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JPMA. the Journal of the Pakistan... Jan 2021Beta thalassemia in Pakistan is a serious health concern with an estimated 5-8% carrier frequency and birth of 5000 major children every year in the country. The... (Review)
Review
Beta thalassemia in Pakistan is a serious health concern with an estimated 5-8% carrier frequency and birth of 5000 major children every year in the country. The treatment of beta thalassemia major patients poses a great economic burden; hence, the ideal approach towards this disease should encompass effective prevention services. At present only one government funded project "Punjab Thalassemia Prevention Programme" existed in Punjab province, and providing free of cost services for beta thalassemia screening and prenatal diagnosis. Complete blood count and haemoglobin electrophoresis remains the preliminary test for screening, while chorionic villi sampling and amplification refractory mutation system method have been most widely used for molecular diagnosis of beta thalassemia. Modern molecular techniques, non-invasive prenatal diagnosis, and pre-implantation diagnosis are in trial phases. In this review we have discussed the available diagnostic facilities and status of prevention programmes for beta thalassemia in Pakistan as well as future perspectives.
Topics: Child; Chorionic Villi Sampling; Female; Humans; Pakistan; Pregnancy; Prenatal Diagnosis; Thalassemia; beta-Thalassemia
PubMed: 35157672
DOI: 10.47391/JPMA.665 -
Annals of the New York Academy of... Aug 2010Iron overload is the principal cause of morbidity and mortality in beta-thalassemia with or without transfusion dependence. Iron homeostasis is regulated by the hepatic...
Iron overload is the principal cause of morbidity and mortality in beta-thalassemia with or without transfusion dependence. Iron homeostasis is regulated by the hepatic peptide hormone hepcidin. Hepcidin controls dietary iron absorption, plasma iron concentrations, and tissue iron distribution. A deficiency in this hormone is the main or contributing factor of iron overload in iron-loading anemias such as beta-thalassemia. Hepcidin deficiency results from a strong suppressive effect of the high erythropoietic activity on hepcidin expression. Although in thalassemia major patients iron absorption contributes less to the total iron load than transfusions, in non-transfused thalassemia, low hepcidin, and the consequent hyperabsorption of dietary iron is the major cause of systemic iron overload. Hepcidin diagnostics and future therapeutic agonists may help in management of patients with beta-thalassemia.
Topics: Antimicrobial Cationic Peptides; Hepcidins; Homeostasis; Humans; Iron Overload; Iron, Dietary; beta-Thalassemia
PubMed: 20712769
DOI: 10.1111/j.1749-6632.2010.05585.x -
Blood Jul 2013In this issue of Blood, Pasricha et al evaluated serum hepcidin and its putative pathological suppressor growth differentiation factor-15 (GDF-15) in patients with...
In this issue of Blood, Pasricha et al evaluated serum hepcidin and its putative pathological suppressor growth differentiation factor-15 (GDF-15) in patients with β-thalassemia major before and after transfusion, in the context of erythropoietic activity and iron loading. The study offers insight into dynamic regulation of hepcidin in this disease, reinforces the likely contribution of hepcidin to iron loading between transfusions, and highlights the potential clinical utility of hepcidin measurements in the management of patients with β-thalassemia major.
Topics: Antimicrobial Cationic Peptides; Blood Transfusion; Erythropoiesis; Female; Hepcidins; Humans; Male; beta-Thalassemia
PubMed: 23828883
DOI: 10.1182/blood-2013-05-502617 -
Cold Spring Harbor Perspectives in... Jul 2012Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β-thalassemia intermedia has substantially... (Review)
Review
Our understanding of the molecular and pathophysiological mechanisms underlying the disease process in patients with β-thalassemia intermedia has substantially increased over the past decade. Earlier studies observed that patients with β-thalassemia intermedia experience a clinical-complications profile that is different from that in patients with β-thalassemia major. In this article, a variety of clinical morbidities are explored, and their associations with the underlying disease pathophysiology and risk factors are examined. These involve several organs and organ systems including the vasculature, heart, liver, endocrine glands, bone, and the extramedullary hematopoietic system. The effects of some therapeutic interventions on the development of clinical complications are also discussed.
