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Hematology/oncology Clinics of North... Apr 2018At present, thalassemia diseases are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia. This classification is based on the... (Review)
Review
At present, thalassemia diseases are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia. This classification is based on the clinical severity of patients determining whether they do require regular blood transfusions to survive (transfusion-dependent thalassemia) or not (non-transfusion-dependent thalassemia). In addition to the previous terminology of "thalassemia major" or "thalassemia intermedia," this classification has embraced all other forms of thalassemia syndromes such as α-thalassemia, hemoglobin E/β-thalassemia and combined α- and β-thalassemias. Definitive diagnosis of thalassemia and hemoglobinopathies requires a comprehensive workup from complete blood count, hemoglobin analysis, and molecular studies to identify mutations of globin genes.
Topics: Blood Transfusion; Genetic Association Studies; Genetic Testing; Hemoglobins; Humans; Mass Screening; Mutation; Phenotype; Thalassemia; alpha-Thalassemia; beta-Thalassemia
PubMed: 29458726
DOI: 10.1016/j.hoc.2017.11.006 -
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 -
The New England Journal of Medicine Nov 2014More than 100 varieties of α-thalassemia have been identified. Their geographic distribution and the challenges associated with screening, diagnosis, and management... (Review)
Review
More than 100 varieties of α-thalassemia have been identified. Their geographic distribution and the challenges associated with screening, diagnosis, and management suggest that α-thalassemias should have a higher priority on global public health agendas.
Topics: Child; Geography, Medical; Humans; Prenatal Diagnosis; Quality-Adjusted Life Years; alpha-Thalassemia
PubMed: 25390741
DOI: 10.1056/NEJMra1404415 -
Hematology/oncology Clinics of North... Apr 2023Clinical manifestations of α-thalassemia range from no symptoms to severe transfusion-dependent anemia. Alpha thalassemia trait is deletion of 1 to 2 α-globin genes,... (Review)
Review
Clinical manifestations of α-thalassemia range from no symptoms to severe transfusion-dependent anemia. Alpha thalassemia trait is deletion of 1 to 2 α-globin genes, whereas α-thalassemia major (ATM; Barts hydrops fetalis) is the deletion all 4 α genes. All other genotypes of intermediate severity are categorized as HbH disease, a vastly heterogenous group. Clinical spectrum is classified as mild, moderate, and severe by symptoms and need for intervention. Anemia in prenatal period may be fatal without intrauterine transfusions. New therapies to modify HbH disease or provide cure for ATM are under development.
Topics: Pregnancy; Female; Humans; alpha-Thalassemia; Hydrops Fetalis; Phenotype; Genotype; Anemia
PubMed: 36907606
DOI: 10.1016/j.hoc.2022.12.004 -
Hematology. American Society of... Dec 2021The thalassemias are inherited quantitative disorders of hemoglobin synthesis with a significant worldwide burden, which result in a wide spectrum of disease from the... (Review)
Review
The thalassemias are inherited quantitative disorders of hemoglobin synthesis with a significant worldwide burden, which result in a wide spectrum of disease from the most severe transfusion-dependent form to the mildest asymptomatic carrier state. In this article, we discuss the importance of carrier, prenatal, and newborn screening for thalassemia. We examine the rationale for who should be screened and when, as well as the current methodology for screening. Deficiencies in the newborn screening program are highlighted as well. With the advent of inexpensive and rapid genetic testing, this may be the most practical method of screening in the future, and we review the implications of population-based implementation of this strategy. Finally, a case-based overview of the approach for individuals with the trait as well as prospective parents who have a potential fetal risk of the disease is outlined.
Topics: Adult; Female; Genetic Testing; Humans; Infant; Infant, Newborn; Male; Prenatal Diagnosis; Young Adult; alpha-Thalassemia; beta-Thalassemia
PubMed: 34889395
DOI: 10.1182/hematology.2021000296 -
Hemoglobin Jan 2022The population of Viet Nam, is 96.2 million, of which 13.8% are carriers of thalassemia genes. Thalassemia/hemoglobinopathies carriers exist at different frequencies in... (Review)
Review
The population of Viet Nam, is 96.2 million, of which 13.8% are carriers of thalassemia genes. Thalassemia/hemoglobinopathies carriers exist at different frequencies in all 54 ethnic groups of the country. Gene carrier rate and globin gene mutation rate varies ethnically and topographically. The ethnic groups in the Northern Highland region have high rates of α- and β-thalassemia (α- and β-thal), while those in the Southern Middle region have high rates of α-thalassemia (α-thal) and Hb E (or codon 26) (: c.79G>A). The lowest is found in La Hu (0.23%), while the highest is found in Raglai (88.6%). Thalassemia prevention and control programs were introduced using prenatal and neonatal diagnosis for the prevention of new thalassemic births. Most existing thalassemia patients are undergoing supportive treatment with regular blood transfusions and iron chelation. Curative treatment by hematopoietic stem cell transplantation is available but is limited to a minority of the patients.
