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Blood Cells, Molecules & Diseases May 2018α-Thalassemia is an inherited, autosomal recessive, disorder characterized by a microcytic hypochromic anemia. It is one of the most common monogenic gene disorders in... (Review)
Review
α-Thalassemia is an inherited, autosomal recessive, disorder characterized by a microcytic hypochromic anemia. It is one of the most common monogenic gene disorders in the world population. The clinical severity varies from almost asymptomatic, to mild microcytic hypochromic, and to a lethal hemolytic condition, called Hb Bart's Hydrops Foetalis Syndrome. The molecular basis are usually deletions and less frequently, point mutations affecting the expression of one or more of the duplicated α-genes. The clinical variation and increase in disease severity is directly related to the decreased expression of one, two, three or four copies of the α-globin genes. Deletions and point mutations in the α-globin genes and their regulatory elements have been studied extensively in carriers and patients and these studies have given insight into the α-globin genes are regulated. By looking at naturally occurring deletions and point mutations, our knowledge of globin-gene regulation and expression will continue to increase and will lead to new targets of therapy.
Topics: Animals; Diagnosis, Differential; Disease Management; Genetic Association Studies; Genetic Counseling; Genetic Loci; Genotype; Humans; Mutation; Phenotype; alpha-Globins; alpha-Thalassemia
PubMed: 29032940
DOI: 10.1016/j.bcmd.2017.09.004 -
European Journal of Haematology Dec 2020β-thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron... (Review)
Review
β-thalassemia major is an inherited hemoglobinopathy that requires lifelong red blood cell transfusions and iron chelation therapy to prevent complications due to iron overload. Traditionally, β-thalassemia has been more common in certain regions of the world such as the Mediterranean, Middle East, and Southeast Asia. However, the prevalence of β-thalassemia is increasing in other regions, including Northern Europe and North America, primarily due to migration. This review summarizes the available data on the changing incidence and prevalence of β-thalassemia as well as factors influencing disease frequency. The data suggest that the epidemiology of β-thalassemia is changing: Migration has increased the prevalence of the disease in regions traditionally believed to have a low prevalence, while, at the same time, prevention and screening programs in endemic regions have reduced the number of affected individuals. Various approaches to prevention and screening have been used. Region-specific prevention and treatment programs, customized to align with local healthcare resources and cultural values, have been effective in identifying patients and carriers and providing information and care. Significant challenges remain in universally implementing these programs.
Topics: Disease Management; Disease Susceptibility; Emigration and Immigration; Geography, Medical; Global Health; Humans; Incidence; Population Surveillance; Prevalence; Public Health Surveillance; Risk Factors; beta-Thalassemia
PubMed: 32886826
DOI: 10.1111/ejh.13512 -
Cleveland Clinic Journal of Medicine Jan 2020Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States and causes significant disease-related morbidity including multiorgan damage, chronic... (Review)
Review
Sickle cell disease (SCD) is the most common hemoglobinopathy in the United States and causes significant disease-related morbidity including multiorgan damage, chronic anemia, and debilitating pain crises. Primary care physicians play a key role in the medical home model of care for adults with SCD. This review focuses on current recommendations for health maintenance and provides a brief summary of disease complications and current updates.
Topics: Adolescent; Adult; Anemia, Sickle Cell; Female; Humans; Male; Patient-Centered Care; Primary Health Care; United States; Young Adult
PubMed: 31990651
DOI: 10.3949/ccjm.87a.18051 -
CMAJ : Canadian Medical Association... Oct 2020
Topics: Diabetes Mellitus; Erythrocyte Indices; Humans; Iron Overload; Referral and Consultation; Thalassemia
PubMed: 33051316
DOI: 10.1503/cmaj.191613 -
Australian Journal of General Practice Mar 2019Anaemia in pregnancy is a common medical condition managed by general practitioners (GPs) in Australia.
BACKGROUND
Anaemia in pregnancy is a common medical condition managed by general practitioners (GPs) in Australia.
OBJECTIVE
The aim of this article is to raise awareness of anaemia that occurs in pregnancy, understand its increasing complexities with an expanding migrant population, identify at-risk groups and promote appropriate management.
DISCUSSION
With anaemia reportedly occurring in 25% of women in pregnancy and GPs managing the majority of preconception and early pregnancy care, it is important to have a sound understanding of the aetiology, risks and management options. While iron deficiency anaemia is most commonly seen, a more complex understanding in regard to other causes and haemoglobinopathy screening is required.