Topics: Anticoagulants; Blood Transfusion; Endocrine System Diseases; Hematopoiesis, Extramedullary; Humans; Hypertension, Pulmonary; Iron; Iron Chelating Agents; Iron Overload; Leg Ulcer; Risk Factors; Splenectomy; Thromboembolism; Thrombophilia; beta-Thalassemia
PubMed: 22762026
DOI: 10.1101/cshperspect.a013482 -
The Indian Journal of Medical Research Oct 2011In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to... (Review)
Review
In Southeast Asia α-thalassaemia, β-thalassaemia, haemoglobin (Hb) E and Hb Constant Spring (CS) are prevalent. The abnormal genes in different combinations lead to over 60 different thalassaemia syndromes, making Southeast Asia the locality with the most complex thalassaemia genotypes. The four major thalassaemic diseases are Hb Bart's hydrops fetalis (homozygous α-thalassaemia 1), homozygous β-thalassaemia, β-thalassaemia/Hb E and Hb H diseases. α-Thalassaemia, most often, occurs from gene deletions whereas point mutations and small deletions or insertions in the β-globin gene sequence are the major molecular defects responsible for most β-thalassaemias. Clinical manifestations of α-thalassaemia range from asymptomatic cases with normal findings to the totally lethal Hb Bart's hydrops fetalis syndrome. Homozygosity of β-thalassaemia results in a severe thalassaemic disease while the patients with compound heterozygosity, β-thalassaemia/Hb E, present variable severity of anaemia, and some can be as severe as homozygous β-thalassaemia. Concomitant inheritance of α-thalassaemia and increased production of Hb F are responsible for mild clinical phenotypes in some patients. However, there are still some unknown factors that can modulate disease severity in both α- and β-thalassaemias. Therefore, it is possible to set a strategy for prevention and control of thalassaemia, which includes population screening for heterozygotes, genetic counselling and foetal diagnosis with selective abortion of affected pregnancies.
Topics: Asia, Southeastern; Gene Deletion; Hemoglobin E; Hemoglobins, Abnormal; Humans; Point Mutation; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 22089614
DOI: No ID Found -
American Journal of Hematology Nov 2009
Topics: Blood Cells; Crystallization; Diagnostic Imaging; Female; Hemoglobin C; Heterozygote; Humans; Middle Aged; beta-Thalassemia
PubMed: 19790254
DOI: 10.1002/ajh.21534 -
TheScientificWorldJournal 2013In humans, β -thalassemia dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis.... (Review)
Review
In humans, β -thalassemia dyserythropoiesis is characterized by expansion of early erythroid precursors and erythroid progenitors and then ineffective erythropoiesis. This ineffective erythropoiesis is defined as a suboptimal production of mature erythrocytes originating from a proliferating pool of immature erythroblasts. It is characterized by (1) accelerated erythroid differentiation, (2) maturation blockade at the polychromatophilic stage, and (3) death of erythroid precursors. Despite extensive knowledge of molecular defects causing β -thalassemia, less is known about the mechanisms responsible for ineffective erythropoiesis. In this paper, we will focus on the underlying mechanisms leading to premature death of thalassemic erythroid precursors in the bone marrow.
Topics: Bone Marrow Cells; Cell Differentiation; Erythrocytes; Erythropoiesis; Humans; Models, Biological; Stem Cells; beta-Thalassemia
PubMed: 23606813
DOI: 10.1155/2013/394295 -
Annals of Global Health Jun 2021Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Blood transfusion is a traditional treatment for β-thalassemia (β-thal) that improves the patients' anemia and lifespan, but it may lead to iron overload in parenchymal tissue organs and endocrine glands that cause their dysfunctions as the iron regulatory system can't excrete excess iron from the bloodstream.
OBJECTIVE
To evaluate the prevalence of iron-related complications (short stature, growth retardation, and growth hormone deficiency) in β-thalassemia major (TM) patients.
METHODS
We performed an electronic search in PubMed, Scopus, and Web of Sciences to evaluate the prevalence of growth hormone impairment in β-thalassemia major (TM) patients worldwide. Qualities of eligible studies were assessed by the Joanna Briggs Institute checklist for the prevalence study. We used Comprehensive Meta-Analysis (Version 2) to calculate the event rate with 95% CIs, using a random-effects model for all analyses.
