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Journal of Clinical Laboratory Analysis Mar 2022Hainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study...
BACKGROUND
Hainan has one of the high incidences of thalassemia in China, but the epidemiological data in the whole province has not been reported yet. The objective of our study was to reveal the true prevalence and molecular mutation spectrum of thalassemia in the population of Hainan who are of childbearing age.
METHODS
We screened 166,936 individuals from 19 cities and counties in Hainan by hematological parameters analysis, and further conducted genetic analysis for individuals whose MCV was less than 82fL.
RESULTS
In total, 21,619 (12.95%) subjects were diagnosed as thalassemia carriers or patients. The overall prevalence of α-thalassemia, β-thalassemia, and α+β-thalassemia were 10.39%, 1.38%, and 1.18%, respectively. Eleven α-thalassemia mutations and sixteen β-thalassemia mutations were identified. The high-frequent genotypes of α-thalassemia were -α /αα (19.70%), -α /αα (19.39%), αα/-- (15.60%), α α/αα (9.24%), and -α /-α (8.90%), and those of β-thalassemia were β /β (58.92%), β /β (16.05%), β /β (8.42%), β /β (6.03%), β /β (5.47%), and β /β (2.69%). In addition, the frequencies and hematological profiles of many rare mutations of α- [Fusion, HKαα, αααanti , IVS-II-55 (T>G), IVS-II-119 (-G,+CTCGGCCC)] and β-globin genes [-50 (G>A), IVS-Ⅱ-81 (C>T)] in Hainan were reported for the first time.
CONCLUSION
Our study revealed the high prevalence and extensive molecular spectrum of thalassemia in childbearing age population of Hainan, suggesting thalassemia in Hainan ranks second in prevalence among all regions in China. The findings will be useful for genetic counseling and prevention of thalassemia.
Topics: China; Genotype; Heterozygote; Humans; Mutation; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 35119136
DOI: 10.1002/jcla.24260 -
BMC Pediatrics Apr 2024β-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This... (Observational Study)
Observational Study
BACKGROUND
β-Thalassemia major (BTM) is one of the most common hereditary anemias worldwide. Patients suffer from iron overload that results from repeated blood transfusion This in turn leads to multiple organ damage and endocrinopathies. This study aims to assess the prevalence of growth retardation, hypothyroidism, and diabetes mellitus in children and adolescents with BTM treated at Dubai Thalassemia Centre.
METHODS
A total of 105 children and adolescents were included in this retrospective observational study.
RESULTS
39 children and 66 adolescents' data were analyzed. Females composed 51.3% (n = 20) of children and 53.0% (n = 35) of adolescents. Pretransfusion hemoglobin below 9 gm/dl was observed in 10.8% (n = 4) and 10.6% (n = 7) in children and adolescents, respectively. The mean age of menarche was 13.5 years. Among all study participants, 22.6% (n = 14) had normal height velocity whereas 37.1% (n = 23) had reduced height velocity in one year and 40.3% (n = 25) had reduced height velocity in two consecutive years. The proportion of children and adolescents showing reduced height velocity was significantly higher in females compared to the males (90.6% versus 63.3%, respectively, Chi-square = 6.597, p-value = 0.010). Although none of the study participants had diabetes mellitus, 26.1% (n = 12/46) had pre-diabetes. Elevated TSH was observed in 14.7% (n = 5) children and 8.1% (n = 5) adolescents while low FT4 was reported in one child and one adolescent.
CONCLUSION
Of all endocrinopathies seen among children and adolescents with BTM, growth delay remains the main concern for this group of patients. Effective treatment is key to further reducing endocrinopathies. Although the sample size is limited, we postulate that the low percentage of endocrinopathies among children with BTM treated at Dubai thalassemia center and the low level of pretransfusion anemia reflect the effective transfusion and chelation at the center.
Topics: Male; Child; Female; Adolescent; Humans; beta-Thalassemia; Iron Chelating Agents; Iron Overload; Hypothyroidism; Diabetes Mellitus
PubMed: 38580952
DOI: 10.1186/s12887-024-04670-w -
Haematologica Apr 2015β-thalassemias are monogenic disorders characterized by defective synthesis of the β-globin chain, one of the major components of adult hemoglobin. A large number of... (Review)
Review
β-thalassemias are monogenic disorders characterized by defective synthesis of the β-globin chain, one of the major components of adult hemoglobin. A large number of mutations in the β-globin gene or its regulatory elements have been associated with β-thalassemias. Due to the complexity of the regulation of the β-globin gene and the role of red cells in many physiological processes, patients can manifest a large spectrum of phenotypes, and clinical requirements vary from patient to patient. It is important to consider the major differences in the light of potential novel therapeutics. This review summarizes the main discoveries and mechanisms associated with the synthesis of β-globin and abnormal erythropoiesis, as well as current and novel therapies.
