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2 Common genotypes and basic classification of beta thalassemia

2 Common genotypes and basic classification of beta thalassemia

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Thalassemia and sickle cell disease (SCD) are disorders of hemoglobin that affect millions of people worldwide. The carrier states for these diseases arose as common, balanced polymorphisms during human history because they afforded protection against severe forms of malaria. These complex, multisystem diseases are reviewed here with a focus on cur...

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Citations

... Transgenic modeling has revealed that methyltransferases such as DNMT3A/B impact B-cell activation, plasmacytic differentiation, and humoral immunity. 10 Other contributors worthy of investigation include regulators of histone methylation such as KMT2A, KMT2D, and KDM6A that are frequently mutated in WM. 2 In summary, Roos-Weil and colleagues have added a third dimension to our understanding of WM genomics, complementing revelations in the transcriptome and genome of WM, and allowing us to demarcate WM based on a spectrum of lymphoplasmacytic differentiation (see figure). ...
... Common diagnostic methods in newborns and beyond are Hb separation techniques like isoelectric focusing, high-performance liquid chromatography, and capillary electrophoresis [23]. In this study, 65% (298/460) of the physicians reported that they had diagnostic difficulties that limited them to clinical diagnosis and biological confirmation only by a sickle cell test. ...
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Background: Sickle cell disease is a major public health issue in the Democratic Republic of Congo (DRC), but it is still poorly understood by health professionals. The objective of this study was to assess the knowledge and practices of Congolese physicians treating sickle cell disease (SCD), in order to identify the areas for improvement in clinical care. Methods: This was a descriptive observational study conducted among Congolese physicians using a questionnaire. Participants were evaluated using a pre-established answer grid. Results: A total of 460 physicians participated, including 81 women (18%), with an average age of 35 years (range 25-60 years). Most physicians were general practitioners. Although self-assessment of their level of knowledge on SCD was estimated as average to good, less than half of the participants (n = 460; 46%) reported adequate management of vaso-occlusive crises, and only 1% of them had received specific training on SCD. Most physicians reported difficulties both in terms of diagnostic (65%) and management (79%) options of SCD patients. This study also showed that 85% of these physicians did not have access to the diagnostic tools for SCD. Conclusions: Insufficient knowledge on SCD and poor diagnostic and treatment options might contribute to increased morbidity and mortality of patients living in the DRC. Interventions aiming to improve physicians' knowledge, patient follow-up, and treatment access are needed. Specific training alongside existing programs (HIV, malaria), early diagnosis of the disease, and the creation of patient advocacy groups should be implemented to improve SCD patient care.
... This can be evidenced through differential distribution of beta-thalassemic carrier gene frequency in different endogamous populations in India ranging from as low as 3% to as high as 17% [16]. Now, it is high time to deal with thalassemic carriers with microcytic anemia with a different strategy other than iron supplementation [17]. The absence of macrocytic anemia among β-thalassemia carriers suggests the survival disadvantage of β-thalassemia carriers with macrocytic anemia. ...
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Abstract: Hemoglobinopathy is a condition in which an individual carries an abnormal variant of hemoglobin gene and common genetic abnormalities in India. In heterozygous conditions particularly thalassemia trait is reported to be associated adverse phenotypes such as anemia, kidney problem, etc. The aim of the present study is to understand the status of anemia with special reference to β-thalassemia carriers. A total of 2969 individuals of both sexes in the age group of 13-30 years were recruited and screened for hemoglobinopathies, where 199 cases and same recruited cohort 199 age and sex matched controls. The hematological parameter levels were estimated by CBC and HPLC to confirm and distinguish between different hemoglobinopathies and thalassemia. The frequency of anemia was higher (74.4%) among cases as compared to that of the controls (31.2%). Microcytic anemia is significantly higher among cases (87.8%) whereas normocytic anemia is significantly higher among controls (66.1%). β-thalassemia carriers are found to be effected by anemia specifically microcytic anemia. The indices, RBC count and hematological parameters provided high consistencies for differentiating β-thalassemia carriers and anemia. Key words: Hemoglobinopathies, Thalassemia carriers, Microcytic Anemia, Mentzer Index, Srivastava Index
... Iron overload due to prolonged transfusion therapy and high gastrointestinal absorption due to ineffective erythropoiesis occurs in patients with thalassemia. As such, current recommendations are for children to begin treatment with an iron chelator [55]. ...
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Thalassemia syndromes are a group of inherited blood disorders caused by limitation or absence of alpha or beta- globin chain synthesis resulting in ineffective erythropoiesis and chronic hemolytic anemia. According to the clinical fact of thalassemia as recessive autosomal, thalassemia divided into alpha and beta thalassemia. The main complication of beta thalassemia is excessive red blood cells destruction, oxidative stress, extramedullary hematopoiesis pseudotumors, hemosiderosis-induced organ dysfunction, malignancy, polyneuropathy, myopathy, osteoporosis, and leg ulcers. Although, the first obligatory therapy for thalassemia major is a blood transfusion, cause cardiac and hepatic hemosiderosis that is the most common cause of death in these patients. The targeted sequencing protocols include Hb F inducers, ineffective erythropoiesis correctors, antioxidant, vitamins, and herbals. Resveratrol is a novel herbal therapeutic approach for β-thalassemia. New appearance of molecular therapy in response to adverse effects of drugs. ActRIIB/IgG1 Fc recombinant protein is a novel molecular therapy in thalassemia. This review focuses light on maximizing the efficacy of unique combinations and new future therapeutic interventions in thalassemia that reverse splenomegaly, reduce transfusion frequency, decrease iron toxicity in organs and correct the chronic anemia. Hematopoietic stem cells transplantation (HSCT) is the only new curative therapy for hemoglobinopathies in gene therapy for thalassemia major and preferred more than iron chelation and blood transfusion for ensuring long life of these patients. New development in gene addition strategies by lentiviral vectors and LentiGlobin BB305. Novel advanced approaches target to cut DNA at a targeted site and convert of HbF to HbA during infancy by gene editings such as BCL11A (B cell lymphoma11A) suppression, HPFH (hereditary persistence of fetal hemoglobin) and Zinc-Finger Nucleases.
... Beta-thalassemia usually results from point mutations in globin genes located on the short arm of chromosome 11 [8,10,13]. The clinical severity is also a function of the number and type of genetic defects, ranging from less severe forms such as beta thalassemia trait which is asymptomatic and characterized by mild microcytic, hypochromic anaemia, to more severe forms like beta thalassemia major in which patients suffer from severe anaemia from infancy. ...