inherited disorder. Without regular treatment, patients with TDT experience complications that can significantly shorten life expectancy and severely impact both their quality of life and that of their families. The condition has attracted significant attention in global health discussions. Due to the challenges of blood supply shortages, the high costs of iron chelation therapy, and hematopoietic stem cell transplantation (HSCT), TDT presents a serious health risk to patients and imposes a substantial burden on families and society. However, research on the health-related quality of life (HRQoL) of thalassemia patients in China remains limited. This study evaluated the factors affecting the HRQoL of these patients, with the goal of developing strategies to improve their quality of life.MethodsIn this cross-sectional study, children with TDT were recruited from five treatment centers in Guangxi, a province with a high prevalence of thalassemia in China. Structured questionnaires were employed to gather relevant data on sociodemographic variables, disease characteristics, treatments, and associated costs. The HRQoL was assessed using the Transfusion-Dependent Quality of Life (TranQoL) questionnaire, with a proxy version for patients aged 0–11 years and a child version for those aged 12–18 years.ResultsThe study included 418 participants, yielding an overall TranQoL score of 60.6 ± 16.3 among thalassemia patients. Multiple linear regression analysis revealed a negative correlation (P < 0.05) between overall TranQoL scores and several factors: increasing patient age, the presence of multiple thalassemia patients within a family, and undergoing HSCT. Conversely, adherence to regular treatment was positively correlated with higher TranQoL scores (P < 0.05).ConclusionThe study demonstrates that HRQoL among Chinese patients with TDT is at a low level. Age, treatment adherence, family support, and socioeconomic status were identified as key determinants influencing HRQoL. It is essential to further enhance and optimize health insurance policies and medical services to support comprehensive treatment strategies for these patients.

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Role of Transient Elastography in Pediatric Transfusion Dependent Thalassemia Patients from Lower Socioeconomic Strata and its Correlation with Serum Ferritin: A Cross-Sectional Study

Exploring alterations of gut/blood microbes in addressing iron overload-induced gut dysbiosis and cognitive impairment in thalassemia patients

Iron overload causes cognitive impairment in thalassemia patients. The gut-brain axis plays an important role in cognitive function. However, the association between gut/blood microbiome, cognition, and iron burden in thalassemia patients has not been thoroughly investigated. We aimed to determine those associations in thalassemia patients with different blood-transfusion regimens. Sixty participants: healthy controls, transfusion-dependent thalassemia (TDT) patients, and non-transfusion-dependent (NTDT) patients, were recruited to evaluate iron overload, cognition, and gut/blood microbiome. TDT patients exhibited greater iron overload than NTDT patients. Most thalassemia patients developed gut dysbiosis, and approximately 25% of the patients developed minor cognitive impairment. Increased Fusobacteriota and Verrucomicrobiota with decreased Fibrobacterota were observed in both TDT and NTDT groups. TDT patients showed more abundant beneficial bacteria: Verrucomicrobia. Iron overload was correlated with cognitive impairment. Increased Butyricimonas and decreased Paraclostridium were associated with higher cognitive function. No trace of blood microbiota was observed. Differences in blood bacterial profiles of thalassemia patients and controls were insignificant. These findings suggest iron overload plays a role in the imbalance of gut microbiota and impaired cognitive function in thalassemia patients. Harnessing probiotic potential from those microbes could prevent the gut-brain disturbance in thalassemia patients.

Immunological Changes and Complement Proteins in Major Thalassemia Patients Proteins Post-Splenectomy