Topics: Adult; Anemia; Anemia, Iron-Deficiency; Australia; Avitaminosis; Female; Helminthiasis; Hemoglobinopathies; Humans; Iron; Iron Deficiencies; Mass Screening; Pregnancy; Pregnancy Complications; Prenatal Care
PubMed: 31256475
DOI: 10.31128/AJGP-08-18-4664 -
Brazilian Journal of Biology = Revista... 2021A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta...
A group of inherited blood defects is known as Thalassemia is among the world's most prevalent hemoglobinopathies. Thalassemias are of two types such as Alpha and Beta Thalassemia. The cause of these defects is gene mutations leading to low levels and/or malfunctioning α and β globin proteins, respectively. In some cases, one of these proteins may be completely absent. α and β globin chains form a globin fold or pocket for heme (Fe++) attachment to carry oxygen. Genes for alpha and beta-globin proteins are present in the form of a cluster on chromosome 16 and 11, respectively. Different globin genes are used at different stages in the life course. During embryonic and fetal developmental stages, γ globin proteins partner with α globin and are later replaced by β globin protein. Globin chain imbalances result in hemolysis and impede erythropoiesis. Individuals showing mild symptoms include carriers of alpha thalassemia or the people bearing alpha or beta-thalassemia trait. Alpha thalassemia causes conditions like hemolytic anemia or fatal hydrops fetalis depending upon the severity of the disease. Beta thalassemia major results in hemolytic anemia, growth retardation, and skeletal aberrations in early childhood. Children affected by this disorder need regular blood transfusions throughout their lives. Patients that depend on blood transfusion usually develop iron overload that causes other complications in the body systems like renal or hepatic impairment therefore, thalassemias are now categorized as a syndrome. The only cure for Thalassemias would be a bone marrow transplant, or gene therapy with currently no significant success rate. A thorough understanding of the molecular basis of this syndrome may provide novel insights and ideas for its treatment, as scientists have still been unable to find a permanent cure for this deadly disease after more than 87 years since it is first described in 1925.
Topics: Child, Preschool; Hemoglobins; Humans; Thalassemia; beta-Thalassemia
PubMed: 34495151
DOI: 10.1590/1519-6984.246062 -
International Journal of Laboratory... Sep 2022Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show... (Review)
Review
Hemoglobinopathies are the most common monogenic disorders in the world with an ever increasing global disease burden each year. As most hemoglobinopathies show recessive inheritance carriers are usually clinically silent. Programmes for preconception and antenatal carrier screening, with the option of prenatal diagnosis are considered beneficial in many endemic countries. With the development of genetic tools such as Array analysis and Next Generation Sequencing in addition to state of the art screening at the hematologic, biochemic and genetic level, have contributed to the discovery of an increasing number of rare rearrangements and novel factors influencing the disease severity over the recent years. This review summarizes the basic requirements for adequate carrier screening analysis, the importance of genotype-phenotype correlation and how this may lead to the unrevealing exceptional interactions causing a clinically more severe phenotype in otherwise asymptomatic carriers. A special group of patients are β-thalassemia carriers presenting with features of β-thalassemia intermedia of various clinical severity. The disease mechanisms may involve duplicated α-globin genes, mosaic partial Uniparental Isodisomy of chromosome 11p15.4 where the HBB gene is located or haplo-insufficiency of a non-linked gene SUPT5H on chromosome 19q, first described in two Dutch families with β-thalassemia trait without variants in the HBB gene.
Topics: Female; Genotype; Hemoglobinopathies; Humans; Nuclear Proteins; Phenotype; Pregnancy; Prenatal Diagnosis; Transcriptional Elongation Factors; alpha-Globins; beta-Thalassemia
PubMed: 36074711
DOI: 10.1111/ijlh.13885 -
Drugs Jul 2020Hemoglobinopathies are among the most common monogenic diseases worldwide. Approximately 1-5% of the global population are carriers for a genetic thalassemia mutation.... (Review)
Review
Hemoglobinopathies are among the most common monogenic diseases worldwide. Approximately 1-5% of the global population are carriers for a genetic thalassemia mutation. The thalassemias are characterized by autosomal recessive inherited defects in the production of hemoglobin. They are highly prevalent in the Mediterranean, Middle East, Indian subcontinent, and East and Southeast Asia. Due to recent migrations, however, the thalassemias are now becoming more common in Europe and North America, making this disease a global health concern. Currently available conventional therapies in thalassemia have many challenges and limitations. A better understanding of the pathophysiology of β-thalassemia in addition to key developments in optimizing transfusion programs and iron-chelation therapy has led to an increase in the life span of thalassemia patients and paved the way for new therapeutic strategies. These can be classified into three categories based on their efforts to address different features of the underlying pathophysiology of β-thalassemia: correction of the globin chain imbalance, addressing ineffective erythropoiesis, and improving iron overload. In this review, we provide an overview of the novel therapeutic approaches that are currently in development for β-thalassemia.
