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Hemoglobin Jan 2022Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry β-thalassemia (β-thal) and 2.6-11.0%... (Review)
Review
Indonesia is located along the 'Thalassemia Belt' and a hotspot for hemoglobinopathies. Around 3.0-10.0% of the population carry β-thalassemia (β-thal) and 2.6-11.0% of the population carry α-thalassemia (α-thal). It is estimated that around 2500 babies are born with β-thal major (β-TM) each year. At present, the cornerstone of treatment for β-TM in Indonesia remains supportive, including blood transfusions and iron chelation therapy. Hemovigilance systems in some cities are poor and it increases the risk of transfusion-transmitted infections and transfusion reactions. The availability of iron chelators remains uncertain, even in some rural areas, iron chelators do not exist. The poor adherence to iron chelation therapy and maintaining pretransfusion hemoglobin (Hb) levels above 9.0 g/dL are still a major issue in Indonesia. The cost of blood transfusion and iron chelation are covered by national health insurance. In line with the rise of life expectancy, the financial burden of thalassemia in Indonesia is increasing sharply. Thus, optimizing preventive programs may be the most suitable option for the current thalassemia condition in Indonesia.
Topics: Humans; Indonesia; Iron; Iron Chelating Agents; Transfusion Reaction; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950580
DOI: 10.1080/03630269.2021.2023565 -
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 -
Hemoglobin Jan 2022India bears a huge burden of hemoglobinopathies, and the most prevalent is thalassemia. The different types of thalassemia include minor, major and intermedia, based on... (Review)
Review
India bears a huge burden of hemoglobinopathies, and the most prevalent is thalassemia. The different types of thalassemia include minor, major and intermedia, based on the α/β-globin chain inequality. This review aimed to understand the current prevalence of thalassemia in different regions of India and communities affected by it, along with the management of β-thalassemia major (β-TM) and β-thalassemia (β-thal) minor patients. A comprehensive electronic search for relevant articles was conducted using two databases, PubMed and Science Direct. Articles published in English from India between January 2009 and September 2021 were included. Studies from other countries, genetic and molecular characterization studies, and articles published in other languages were excluded. The prevalence of β-thal trait in Central India ranged between 1.4 and 3.4%, while 0.94% β-TM was reported among the patients with anemia. In South India, the prevalence of β-thal trait was between 8.50 and 37.90% and β-TM was reported to be between 2.30 and 7.47%. Northern and Western Indian states had a higher thalassemic burden. In Eastern India, tribal populations had a higher prevalence of β-thal trait (0.00-30.50%), β-TM (0.36-13.20%) and other hemoglobinopathies [Hb E (: c.79G>A)/β-thal] (0.04-15.45%) than nontribal populations. Additionally, scheduled castes, scheduled tribes and other backward classes of low socioeconomic status and low literacy rates were affected by β-thal. Almost all Indian states reported β-thal; however, it is mostly concentrated in eastern and western parts of the country. Well-integrated strategies and effective implementation are needed at State and National levels to minimize the burden of β-thal.
Topics: Hemoglobinopathies; Humans; India; Mutation; Prevalence; alpha-Thalassemia; beta-Globins; beta-Thalassemia
PubMed: 35129043
DOI: 10.1080/03630269.2021.2001346 -
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 -
JAMA Network Open Oct 2023Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD... (Meta-Analysis)
Meta-Analysis
IMPORTANCE
Sickle cell disease (SCD) is a monogenic disorder, yet clinical outcomes are influenced by additional genetic factors. Despite decades of research, the genetics of SCD remain poorly understood.
OBJECTIVE
To assess all reported genetic modifiers of SCD, evaluate the design of associated studies, and provide guidelines for future analyses according to modern genetic study recommendations.
DATA SOURCES
PubMed, Web of Science, and Scopus were searched through May 16, 2023, identifying 5290 publications.
STUDY SELECTION
At least 2 reviewers identified 571 original, peer-reviewed English-language publications reporting genetic modifiers of human SCD phenotypes, wherein the outcome was not treatment response, and the comparison was not between SCD subtypes or including healthy controls.
