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Zhonghua Yi Xue Yi Chuan Xue Za Zhi =... Mar 2020Alpha-thalassemia is an autosomal recessive genetic disease as well as a relatively common hemoglobinopathy. Severe alpha-thalassemia (also known as Hb Bart's Hydrops...
Alpha-thalassemia is an autosomal recessive genetic disease as well as a relatively common hemoglobinopathy. Severe alpha-thalassemia (also known as Hb Bart's Hydrops fetalis syndrome) and intermediate alpha-thalassemia (also known as Hb H disease) are among the most common birth defects in southern China. To implement carrier screening and large population prevention program in high incidence areas can significantly reduce the incidence of alpha-thalassemia. This guideline was established by combining the discoveries of basic research, clinical research and guidelines from other countries and the actual data of Chinese population. It has summarized the medical genetics knowledge and key points in the clinical treatment for alpha-thalassemia, and provided suggestions for the clinical diagnosis and standard management of patients.
Topics: China; Genetics, Medical; Hemoglobins, Abnormal; Humans; Hydrops Fetalis; Practice Guidelines as Topic; alpha-Thalassemia
PubMed: 32128738
DOI: 10.3760/cma.j.issn.1003-9406.2020.03.003 -
International Journal of Environmental... Oct 2020Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's... (Meta-Analysis)
Meta-Analysis
Alpha(α)-thalassemia is a blood disorder caused by many types of inheritable α-globin gene mutations which causes no-to-severe clinical symptoms, such as Hb Bart's hydrops fetalis that leads to early foetal death. Therefore, the aim of this meta-analysis was to provide an update from year 2010 to 2020 on the prevalence of α-thalassemia in Southeast Asia. A systematic literature search was performed using PubMed and SCOPUS databases for related studies published from 2010 to 2020, based on specified inclusion and exclusion criteria. Heterogeneity of included studies was examined with the I2 index and Q-test. Funnel plots and Egger's tests were performed in order to determine publication bias in this meta-analysis. Twenty-nine studies with 83,674 subjects were included and pooled prevalence rates in this meta-analysis were calculated using random effect models based on high observed heterogeneity (I2 > 99.5, -value < 0.1). Overall, the prevalence of α-thalassemia is 22.6%. The highest α-thalassemia prevalence was observed in Vietnam (51.5%) followed by Cambodia (39.5%), Laos (26.8%), Thailand (20.1%), and Malaysia (17.3%). No publication bias was detected. Conclusions: This meta-analysis suggested that a high prevalence of α-thalassemia occurred in selected Southeast Asia countries. This meta-analysis data are useful for designing thalassemia screening programs and improve the disease management.
Topics: Asia, Southeastern; Humans; Prevalence; alpha-Thalassemia
PubMed: 33050119
DOI: 10.3390/ijerph17207354 -
Hemoglobin Jul 2018Hemoglobinopathies are the most common monogenic diseases in the world, causing many health problems worldwide. In Egypt, thalassemia is the most common cause of chronic...
Hemoglobinopathies are the most common monogenic diseases in the world, causing many health problems worldwide. In Egypt, thalassemia is the most common cause of chronic hemolytic anemia and correlated with significant morbidity and mortality. One thousand Egyptian newborns were screened to detect α-thalassemia (α-thal) deletions using polymerase chain reaction (PCR)-based DNA analysis of cord blood samples. Ninety-one cases (9.1%) of the studied samples were proved to have at least one of the α genes deleted and 851 cases (85.1%) were normal by PCR analysis, while 58 samples (5.8%) failed to be amplified so further DNA analysis could not be done. In the studied group with α gene deletions, we found different types including silent carriers with only one α-globin gene deleted (3.1%), α-thal trait with two α-globin genes deleted (4.2%), Hb H disease with three α-globin genes deleted (1.8%) and no cases carrying Hb Bart's disease with loss of four α-globin genes. We determined the deletional spectrum of α-thal, which might be used in the future for molecular investigations of the disease in susceptible patients in our population.
Topics: Anemia, Hemolytic; Chronic Disease; Egypt; Female; Genotype; Humans; Infant, Newborn; Male; Mass Screening; Prevalence; Sequence Analysis, DNA; Sequence Deletion; alpha-Thalassemia
PubMed: 30422721
DOI: 10.1080/03630269.2018.1527231 -
Best Practice & Research. Clinical... Feb 2017Thalassemia is a significant health problem worldwide. Prenatal diagnosis is the only effective way to prevent the birth of a fetus with severe thalassemias, which... (Review)
Review
Thalassemia is a significant health problem worldwide. Prenatal diagnosis is the only effective way to prevent the birth of a fetus with severe thalassemias, which include hemoglobin Bart's hydrops fetalis and thalassemia major. However, accurate prenatal diagnosis depends on the comprehensive consideration of the molecular basis of thalassemias. To make a correct decision, the obstetrician should have a certain understanding of the genetics of thalassemias. Here we present a brief introduction of some fundamental genetic knowledge of thalassemias, including the production of hemoglobin, structure and location of globin genes, hemoglobin switch, epidemiology, clinical classification, molecular and cellular pathology, genotype-phenotype correlation, and genetic modifiers. Furthermore, some unusual clinical cases that cannot be explained by Mendel's laws are described. On the basis of a thorough understanding of the above information, clinicians should have the ability to precisely diagnose thalassemia patients and provide applicable genetic counselling to the affected families.