Topics: Female; Genotype; Hemoglobinopathies; Heterozygote; Humans; Infant, Newborn; Mutation; Pregnancy; Vietnam; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950578
DOI: 10.1080/03630269.2022.2069032 -
Blood Reviews Mar 2024α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin and thus varying... (Review)
Review
α-Thalassemia is an inherited blood disorder characterized by decreased synthesis of α-globin chains that results in an imbalance of α and β globin and thus varying degrees of ineffective erythropoiesis, decreased red blood cell (RBC) survival, chronic hemolytic anemia, and subsequent comorbidities. Clinical presentation varies depending on the genotype, ranging from a silent or mild carrier state to severe, transfusion-dependent or lethal disease. Management of patients with α-thalassemia is primarily supportive, addressing either symptoms (eg, RBC transfusions for anemia), complications of the disease, or its transfusion-dependence (eg, chelation therapy for iron overload). Several novel therapies are also in development, including curative gene manipulation techniques and disease modifying agents that target ineffective erythropoiesis and chronic hemolytic anemia. This review of α-thalassemia and its various manifestations provides practical information for clinicians who practice beyond those regions where it is found with high frequency.
Topics: Humans; beta-Thalassemia; alpha-Thalassemia; Erythropoiesis; Hematologic Diseases; Erythrocyte Transfusion; Iron Overload
PubMed: 38182489
DOI: 10.1016/j.blre.2023.101165 -
Hemoglobin Jan 2022The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about... (Review)
Review
The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about 40.0% (range 30.0-50.0%) to be carriers, and 2240 annual births for β-thalassemia major (β-TM). The overall prevalence of β-thalassemia (β-thal) and α-thalassemia (α-thal) were 40.9 and 39.6%, respectively. Currently, the specific epidemiological data regarding the abnormal gene frequency/mutations among different ethnic groups is unknown. In 2011, national guidelines for the Clinical Management of Patients with Thalassemia in Cambodia were developed and published by the Ministry of Health (MoH). Packed red cells (PRCs) are available at most referral hospitals (provincial hospitals). Oral iron chelators [deferiprone (DFP) and deferasirox (DFX)] are only available from a private pharmaceutical company. The future needs for Cambodia are to develop a national policy on the prevention or control of β-thal and α-thal, and a national registry of patients with thalassemia, to determine the gene frequency of α- and β-thal in different regions of the country, and to place the iron chelators on the list of essential medicines.
Topics: Cambodia; Hemoglobinopathies; Humans; Iron Chelating Agents; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950584
DOI: 10.1080/03630269.2021.2008956 -
[Rinsho Ketsueki] the Japanese Journal... 2021Thalassemia is caused by a reduced production of one globin chain due to a quantitative imbalance between the α-globin and non-α-globin chains that make up the...
Thalassemia is caused by a reduced production of one globin chain due to a quantitative imbalance between the α-globin and non-α-globin chains that make up the hemoglobin. It is classified into α- and β-thalassemia and characterized by microcytosis with polycythemia, and a Mentzer index of ≤13 aids in the diagnosis. In the genetic analysis of α-thalassemia, the Southeast Asian type was found to be the most common genetic subtype among Japanese and non-Japanese without a substantial difference. Conversely, the genetic analysis of β-thalassemia revealed differences in the types and frequencies of mutations between Japanese individuals and foreigners living in Japan, with Japanese-specific mutations such as -31 A→G (TATA box). Acquired α-thalassemia exists in exceptional cases, and cases of myelodysplastic syndrome with acquired Hemoglobin H disease have been reported as α-thalassemia myelodysplastic syndrome. Recent trials using a novel therapeutic agent, luspatercept, for transfusion-dependent β-thalassemia revealed that luspatercept safely and significantly reduces the transfusion volume.
Topics: Blood Transfusion; Humans; Japan; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 34497231
DOI: 10.11406/rinketsu.62.914 -
Hemoglobin Jan 2022The island nation of Sri Lanka with 22 million people (in 2020) has an estimated 2000 patients with severe thalassemia. The majority have β-thalassemia (β-thal) major... (Review)
Review
The island nation of Sri Lanka with 22 million people (in 2020) has an estimated 2000 patients with severe thalassemia. The majority have β-thalassemia (β-thal) major (β-TM), and Hb E (: c.79G>A)/β-thal accounts for most of the remainder. Carrier rate for α-thalassemia (α-thal) trait is 9.9% and β-thal trait is 2.5%, with very similar rates in the three major ethnic groups (Sinhalese, Tamils and Moors). The distribution of thalassemia type reveals a remarkable variation, even in this small island, mirroring historical distribution of malaria. Even though healthcare is provided free by the state including blood transfusions and chelation, the overall survival of patients of β-TM is still not on a par with that of the Mediterranean countries. A national thalassemia prevention program was set up in 2007, but overall success of the exercise based essentially on dissuasion of marriages is not very promising.
Topics: Humans; Phenotype; Sri Lanka; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950586
DOI: 10.1080/03630269.2022.2025826