Background: Thalassemia is one of the most prevalent genetic disorders worldwide, with infections being a leading cause of mortality due to compromised immune function. Specific Background: Prior studies suggest that major thalassemia patients are highly susceptible to microbial infections, possibly due to altered immunological profiles, particularly immunoglobulin (IgG, IgM) and complement (C3, C4) levels. Knowledge Gap: However, the specific immunological changes pre- and post-splenectomy in these patients remain underexplored. Aims: This study aims to assess the levels of immunoglobulins (IgG and IgM) and complement proteins (C3 and C4) in major thalassemia patients both before and after splenectomy compared to healthy controls. Results: Our analysis of 50 thalassemia patients (34 males, 16 females) and 30 healthy individuals revealed that thalassemia patients exhibited significantly lower levels of C3 and C4 (88.52±24.49, 21.20±6.66) compared to healthy controls (123.50±19.04, 32.87±9.77). IgG and IgM were elevated in patients (1288.12±467.87, 153.46±51.29) compared to controls (1129.93±295.96, 148.67±50.17). Post-splenectomy, patients showed a significant decline in IgG (1001.56±154.14) and IgM (110.08±25.83) levels, along with further decreases in C3 (83.28±24.13) and C4 (17.48±4.86). Novelty: This study provides novel evidence of the immunological shifts in thalassemia patients post-splenectomy, demonstrating significant reductions in both immunoglobulins and complement proteins, thereby elevating the risk of infection. Implications: These findings highlight the spleen's crucial role in maintaining immune competence and suggest that splenectomy in thalassemia patients requires careful post-operative immune monitoring to mitigate infection risks. Highlights: Splenectomy lowers IgG, IgM, C3, and C4 levels in thalassemia patients. Post-splenectomy patients face higher infection risk due to immune weakening. Highlights spleen's crucial role in immune defense for thalassemia patients. Keywords: Thalassemia, Splenectomy, Immunoglobulins, Complement Proteins, Immune Competence

The Utility of Micro-R/Hypo-He Ratio Cut-off for Distinguishing Iron Deficiency Anemia and Minor Thalassemia

Thalassemia is a genetic disease with impaired synthesis of the globin chain that causes anemia. Thalassemia and Iron Deficiency Anemia (IDA) are both microcytic hypochromic anemia but have different proportions of hypochromic and microcytic erythrocytes due to differences in disease mechanisms. Research parameters of the hematology analyzer: %Micro-R, %Hypo-He, and MH ratio can be used as early screening for thalassemia and IDA. This study aimed to evaluate the cut-off of %Micro-R, %Hypo-He, and MH ratio to differentiate thalassemia from IDA. A cross-sectional study was carried out on 217 subjects. Subjects were divided into two groups, thalassemia and IDA based on hemoglobin electrophoresis, hematology examination, and Mentzer index. Differences and cut-off values of %Micro-R, %Hypo-He, and MH ratio between the two groups were analyzed. The number of collected data was 134, consisting of 89 thalassemia patients and 45 IDA patients. Thalassemia patients had a median %Micro-R value of 51.2 (4.3-79.0), %Hypo-He value of 7.2 (0.2-50.2), and MH ratio of 7.17 (1.10-64.50), higher than IDA patients (p=0.000; p=0.176; p=0.000). The optimal cut-off value for %Micro-R in discriminating thalassemia trait from IDA was &gt;12.7, with the area under the ROC curve (AUC) of 0.945, sensitivity of 92.1%, and specificity of 82.2%. The cut-off value for MH ratio &gt; 3.27 with AUC 0.833, sensitivity of 85.4%, and specificity 77.8% showed lower performance of cut-off value compared to %Micro-R. The algorithm using %Micro-R and MH ratio was proposed for thalassemia trait screening. High %Micro-R and MH are suggestive of thalassemia trait than of IDA.

A Practical Study on the Relationship between Serum Iron Elevation and Liver Enzymes Plus Other Factors in Patients with Beta-Thalassemia

Thalassemia is a genetic condition characterized by faulty hemoglobin synthesis and low hemoglobin concentration. Overload of iron is an unavoidable condition experienced by severe thalassemia patients as a result of excessive blood transfusions. We looked at impaired liver function in thalassemia individuals with Iraq as a result of these issues. Our findings demonstrated serum activity in hepatocytes, as well as a large rise in GOT and AIP in patients with elevated iron levels and a substantial rise in TSB. All of these elements may work together or independently to create chronic liver disease by causing damage in cells via oxidative mechanisms.