DATA EXTRACTION AND SYNTHESIS
Data relevant to all genetic modifiers of SCD were extracted, evaluated, and presented following STREGA and PRISMA guidelines. Weighted z score meta-analyses and pathway analyses were conducted.
MAIN OUTCOMES AND MEASURES
Outcomes were aggregated into 25 categories, grouped as acute complications, chronic conditions, hematologic parameters or biomarkers, and general or mixed measures of SCD severity.
RESULTS
The 571 included studies reported on 29 670 unique individuals (50% ≤ 18 years of age) from 43 countries. Of the 17 757 extracted results (4890 significant) in 1552 genes, 3675 results met the study criteria for meta-analysis: reported phenotype and genotype, association size and direction, variability measure, sample size, and statistical test. Only 173 results for 62 associations could be cross-study combined. The remaining associations could not be aggregated because they were only reported once or methods (eg, study design, reporting practice) and genotype or phenotype definitions were insufficiently harmonized. Gene variants regulating fetal hemoglobin and α-thalassemia (important markers for SCD severity) were frequently identified: 19 single-nucleotide variants in BCL11A, HBS1L-MYB, and HBG2 were significantly associated with fetal hemoglobin (absolute value of Z = 4.00 to 20.66; P = 8.63 × 10-95 to 6.19 × 10-5), and α-thalassemia deletions were significantly associated with increased hemoglobin level and reduced risk of albuminuria, abnormal transcranial Doppler velocity, and stroke (absolute value of Z = 3.43 to 5.16; P = 2.42 × 10-7 to 6.00 × 10-4). However, other associations remain unconfirmed. Pathway analyses of significant genes highlighted the importance of cellular adhesion, inflammation, oxidative and toxic stress, and blood vessel regulation in SCD (23 of the top 25 Gene Ontology pathways involve these processes) and suggested future research areas.
CONCLUSIONS AND RELEVANCE
The findings of this comprehensive systematic review and meta-analysis of all published genetic modifiers of SCD indicated that implementation of standardized phenotypes, statistical methods, and reporting practices should accelerate discovery and validation of genetic modifiers and development of clinically actionable genetic profiles.
Topics: Humans; Fetal Hemoglobin; alpha-Thalassemia; Anemia, Sickle Cell; Genotype; Genetic Variation
PubMed: 37851445
DOI: 10.1001/jamanetworkopen.2023.37484 -
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 -
Life Science Alliance Dec 2023Our study aimed to investigate if genetic variants around 16p13.3's locus, associated with erythrocyte indices and HbA1c levels, predict α-thalassemia-related...
Our study aimed to investigate if genetic variants around 16p13.3's locus, associated with erythrocyte indices and HbA1c levels, predict α-thalassemia-related erythrocyte indices, cardiometabolic traits, and diabetes risk in Taiwanese individuals. We analyzed Taiwan Biobank data, including whole-genome sequencing from 1,493 participants and genotyping arrays from 129,542 individuals. First, we performed regional association analysis using whole-genome sequencing data to identify genetic variants significantly associated with erythrocyte indices, confirming their linkage disequilibrium with the α thalassemia -- deletion mutation, a common cause of α-thalassemia in Southeast Asian populations. Deletion mutation sequencing further validated these variants' association with α-thalassemia. Subsequently, we analyzed genotyping array data, revealing associations between specific genetic variants and cardiometabolic traits, including lipid profiles, HbA1c levels, bilirubin levels, and diabetes risk. Using Mendelian randomization, we established causal relationships between α-thalassemia-related erythrocyte indices and cardiometabolic traits, elucidating their role in diabetes susceptibility. Our findings highlight genetic variants around the α-globin genes as surrogate markers for common α-thalassemia mutations in Taiwan, emphasizing the causal links between α-thalassemia-related erythrocyte indices, cardiometabolic traits, and heightened diabetes risk.
Topics: Humans; alpha-Thalassemia; Glycated Hemoglobin; Phenotype; Diabetes Mellitus, Type 2; Cardiovascular Diseases
PubMed: 37788909
DOI: 10.26508/lsa.202302204 -
[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