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Minerva Pediatrics Jun 2022Beta-thalassemia is a potentially lethal hereditary anemia, caused by reduced or absent expression of HBB polypeptide chains of adult hemoglobin (HbA: α2β2). Current... (Review)
Review
Beta-thalassemia is a potentially lethal hereditary anemia, caused by reduced or absent expression of HBB polypeptide chains of adult hemoglobin (HbA: α2β2). Current curative treatments options are limited to few patients, while alternative, chronic palliative therapy consisting of frequent transfusions coupled with iron chelation therapy, are costly. The above treatments also affect quality of life of patients. A search was conducted in the electronic databases like Medline, PubMed, etc. for screening studies reporting various aspects including gene therapy, prevention strategies, blood, transfusion and chelation therapy for the management of β-thalassemia. Increased levels of fetal hemoglobin (HbF: α2γ2) were shown to lessen the severity of β-thalassemia, highlighting the therapeutic potential of a gene-therapy-mediated increase in HBG1 and HBG2 (HBG) expression. The primary outcome of most of the above studies was the efficient management of β-thalassemia, without any major complication. So, the present review is focused on the recent perspectives in the management of β-thalassemia including combinatorial gene therapy for β-thalassemia.
Topics: Adult; Chelation Therapy; Child; Fetal Hemoglobin; Hemoglobin A; Humans; Quality of Life; beta-Thalassemia
PubMed: 29479942
DOI: 10.23736/S2724-5276.18.04872-7 -
International Journal of Molecular... Sep 2022Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes β-TI hemoglobin,... (Review)
Review
Thalassemia is the most common genetic disorder worldwide. Thalassemia intermedia (TI) is non-transfusion-dependent thalassemia (NTDT), which includes β-TI hemoglobin, E/β-thalassemia and hemoglobin H (HbH) disease. Due to the availability of iron chelation therapy, the life expectancy of thalassemia major (TM) patients is now close to that of TI patients. Iron overload is noted in TI due to the increasing iron absorption from the intestine. Questions are raised regarding the relationship between iron chelation therapy and decreased patient morbidity/mortality, as well as the starting threshold for chelation therapy. Searching all the available articles up to 12 August 2022, iron-chelation-related TI was reviewed. In addition to splenectomized patients, osteoporosis was the most common morbidity among TI cases. Most study designs related to ferritin level and morbidities were cross-sectional and most were from the same Italian study groups. Intervention studies of iron chelation therapy included a subgroup of TI that required regular transfusion. Liver iron concentration (LIC) ≥ 5 mg/g/dw measured by MRI and ferritin level > 300 ng/mL were suggested as indicators to start iron chelation therapy, and iron chelation therapy was suggested to be stopped at a ferritin level ≤ 300 ng/mL. No studies showed improved overall survival rates by iron chelation therapy. TI morbidities and mortalities cannot be explained by iron overload alone. Hypoxemia and hemolysis may play a role. Head-to-head studies comparing different treatment methods, including hydroxyurea, fetal hemoglobin-inducing agents, hypertransfusion as well as iron chelation therapy are needed for TI, hopefully separating β-TI and HbH disease. In addition, the target hemoglobin level should be determined for β-TI and HbH disease.
Topics: Ferritins; Humans; Iron; Iron Chelating Agents; Iron Overload; alpha-Thalassemia; beta-Thalassemia
PubMed: 36077584
DOI: 10.3390/ijms231710189 -
Medical Hypotheses Sep 2020The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the... (Observational Study)
Observational Study
The novel coronavirus pneumonia (COVID-19) is a contagious acute respiratory infectious disease whose causative agent has been demonstrated to be a novel virus of the coronavirus family, SARSCoV-2. A recent PRE-print study has showed a heme attack on the 1-beta chain of hemoglobin by COVID19. Beta-thalassemia results of a default in the hemoglobin beta-chain synthesis. 1,5% global population are heterozygotes for this disease. In this study, by a multiple linear regression, we have analyzed the evolution of COVID-19 infection in three Italian regions (Puglia, Sardinia, Sicilia) with different beta-thalassemic prevalences, in order to search a link. The results have showed that betathalassemic heterozygote population prevalence is correlated to immunity against COVID-19, by a regression. This paper is only for academic discussion, the hypotheses and conclusions needs to be confirmed by further research.
Topics: Betacoronavirus; COVID-19; Coronavirus Infections; Female; Hemoglobins; Heterozygote; Humans; Immune System; Immunization; Italy; Male; Middle Aged; Pandemics; Pneumonia, Viral; Prevalence; Regression Analysis; SARS-CoV-2; Treatment Outcome; beta-Thalassemia
PubMed: 32447232
DOI: 10.1016/j.mehy.2020.109827 -
Acta Bio-medica : Atenei Parmensis Sep 2021Starting from 2021, Acta Biomedica Parmensis will dedicate an annual update to the "Advances in Hemoglobinopathies". The section editor of this new editorial initiative...