Profile Laboratory of Thalassemia in the General Hospital Dr. Zainoel Abidin Banda Aceh

Thalassemia refers to the globin gene abnormality that affects the a and b globin genes. A comprehensive peripheral blood laboratory examination, Mentzer index, blood morphology, and Hb analysis were all performed on every patient with thalassemia who attended treatment as part of this analytical observational study. This research aims to know the profile of laboratory examinations of thalassemia patients in the Dr. Zainoel Abidin General Hospital (RSUZA) Banda Aceh. The study's target population was 547 individuals, with 278 males and 269 females making up the male and female split, respectively (50.7% and 49.3%). With a total of 197 subjects (36.4%), this study revealed that the subjects were most frequently found in the age range of 0–5 years. Only 8 subjects, or 1.5%, of the population in the over-65 age group, were detected. The typical value of the erythrocyte index further fell and was discovered in 469 participants with a value of 85.3%. A total of 504 patients, or 91.6%, had more elevated RDW features. Results for the Mentzer index with 432 subjects were determined to be 13 were 78.5%. In the 450-subject hypochromic microcytic group, subjects were most frequently observed (81.8%). Blood morphology features from 505 participants, or 91.8% of the total, showed no additional blood morphology characteristics in normoblasts, and from 361 subjects, or 65.6% of the total, showed no target cells. When a person has anemia or a family history of thalassemia, it is strongly advised that they get a full blood count (CBC). The proper laboratory testing is still necessary for the health issue of thalassemia.

Case Report: Hemoglobin Hasharon with Concurrent Alpha Thalassemia in a Patient with Maple Syrup Urine Disease

Abstract Hemoglobin Hasharon (Hb Hasharon) is an unstable hemoglobin variant stemming from a mutation in the alpha globin gene. This mutation involves the replacement of aspartic acid with histidine at position 47 of the alpha globin chain. Initially identified in 1967 in Israel, Hb Hasharon has since been sporadically reported in various populations, including in Italy, Greece, Germany, and among Latin Americans of Mediterranean descent. Only three English articles have reported several cases of the combined alpha thalassemia deletion and Hasharon mutation, all between 1978-1980. Notably, there has been no prior report of Hb Hasharon with concurrent alpha thalassemia in patients with maple syrup urine disease (MSUD). We hereby present the first case of Hb Hasharon with alpha thalassemia in a patient diagnosed with MSUD. This patient, a 16-month-old female, received a prenatal diagnosis of MSUD through amniocentesis, confirming homozygosity for a known pathogenic variant in DBT (c.75_76delAT, p.C26wfsX2). Prompt initiation of formula feeding has effectively controlled her MSUD. The patient was referred for further evaluation due to hemoglobin newborn screen showing hemoglobin A, Hb F and “variant hemoglobin”. Her parents denied any family history of hemoglobinopathy. Her complete blood count was predominantly normal except for mild microcytosis, with a mean corpuscular volume of 69.1 fl (normal range 70.0-86.0 fl). The patient didn’t exhibit neonatal jaundice or any other signs or symptoms of hemolysis. The reticulocyte count was also within normal limits. The hemoglobin electrophoresis results revealed a complex pattern, with 28.8% of an unknown hemoglobin between zone 4 and 5 on capillary zone electrophoresis (CZE) as well as a possible A2 variant in zone 1. High-performance liquid chromatography (HPLC) indicated a 29.1% peak at a retention time of 4.72 minutes, along with several smaller peaks, that were indicative of the degradation of the unstable unknown hemoglobin. Although the zones and retention time aligned with Hb Hasharon, the percentage differed from the expected range of 19-20% in CZE and 18-21% in HPLC for this variant, prompting the team to order alpha and beta globin sequencing tests. Beta globin gene complete sequencing yielded negative results, while the sequencing of alpha globin gene revealed that the patient carries one copy of the -alpha3.7 alpha-globin deletion and one copy of the c.142G&amp;gt;C (p.Asp48His) variant in the alpha2-globin (HBA2) gene, resulting in an -alpha/alpha2alpha1 genotype with Hb Hasharon. While Hb Hasharon is generally not clinically significant, its co-occurrence with alpha-thalassemia can lead to hemolytic anemia. In our patient, clinic and chemical parameters were predominantly within normal ranges, except for mild microcytosis. The potential interaction between MSUD and Hb Hasharon with concurrent alpha thalassemia remains unknown. Continued patient monitoring will enable us to evaluate whether these conditions may influence each other’s clinical and biochemical profiles.