Topics: Blood Transfusion; Genetic Therapy; Humans; Iron Chelating Agents; Iron Overload; Molecular Targeted Therapy; beta-Thalassemia
PubMed: 32557398
DOI: 10.1007/s40265-020-01341-9 -
Viruses Mar 2023Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the... (Review)
Review
Investigations to understand the function and control of the globin genes have led to some of the most exciting molecular discoveries and biomedical breakthroughs of the 20th and 21st centuries. Extensive characterization of the globin gene locus, accompanied by pioneering work on the utilization of viruses as human gene delivery tools in human hematopoietic stem and progenitor cells (HPSCs), has led to transformative and successful therapies via autologous hematopoietic stem-cell transplant with gene therapy (HSCT-GT). Due to the advanced understanding of the β-globin gene cluster, the first diseases considered for autologous HSCT-GT were two prevalent β-hemoglobinopathies: sickle cell disease and β-thalassemia, both affecting functional β-globin chains and leading to substantial morbidity. Both conditions are suitable for allogeneic HSCT; however, this therapy comes with serious risks and is most effective using an HLA-matched family donor (which is not available for most patients) to obtain optimal therapeutic and safe benefits. Transplants from unrelated or haplo-identical donors carry higher risks, although they are progressively improving. Conversely, HSCT-GT utilizes the patient's own HSPCs, broadening access to more patients. Several gene therapy clinical trials have been reported to have achieved significant disease improvement, and more are underway. Based on the safety and the therapeutic success of autologous HSCT-GT, the U.S. Food and Drug Administration (FDA) in 2022 approved an HSCT-GT for β-thalassemia (Zynteglo™). This review illuminates the β-globin gene research journey, adversities faced, and achievements reached; it highlights important molecular and genetic findings of the β-globin locus, describes the predominant globin vectors, and concludes by describing promising results from clinical trials for both sickle cell disease and β-thalassemia.
Topics: Humans; beta-Thalassemia; Hematopoietic Stem Cell Transplantation; Genetic Vectors; Hemoglobinopathies; Anemia, Sickle Cell; Genetic Therapy; beta-Globins
PubMed: 36992422
DOI: 10.3390/v15030713 -
American Family Physician Mar 2022Thalassemia is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin. Ineffective...
Thalassemia is a group of autosomal recessive hemoglobinopathies affecting the production of normal alpha- or beta-globin chains that comprise hemoglobin. Ineffective production of alpha- or beta-globin chains may result in ineffective erythropoiesis, premature red blood cell destruction, and anemia. Chronic, severe anemia in patients with thalassemia may result in bone marrow expansion and extramedullary hematopoiesis. Thalassemia should be suspected in patients with microcytic anemia and normal or elevated ferritin levels. Hemoglobin electrophoresis may reveal common characteristics of different thalassemia subtypes, but genetic testing is required to confirm the diagnosis. Thalassemia is generally asymptomatic in trait and carrier states. Alpha-thalassemia major results in hydrops fetalis and is often fatal at birth. Beta-thalassemia major requires lifelong transfusions starting in early childhood (often before two years of age). Alpha- and beta-thalassemia intermedia have variable presentations based on gene mutation or deletion, with mild forms requiring only monitoring but more severe forms leading to symptomatic anemia and requiring transfusion. Treatment of thalassemia includes transfusions, iron chelation therapy to correct iron overload (from hemolytic anemia, intestinal iron absorption, and repeated transfusions), hydroxyurea, hematopoietic stem cell transplantation, and luspatercept. Thalassemia complications arise from bone marrow expansion, extramedullary hematopoiesis, and iron deposition in peripheral tissues. These complications include morbidities affecting the skeletal system, endocrine organs, heart, and liver. Life expectancy of those with thalassemia has improved dramatically over the past 50 years with increased availability of blood transfusions and iron chelation therapy, and improved iron overload monitoring. Genetic counseling and screening in high-risk populations can assist in reducing the prevalence of thalassemia.
Topics: Child, Preschool; Hematologic Diseases; Humans; Infant, Newborn; Iron; Iron Overload; Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 35289581
DOI: No ID Found