Starting from 2021, Acta Biomedica Parmensis will dedicate an annual update to the "Advances in Hemoglobinopathies". The section editor of this new editorial initiative is prof. Ashraf T Soliman, Pediatrician and Endocrinologist at Hamad Medical Center (HMC) of Doha. Prof Soliman is a pionier in the study of endocrine complications in hemoglobinopathies and effects of blood transfusions on spermatogenesis. He collaborates strictly with prof. Mohamed Yassin, Hematologist-Oncologist at MCH and the International Network of Clinicians for Endocrinopathies in Thalassemia and Adolescence Medicine (ICET-A). This issue of Acta Biomedica contains three articles on: The different patterns of insulin response during Oral Glucose Tolerance Test (OGTT) in transfused young patients with β- Thalassemia; Immigration and screening programs for hemoglobinopathies in Italy, Spain and Turkey and The effects of treatment with blood transfusion, iron chelation and hydroxyurea on puberty, growth and spermatogenesis in sickle cell disease,.
Topics: Anemia, Sickle Cell; Emigration and Immigration; Hemoglobinopathies; Humans; Male; Thalassemia; beta-Thalassemia
PubMed: 34487058
DOI: 10.23750/abm.v92i4.11927 -
International Journal of Molecular... Nov 2023Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ... (Review)
Review
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ damage observed mainly in patients with β-thalassemia and rarely in SCD. Iron overload, oxidative stress-induced cellular damage, chronic anemia, and HCV infection contribute to the development of endocrinopathies in β-thalassemia. The above factors, combined with vaso-occlusive events and microcirculation defects, are crucial for endocrine dysfunction in SCD patients. These endocrinopathies include diabetes mellitus, hypothyroidism, parathyroid dysfunction, gonadal and growth failure, osteoporosis, and adrenal insufficiency, affecting the quality of life of these patients. Thus, we aim to provide current knowledge and data about the epidemiology, pathogenesis, diagnosis, and management of endocrine disorders in β-thalassemia and SCD. We conducted a comprehensive review of the literature and examined the available data, mostly using the PubMed and Medline search engines for original articles. In the era of precision medicine, more studies investigating the potential role of genetic modifiers in the development of endocrinopathies in hemoglobinopathies are essential.
Topics: Humans; Iron; beta-Thalassemia; Quality of Life; Hemoglobinopathies; Anemia, Sickle Cell; Diabetes Mellitus
PubMed: 38003451
DOI: 10.3390/ijms242216263 -
Drug Discovery Today Nov 2022In many countries, β-thalassemia (β-THAL) is not uncommon; however, it qualifies as a rare disease in the US and in European Union (EU), where thalassemia drugs are... (Review)
Review
In many countries, β-thalassemia (β-THAL) is not uncommon; however, it qualifies as a rare disease in the US and in European Union (EU), where thalassemia drugs are eligible for Orphan Drug Designation (ODD). In this paper, we evaluate all 28 ODDs for β-THAL granted since 2001 in the US and the EU: of these, ten have since been discontinued, twelve are pending, and six have become licensed drugs available for clinical use. The prime mover for these advances has been the increasing depth of understanding of the pathophysiology of β-THAL; at the same time, and even though only one-fifth of β-THAL ODDs have become licensed drugs, the ODD legislation has clearly contributed substantially to the development of improved treatments for β-THAL.
Topics: Humans; Orphan Drug Production; beta-Thalassemia; Rare Diseases; Legislation, Drug; European Union
PubMed: 36058507
DOI: 10.1016/j.drudis.2022.103342 -
Scientific Reports May 2021β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease... (Observational Study)
Observational Study
β-Thalassemia/HbE disease has a wide spectrum of clinical phenotypes ranging from asymptomatic to dependent on regular blood transfusions. Ability to predict disease severity is helpful for clinical management and treatment decision making. A thalassemia severity score has been developed from Mediterranean β-thalassemia patients. However, different ethnic groups may have different allele frequency and linkage disequilibrium structures. Here, Thai β-thalassemia/HbE disease genome-wild association studies (GWAS) data of 487 patients were analyzed by SNP interaction prioritization algorithm, interacting Loci (iLoci), to find predictive SNPs for disease severity. Three SNPs from two SNP interaction pairs associated with disease severity were identifies. The three-SNP disease severity risk score composed of rs766432 in BCL11A, rs9399137 in HBS1L-MYB and rs72872548 in HBE1 showed more than 85% specificity and 75% accuracy. The three-SNP predictive score was then validated in two independent cohorts of Thai and Malaysian β-thalassemia/HbE patients with comparable specificity and accuracy. The SNP risk score could be used for prediction of clinical severity for Southeast Asia β-thalassemia/HbE population.