Plasma sphingomyelin levels were negatively correlated with ferritin levels in splenectomized thalassemia patients

Abstract Beta thalassemia results from decreased production of beta chains due to either mutations or deletions in the beta-globin gene, leading to impaired production of hemoglobin A. Thalassemia patients take frequent blood transfusions to compensate for hemolytic anemia and iron overload. Iron overload is monitored by serum ferritin levels in these patients. Extra-medullary hematopoiesis in beta thalassemia major leads to hypersplenism which often necessitates splenectomy to increase red cell life span and decrease transfusion need. Sphingomyelin is the second most abundant phospholipid in human plasma after phosphatidylcholine. In contrast to the well-defined roles of sphingolipids in cell membranes, their possible physiological role in lipoprotein metabolism has recently gained attention. Increased circulating levels of sphingomyelins and ceramides were observed in obesity, diabetes, and cardiovascular diseases. Although lipid abnormalities such as hypocholesterolemia and relatively increased triglycerides were reported in beta-thalassemia patients, there is no study investigating sphingolipid levels in thalassemia. Therefore, we investigate certain long chain and very long chain sphingomyelins and ceramides in beta-thalassemia patients who are under routine follow-up in our hospital. Thalassemia major patients who applied to the hospital for regular blood transfusion and gave consent were included in the study. Blood samples were obtained before transfusion. Plasma sphingomyelin (C16, C18 and C24) and ceramide (C16, C18, C20, C22, C24) species were measured by triple quadruple LC-ESI-MS/MS (Shimadzu, Japan). D-erythrosphingosine-D9 (Matreya) was used as an internal standard, all other lipid standards were from Avanti. Body iron stores of the patients were monitored by serum ferritin levels. A total of thirty patients were included in the study. All patients typically received regular erythrocyte suspension transfusions every three weeks and continuous oral iron chelation therapy. Twenty of the patients had a previous splenectomy. The mean age was 34.5 ±8.1 years in the splenectomy group and 32.8 ±8 years in the group without splenectomy. Mean ferritin levels were not different between the groups, being 1073.2±563.5 µg/L in splenectomy and 1709 ±1660.4 µg/L in non-splenectomy groups. All measured sphingolipid levels were similar between splenectomy and non-splenectomy groups. When correlation analysis was performed between measured sphingolipid and ferritin levels, significant negative correlations were found between sphingomyelin C16 (r= -0.591 p&amp;lt;0.006) and C18 (r= -0.594 p&amp;lt;0.006) with ferritin levels in the splenectomy group. However, this negative correlation was absent in the non-splenectomy group. In conclusion, we found that iron overload is associated with lower plasma sphingomyelin levels in splenectomized thalassemia patients. We have been working on the lipidomic analysis of the plasma and erythrocytes of thalassemia patients and other hemolytic anemias. The results may further help to get a better picture of lipid metabolism in thalassemia.

Differential gut microbiota composition in β-Thalassemia patients and its correlation with iron overload

Recent research highlights the significant impact of the gut microbiota on health and disease. Thalassemia, a hereditary blood disorder, requires regular blood transfusions, leading to an accumulation of iron in the body. Such changes could potentially alter the intestinal microbiota, thereby increasing the susceptibility of thalassemic patients to infection. In this study, we analyzed the fecal microbiota of 70 non-transfusion-dependent (NTDT) β-thalassemia/HbE patients and 30 healthy controls. Our findings indicate that iron chelation intervention had no detectable effect on the microbiome profile of thalassemic patients. However, the cross-sectional analysis revealed that the bacterial diversity and community structure in patients were significantly less diverse and distinct compared to those of healthy subjects. Using reference frames, we were also able to demonstrate that bacterial taxa that are known to produce short chain fatty acids, from the genera Alistipes, Coprococcus, and Oscillospira, and those from the family Ruminococcaceae, were less prevalent in the patients. In contrast, bacterial taxa associated with an unhealthy gut, including the genus Clostridium and those from the families Fusobacteriaceae, Enterobacteriaceae, and Peptostrptococcaceae, were more prevalent in patients and found to be correlated with higher levels of ferritin. Collectively, these changes in the microbiota could be regarded as markers of raised ferritin levels, and therefore, awareness should be exercised as they could interfere, albeit indirectly, with the treatment of the co-morbidities of thalassemia.