Topics: Animals; Erythropoiesis; Humans; Iron; Phenotype; Therapies, Investigational; beta-Globins; beta-Thalassemia
PubMed: 25828088
DOI: 10.3324/haematol.2014.114827 -
Transfusion Oct 2021
Review
Topics: Blood Transfusion; Disease Management; Humans; United States; beta-Thalassemia
PubMed: 34453453
DOI: 10.1111/trf.16640 -
Hellenic Journal of Cardiology : HJC =... 2021Beta-thalassaemia is a genetic disease with different clinical aspects, which can lead to heart failure with a multifactorial mechanism. Over the last years, growing... (Review)
Review
Beta-thalassaemia is a genetic disease with different clinical aspects, which can lead to heart failure with a multifactorial mechanism. Over the last years, growing interest has been reported for biomarkers that may help in the diagnosis, staging and prognosis of heart disease at an early stage, in patients with beta-thalassaemia. This review will highlight the current clinical value of cardiac biomarkers in patients with beta-thalassaemia and the ongoing research for a possible expanded future use.
Topics: Biomarkers; Heart Failure; Humans; Prognosis; Thalassemia; beta-Thalassemia
PubMed: 32387594
DOI: 10.1016/j.hjc.2020.04.012 -
Journal of Medicine and Life Nov 2022This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to...
This study was conducted to assess the level of proteins C and S in patients with thalassemia intermedia from the Thalassemia Center in Erbil, Iraq. This study aimed to evaluate protein C and S levels in patients with β-thalassemia intermedia and correlate them to different clinical and laboratory parameters. This comprehensive descriptive case-control study was conducted in 2021. Twenty-three thalassemia intermedia patients were recruited. After the participants' demographic data were recorded, plasma levels of both proteins were measured. The acquired files were examined for the 23 patients studied, 48% of whom were female. The mean age of the patients was 16.32 years. The findings show that the proportion of protein C in males was greater than in females, while this percentage contrasts when compared with protein S (ranging between 89-99% and 85-96%, respectively). Concerning age, these two types of protein in children have more value compared to older ages. Only seven people had less than 1,000 ferritins, while the others had higher values. A decrease in proteins C and S was observed in the thalassemia intermediate compared to the control group. There was a significant relationship between the decreased protein C and S levels with splenectomy. Given the significant reduction in protein C and S levels among patients with thalassemia intermediate compared to the control group, there is an increased risk of thromboembolic events in patients with thalassemia intermediate.
Topics: Adolescent; Child; Female; Humans; Male; beta-Thalassemia; Case-Control Studies; Ferritins; Protein C; Protein S; Thromboembolism
PubMed: 36567848
DOI: 10.25122/jml-2021-0316 -
International Journal of Molecular... Jul 2021β-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of... (Review)
Review
β-thalassaemia is a rare genetic condition caused by mutations in the β-globin gene that result in severe iron-loading anaemia, maintained by a detrimental state of ineffective erythropoiesis (IE). The role of multiple mechanisms involved in the pathophysiology of the disease has been recently unravelled. The unbalanced production of α-globin is a major source of oxidative stress and membrane damage in red blood cells (RBC). In addition, IE is tightly linked to iron metabolism dysregulation, and the relevance of new players of this pathway, i.e., hepcidin, erythroferrone, matriptase-2, among others, has emerged. Advances have been made in understanding the balance between proliferation and maturation of erythroid precursors and the role of specific factors in this process, such as members of the TGF-β superfamily, and their downstream effectors, or the transcription factor GATA1. The increasing understanding of IE allowed for the development of a broad set of potential therapeutic options beyond the current standard of care. Many candidates of disease-modifying drugs are currently under clinical investigation, targeting the regulation of iron metabolism, the production of foetal haemoglobin, the maturation process, or the energetic balance and membrane stability of RBC. Overall, they provide tools and evidence for multiple and synergistic approaches that are effectively moving clinical research in β-thalassaemia from bench to bedside.
Topics: Activin Receptors, Type II; Drug Development; Erythropoiesis; GATA1 Transcription Factor; Hepcidins; Humans; Immunoglobulin Fc Fragments; Iron; Models, Biological; Mutation; Piperazines; Quinolines; Recombinant Fusion Proteins; Transforming Growth Factor beta; beta-Globins; beta-Thalassemia
PubMed: 34281283
DOI: 10.3390/ijms22137229 -
BioMed Research International 2019Endocrinopathies are common in patients with -thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Endocrinopathies are common in patients with -thalassemia major despite parenteral iron chelation therapy with deferoxamine. Prevalence of abnormal glucose metabolism in previous studies was controversial. The aim of this study was to discuss the prevalence of abnormal glucose metabolism in -thalassemia major based on a meta-analysis.