Topics: Adolescent; Adult; Asian People; Child; Child, Preschool; Cohort Studies; Female; GTP-Binding Proteins; Gene Frequency; Genome-Wide Association Study; Hemoglobin E; Humans; Infant; Infant, Newborn; Linkage Disequilibrium; Malaysia; Male; Polymorphism, Single Nucleotide; Proto-Oncogene Proteins c-myb; Repressor Proteins; Sensitivity and Specificity; Severity of Illness Index; Thailand; Young Adult; beta-Thalassemia
PubMed: 33990643
DOI: 10.1038/s41598-021-89641-2 -
British Journal of Clinical Pharmacology Aug 2022Beta-thalassaemia, including sickle cell anaemia and thalassaemia E, is most common in developing countries in tropical and subtropic regions. Because carriers have... (Review)
Review
Beta-thalassaemia, including sickle cell anaemia and thalassaemia E, is most common in developing countries in tropical and subtropic regions. Because carriers have migrated there owing to demographic migration, β-thalassaemia can now be detected in areas other than malaria-endemic areas. Every year, an estimated 300 000-500 000 infants, the vast majority of whom are from developing countries, are born with a severe haemoglobin anomaly. Currently, some basic techniques, which include iron chelation therapy, hydroxyurea, blood transfusion, splenectomy and haematopoietic stem cell transplantation, are being used to manage thalassaemia patients. Despite being the backbone of treatment, traditional techniques have several drawbacks and limitations. Ineffective erythropoiesis, correction of globin chain imbalance and adjustment of iron metabolism are some of the innovative treatment methods that have been developed in the care of thalassaemia patients in recent years. Moreover, regulating the expression of B-cell lymphoma/leukaemia 11A and sex-determining region Y-box through the enhanced expression of micro RNAs can also be considered putative targets for managing haemoglobinopathies. This review focuses on the biological basis of β-globin gene production, the pathophysiology of β-thalassaemia and the treatment options that have recently been introduced.
Topics: Blood Transfusion; Humans; Infant; Iron; Iron Chelating Agents; Thalassemia; beta-Thalassemia
PubMed: 35373382
DOI: 10.1111/bcp.15343 -
International Journal of Molecular... Sep 2021Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain... (Review)
Review
Thalassemia, a chronic disease with chronic anemia, is caused by mutations in the β-globin gene, leading to reduced levels or complete deficiency of β-globin chain synthesis. Patients with β-thalassemia display variable clinical severity which ranges from asymptomatic features to severe transfusion-dependent anemia and complications in multiple organs. They not only are at increased risk of blood-borne infections resulting from multiple transfusions, but they also show enhanced susceptibility to infections as a consequence of coexistent immune deficiency. Enhanced susceptibility to infections in β-thalassemia patients is associated with the interplay of several complex biological processes. β-thalassemia-related abnormalities of the innate immune system include decreased levels of complement, properdin, and lysozyme, reduced absorption and phagocytic ability of polymorphonuclear neutrophils, disturbed chemotaxis, and altered intracellular metabolism processes. According to available literature data, immunological abnormalities observed in patients with thalassemia can be caused by both the disease itself as well as therapies. The most important factors promoting such alterations involve iron overload, phenotypical and functional abnormalities of immune system cells resulting from chronic inflammation oxidative stress, multiple blood transfusion, iron chelation therapy, and splenectomy. Unravelling the mechanisms underlying immune deficiency in β-thalassemia patients may enable the designing of appropriate therapies for this group of patients.
Topics: Adaptive Immunity; Biomarkers; Disease Susceptibility; Genetic Predisposition to Disease; Humans; Immune System; Immunity, Innate; beta-Thalassemia
PubMed: 34575839
DOI: 10.3390/ijms22189677 -
Human Genomics Jun 2021For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms... (Review)
Review
For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms of effectiveness and safety. So far, the most prevalent and promising treatment options for patients with β-types hemoglobinopathies, among others, predominantly include drug treatment and gene therapy. Despite the significant improvements of such interventions to the patient's quality of life, a variable response has been demonstrated among different groups of patients and populations. This is essentially due to the complexity of the disease and other genetic factors. In recent years, a more in-depth understanding of the molecular basis of the β-type hemoglobinopathies has led to significant upgrades to the current technologies, as well as the addition of new ones attempting to elucidate these barriers. Therefore, the purpose of this article is to shed light on pharmacogenomics, gene addition, and genome editing technologies, and consequently, their potential use as direct and indirect genome-based interventions, in different strategies, referring to drug and gene therapy. Furthermore, all the latest progress, updates, and scientific achievements for patients with β-type hemoglobinopathies will be described in detail.
Topics: Anemia, Sickle Cell; Gene Editing; Genetic Therapy; Hemoglobinopathies; Humans; beta-Globins; beta-Thalassemia
PubMed: 34090531
DOI: 10.1186/s40246-021-00329-0