Organ-Specific Iron Overload in Non-Transfusion-Dependent Thalassemia Patients: Insights from Quantitative MRI Evaluation

ObjectiveTo elucidate the iron load in different organs of non-transfusion-dependent thalassemia (NTDT) patients using magnetic resonance imaging (MRI) T2* scan. MethodsThirty-four NTDT patients, including 28 NTDT iron chelation without and 6 NTDT with iron chelation, together with 15 normal controls, underwent MRI examination between December 2022 and July 2024 were enrolled in the study. Measured T2* of the pituitary gland, kidney cortex, heart, liver, pancreas, spleen. Liver and spleen volumes were evaluated. ResultsOf the 28 patients in NTDT without iron chelation group, 19 patients with iron overload in the liver, 9 patients with iron overload in the kidneys, and 4 patients with iron overload in the spleen. Most patients with abnormal kidney and spleen iron (76.9 %) had liver iron overload. Compared with the control group, NTDT without iron chelation patients had lower T2* in the liver, kidney, and spleen (p < 0.05). And heart T2* was correlated with kidney T2* (r = 0.480, p = 0.010) and pancreas (r = 0.411, p = 0.037). Liver T2* was correlated with spleen T2* (r = 0.479, p = 0.011). Pancreas T2* was correlated with pituitary T2* (r = -0.433, p = 0.031). ConclusionsNTDT patients exhibit significant organ-specific iron overload, particularly in the liver, kidneys, and spleen. The correlations between iron levels in different organs suggest interconnected mechanisms of iron accumulation. These findings highlight the importance of regular MRI screening to monitor and manage iron overload in NTDT patients.

7982 Is there a Connection between Alpha Thalassemia and Thyroid Disorders

Abstract Disclosure: W. Akhter: None. V. Taqi: None. J.L. Gilden: None. IntroductionA number of case reports suggest an association between thalassemia and autoimmune diseases through specific mutations and molecular pathways. An example is thyroid disease in thalassemia patients. Due to factors such as age, ethnicity and treatment protocol differences, the frequency of hypothyroidism in thalassemia patients is a wide range of 4 to 29% based on free T4 and TSH levels. Subclinical hypothyroidism is more common in thalassemia patients as compared to overt hypothyroidism. 90% of morbidity and mortality in B-Thalassemia patients is attributed to iron overload, anemia and hypoxia. Understanding this possible mechanism helps guide treatment and monitoring. Case PresentationWe present the case of a 26-year-old African American with Haitian ethnicity female, who upon routine testing was found to have a very high TSH level of 79.084 uIU/ml (nl=0.550-4.780 uIU/ml) for which 125 mcg of Levothyroxine was started, and then she was referred to the endocrine clinic. Past history was notable for sickle cell trait and alpha thalassemia trait. Patient stated that at age 12, she developed fatigue and low energy and was found to have hyperthyroidism which was treated with RAI ablation. After that, no follow up or lab tests were done until recently. The patient denied symptoms of hypo or hyperthyroidism or enlargement of the thyroid gland. She denied any family history of thyroid disorders. After presenting to the endocrine clinic a few days later, she was diagnosed with postprocedural hypothyroidism and the same dose of levothyroxine was continued. Physical exam was unremarkable and no thyromegaly was appreciated on exam. Labs were notable for decreased Hemoglobin of 11.4 g/dL (nl=12-16 g/dL) and CMP was unremarkable except low glucose of 65 mg/dL (nl=70-99 mg/dL). The patient’s most recent labs after 8 weeks of taking Levothyroxine were notable for TSH of 14.65 uIU/ml (nl=0.550-4.780 uIU/ml) and free T4 of 1 ng/dL (nl= 0.89-1.76 ng/dL) and the patient admitted to having still no thyroid symptoms and a little more energy. ConclusionEndocrinopathies are common complications of thalassemia with hypothyroidism being the second most common endocrine disorder in thalassemia patients after hypogonadism, reported in 5.6-17% of patients. In thalassemia patients, endocrine disorders have to be managed as early as possible. Therefore, it is recommended that an endocrine evaluation be carried out in thalassemia patients at a young age.Monitoring for glucose homeostasis, hypothyroidism and hypoparathyroidism is also warranted. Physicians caring for thalassemia patients should perform routine screening for and treat thyroid dysfunction appropriately. Reference: De Sanctis V, Soliman AT, Canatan, et al.. Thyroid Disorders in Homozygous β-Thalassemia: Mediterr J Hematol Infect Dis. 2019 May 1;11(1):e2019029. doi: 10.4084/MJHID.2019.029. PMID: 31205633; PMCID: PMC6548211. Presentation: 6/2/2024