METHODS
PubMed, ScienceDirect, Springerlink, Ovid, Web of Science, MEDLINE, Wanfang database, and Chinese National Knowledge Internet were searched for relevant articles. Two authors selected the articles according to the inclusion criteria and then extracted the data. The prevalence of diabetes mellitus (DM) in -thalassemia major was defined as the primary outcome. The prevalence with the 95% confidence interval (95%CI) was used to evaluate the proportion of abnormal glucose metabolism and other endocrine disorders in patients with -thalassemia major. Subgroup analyses were applied to explore the prevalence in different regions. Sensitivity analysis and publication bias assessment were also conducted.
RESULTS
A total of 44 studies with 16605 cases were included in this analysis. Diabetes mellitus was present in 6.54% (95% CI: 5.30%-7.78%). The fixed subgroup study revealed that the region with the highest prevalence was the Middle East (prevalence= 7.90%, 95% CI: 5.75%-10.05%). The accumulated meta-analysis revealed that the prevalence of DM in -thalassemia major was relatively steady in each year. The prevalence of impaired fasting glucose (IFG), impaired glucose tolerance (IGT), and other endocrine disorders in -thalassemia major was 17.21% (95% CI: 8.43%-26.00%), 12.46% (95% CI: 5.98%-18.94%), and 43.92% (95% CI: 37.94%-49.89%), respectively. Sensitivity analysis showed that the pooled results were robust; publication bias assessment revealed that there was no significant evidence that the pooled results were influenced by publication bias.
CONCLUSION
High prevalence of endocrine disorders involving abnormal glucose metabolism was detected in -thalassemia major. Treatment and prevention measurements may be necessary to prevent growth and endocrine problems.
Topics: Chelation Therapy; Deferoxamine; Diabetes Mellitus; Endocrine System Diseases; Glucose; Glucose Intolerance; Humans; Iron Chelating Agents; Middle East; beta-Thalassemia
PubMed: 31119181
DOI: 10.1155/2019/6573497 -
Scientific Reports Nov 2022β-Thalassaemia results from defects in β-globin chain production, leading to ineffective erythropoiesis and subsequently to severe anaemia and other complications....
β-Thalassaemia results from defects in β-globin chain production, leading to ineffective erythropoiesis and subsequently to severe anaemia and other complications. Apoptosis and autophagy are the main pathways that regulate the balance between cell survival and cell death in response to diverse cellular stresses. Herein, the death of erythroid lineage cells in the bone marrow from both β-thalassaemic mice and β-thalassaemia/HbE patients was investigated. Phosphatidylserine (PS)-bearing basophilic erythroblasts and polychromatophilic erythroblasts were significantly increased in β-thalassaemia as compared to controls. However, the activation of caspase 8, caspase 9 and caspase 3 was minimal and not different from control in both murine and human thalassaemic erythroblasts. Interestingly, bone marrow erythroblasts from both β-thalassaemic mice and β-thalassaemia/HbE patients had significantly increased autophagy as shown by increased autophagosomes and increased co-localization between LC3 and LAMP-1. Inhibition of autophagy by chloroquine caused significantly increased erythroblast apoptosis. We have demonstrated increased autophagy which led to minimal apoptosis in β-thalassaemic erythroblasts. However, increased PS exposure occurring through other mechanisms in thalassaemic erythroblasts might cause rapid phagocytic removal by macrophages and consequently ineffective erythropoiesis in β-thalassaemia.
Topics: Humans; Mice; Animals; Erythropoiesis; beta-Thalassemia; Erythroblasts; Autophagy; Apoptosis
PubMed: 36329049
DOI: 10.1038/s41598-022-21249-6 -
Blood Jan 2019β-Thalassemia (BT) is an inherited genetic disorder that is characterized by ineffective erythropoiesis (IE), leading to anemia and abnormal iron metabolism. IE is an... (Review)
Review
β-Thalassemia (BT) is an inherited genetic disorder that is characterized by ineffective erythropoiesis (IE), leading to anemia and abnormal iron metabolism. IE is an abnormal expansion of the number of erythroid progenitor cells with unproductive synthesis of enucleated erythrocytes, leading to anemia and hypoxia. Anemic patients affected by BT suffer from iron overload, even in the absence of chronic blood transfusion, suggesting the presence of ≥1 erythroid factor with the ability to modulate iron metabolism and dietary iron absorption. Recent studies suggest that decreased erythroid cell differentiation and survival also contribute to IE, aggravating the anemia in BT. Furthermore, hypoxia can also affect and increase iron absorption. Understanding the relationship between iron metabolism and IE could provide important insights into the BT condition and help to develop novel treatments. In fact, genetic or pharmacological manipulations of iron metabolism or erythroid cell differentiation and survival have been shown to improve IE, iron overload, and anemia in animal models of BT. Based on those findings, new therapeutic approaches and drugs have been proposed; clinical trials are underway that have the potential to improve erythrocyte production, as well as to reduce the iron overload and organ toxicity in BT and in other disorders characterized by IE.
Topics: Animals; Erythropoiesis; Humans; Iron; Iron Metabolism Disorders; beta-Thalassemia
PubMed: 30401707
DOI: 10.1182/blood-2018-07-815928