FINDINGS
Seventy-four studies were included from five continents between 1978 and 2019; 70.27% (Asia), 16.21% (Europe), 6.75% (Africa), 2.70% (America), 1.35% (Oceania), and 2.70% (Multicenter). The overall mean age of the participants was about 14 years. The pooled prevalence of short stature (ST) was 48.9% (95% CI 35.3-62.6) and in male was higher than female (61.9%, 95% CI 53.4-69.7 vs. 50.9%, CI 41.8-59.9). The pooled prevalence of growth retardation (GR) was 41.1% and in male was higher than in female (51.6%, 95% CI 17.8-84 vs. 33.1%, CI 9.4-70.2). The pooled prevalence of growth hormone deficiency (GHD) was 26.6% (95% CI 16-40.8).
CONCLUSION
Our study revealed that near half of thalassemia patients suffer from growth impairments. However, regular evaluation of serum ferritin levels, close monitoring in a proper institute, suitable and acceptable treatment methods besides regular chelation therapy could significantly reduce the patients' complications.
Topics: Adolescent; Blood Transfusion; Body Height; Dwarfism; Endocrine System Diseases; Female; Humans; Iron Overload; Male; beta-Thalassemia
PubMed: 34164261
DOI: 10.5334/aogh.3184 -
Blood Oct 2011β-thalassemia is a disease characterized by anemia and is associated with ineffective erythropoiesis and iron dysregulation resulting in iron overload. The peptide... (Review)
Review
β-thalassemia is a disease characterized by anemia and is associated with ineffective erythropoiesis and iron dysregulation resulting in iron overload. The peptide hormone hepcidin regulates iron metabolism, and insufficient hepcidin synthesis is responsible for iron overload in minimally transfused patients with this disease. Understanding the crosstalk between erythropoiesis and iron metabolism is an area of active investigation in which patients with and models of β-thalassemia have provided significant insight. The dependence of erythropoiesis on iron presupposes that iron demand for hemoglobin synthesis is involved in the regulation of iron metabolism. Major advances have been made in understanding iron availability for erythropoiesis and its dysregulation in β-thalassemia. In this review, we describe the clinical characteristics and current therapeutic standard in β-thalassemia, explore the definition of ineffective erythropoiesis, and discuss its role in hepcidin regulation. In preclinical experiments using interventions such as transferrin, hepcidin agonists, and JAK2 inhibitors, we provide evidence of potential new treatment alternatives that elucidate mechanisms by which expanded or ineffective erythropoiesis may regulate iron supply, distribution, and utilization in diseases such as β-thalassemia.
Topics: Animals; Antimicrobial Cationic Peptides; Disease Models, Animal; Erythrocytes; Erythropoiesis; Hepcidins; Humans; Iron; beta-Thalassemia
PubMed: 21768301
DOI: 10.1182/blood-2011-03-283614 -
British Journal of Haematology Apr 2015Genetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The... (Review)
Review
Genetic disorders of haemoglobin, particularly the sickle cell diseases and the alpha and beta thalassaemias, are the commonest inherited disorders worldwide. The majority of affected births occur in low-income and lower-middle income countries. Screening programmes are a vital tool to counter these haemoglobinopathies by: (i) identifying individual carriers and allowing them to make informed reproductive choices, and (ii) generating population level gene-frequency estimates, to help ensure the optimal allocation of public health resources. For both of these functions it is vital that the screen performed is suitably sensitive. One popular first-stage screening option to detect carriers of beta thalassaemia in low-income countries is the One Tube Osmotic Fragility Test (OTOFT). Here we introduce a population genetic framework within which to quantify the likely sensitivity and specificity of the OTOFT in different epidemiological contexts. We demonstrate that interactions between the carrier states for beta thalassaemia and alpha thalassaemia, glucose-6-phosphate dehydrogenase deficiency and Southeast Asian Ovalocytosis have the potential to reduce the sensitivity of OTOFTs for beta thalassaemia heterozygosity to below 70%. Our results therefore caution against the widespread application of OTOFTs in regions where these erythrocyte variants co-occur.
Topics: Elliptocytosis, Hereditary; Epistasis, Genetic; Female; Gene Frequency; Glucosephosphate Dehydrogenase Deficiency; Humans; Male; Mass Screening; Models, Biological; Osmotic Fragility; beta-Thalassemia
PubMed: 25521998
DOI: 10.1111/bjh.13241