Enhanced Gene Expression of Toll-Like Receptors 3, 7, and 9 in Thalassemia Patients: Implications for Inflammation and Potential Therapeutic Targets

Thalassemia is an inherited blood disorder marked by reduced hemoglobin synthesis, which leads to chronic anemia and systemic complications, among them immune dysregulation and chronic inflammation. The current study aims at investigating the gene expression of TLR3, 7, and 9 in thalassemia patients and their relation to the inflammatory markers. Because we used a larger, diverse sample population and a longitudinal study design, we were able to reveal significant upregulation of TLR3 and TLR9 in thalassemia patients compared to healthy controls strongly correlated with the high levels of various proinflammatory cytokines. We have further demonstrated that different genetic polymorphisms in the promoter regions of TLR3 and TLR9 alters the binding of transcription factors and thus can be possible causes of the dysregulation of these genes. Our results implicate that TLR3 and TLR9 themselves play a very important role in the inflammatory response in thalassemia and are therefore potential therapeutic targets for mitigating inflammation to improve outcomes in these patients.

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Combined effects of exercise and nutritional interventions on sarcopenia and its associated quality of life in transfusion-dependent thalassemia patients: a single-arm, open-label study

Analysis of Genetic Characteristics of Patients with Thalassemia in the Chengdu Region, Sichuan Province

To analyze the gene mutation types and composition characteristics of patients with thalassemia in Chengdu Region, Sichuan Province. 6 649 suspected thalassemia patients with positive screening results who visited Chengdu Women's and Children's Center Hospital from January 2017 to December 2020 were selected as the study subjects. Among them, there were 2 273 males and 4 376 females. The frequency and distribution of α and β genotypes of thalassemia in this cohort was analyzed by Luminex liquid-phase microarray method. Among the 6 649 samples, 3 787 were genetically diagnosed as thalassemia, with a total positive rate of 56.96%; in which, 2 063 (31.03%) cases were β-thalassemia, 1 629 (24.50%) cases were α-thalassemia, and 95 (1.43%) cases were α combined with β thalassemia. The types of β-thalassemia gene mutation were mainly CD17/N (36.45%, 752/2 063), CD41-42/N (25.30%, 522/2 063), and IVS-II-654/N (24.72%, 510/2 063); and 2 037 cases of simple heterozygous mutations were identified, accounting for 98.74% of β-thalassemia patients. The types of α-thalassemia gene mutation were mainly -- SEA/αα (79.01%, 1 287/1 629), -α3.7/αα (10.62%, 173/1 629), -α3.7/-- SEA (2.95%, 48/1 629), and -α4.2/αα (2.15%, 35/1 629). The α combined with β thalassemia was dominated by -α3.7/αα; CD17/N and -α3.7/αα; IVS-II-654/N, both accounting for 14.74% (14/95) of patients with α combined with β thalassemia. In Chengdu region, Sichuan province, β thalassemia is more common than α thalassemia, the main type of β thalassemia mutation is CD17/N, and the main type of α thalassemia mutation is -- SEA/αα, with regional characteristics.