Topics: Female; Genetic Association Studies; Hemoglobins; Hemoglobins, Abnormal; Humans; Hydrops Fetalis; Pregnancy; Prenatal Diagnosis; alpha-Thalassemia; beta-Thalassemia
PubMed: 27876354
DOI: 10.1016/j.bpobgyn.2016.10.012 -
Scientific Reports Jun 2022Thalassemia is a group of common hereditary anemias that cause significant morbidity and mortality worldwide. However, precisely diagnosing thalassemia, especially rare...
Thalassemia is a group of common hereditary anemias that cause significant morbidity and mortality worldwide. However, precisely diagnosing thalassemia, especially rare thalassemia variants, is still challenging. Long-range PCR and long-molecule sequencing on the PacBio Sequel II platform utilized in this study could cover the entire HBA1, HBA2 and HBB genes, enabling the diagnosis of most of the common and rare types of thalassemia variants. In this study, 100 cases of suspected thalassemia were subjected to traditional thalassemia testing and third-generation sequencing for thalassemia genetic diagnosis. Compared with traditional diagnostic methods, an additional 10 cases of rare clinically significant variants, including 3 cases of structure variants and 7 cases of single nucleotide variations (SNVs) were identified, of which a case with - α subtype III (- α) was first identified and validated in the Chinese population. Other rare variants of 11.1 kb deletions (- 11.1/αα), triplicate α-globin genes (aaa/αα) and rare SNVs have also been thoroughly detected. The results showed that rare thalassemia variants are not rare but have been misdiagnosed by conventional methods. The results further validated third-generation sequencing as a promising method for rare thalassemia genetic testing.
Topics: Genotype; Humans; Mutation; Sequence Analysis, DNA; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 35701592
DOI: 10.1038/s41598-022-14038-8 -
Medicine Mar 2022There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α-... (Observational Study)
Observational Study
There is no information concerning the prevalence of thalassemia among pregnant women in Hubei Province currently. This study is aimed to explore the prevalence of α- and β-thalassemia genotypes among pregnant women in Hubei Province, and to explore the clinically applicable screening approach, as well as to investigate the pregnancy outcomes of α- and β-thalassemia carriers.Pregnant participants were recruited from 4 hospitals for the screening of α- and β-thalassemia mutations in Hubei Province. Polymerase Chain Reaction and flow cytometry methods were used to examine α- and β-thalassemia mutations. The hematological parameters and pregnancy outcomes of α- and β-thalassemia carriers were obtained from the hospital information system. The chi-square tests were used to evaluate the difference in hematological parameters between pregnant thalassemia carriers and the control group.Among 11,875 participants, 414 (3.49%) were confirmed with α-thalassemia carriers, 228 (1.92%) were confirmed with β-thalassemia carriers, and 3 (0.03%) were confirmed with both α- and β-thalassemia carriers. The frequency of -α3.7 accounted for 2.05% and it was the most frequent genotype of α-thalassemia; the proportion of IVS-II-654 was 0.85% and it was the most frequent genotype of β-thalassemia in Hubei Province. Furthermore, the proportion of patients with low mean corpuscular volume (MCV) or mean cell hemoglobin (MCH) values was accounted for 36.64% and 93.97% among α-thalassemia and β-thalassemia carriers, respectively. And participants with normal MCV and MCH values were accounted for 95.07% among non-thalassemia participants. High prevalence of pregnancy-induced diabetes (16.97%), preterm birth (9.96%), pregnancy-induced hypertension (8.12%), and low birth weight (5.90%) were observed among pregnant thalassemia carriers.MCV and MCH values were suggested to apply on the preliminary screening of pregnant β-thalassemia; however, it's unpractical on that of α-thalassemia. Furthermore, thalassemia carriers might have a high risk of negative pregnancy outcomes. These findings could be useful for the preliminary screening of thalassemia and perinatal care for the pregnant thalassemia carriers.
Topics: China; Diabetes, Gestational; Female; Genotype; Hemoglobins; Humans; Hypertension, Pregnancy-Induced; Infant, Low Birth Weight; Infant, Newborn; Male; Polymerase Chain Reaction; Pregnancy; Pregnancy Complications, Hematologic; Pregnant Women; Premature Birth; Prevalence; alpha-Thalassemia; beta-Thalassemia
PubMed: 35244037
DOI: 10.1097/MD.0000000000028790 -
Transfusion Dec 2018The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical... (Clinical Trial)
Clinical Trial
BACKGROUND
The severe forms of thalassemia are the most common inherited anemias managed with regular blood transfusion therapy. Transfusion policies and complications are critical to quality of life and survival, but there is a lack of standardized care.
STUDY DESIGN AND METHODS
A survey of 58 items was completed in 2016 by 11 centers in California, Washington, Oregon, Nevada, and Arizona providing long-term care for thalassemia. The questionnaire addressed demographic information, transfusion practices and complications, and educational needs.
RESULTS
The centers followed 717 patients with β-thalassemia (314, 43.8%) or α-thalassemia (394, 55%). One-third (34.7%) of patients were transfusion-dependent. Indications and goals of transfusion therapy differed between centers. Prestorage leukoreduction was universal, while routine irradiation of units was limited to one site. Red blood cell antigen phenotype was determined before the first transfusion and patients received Rh/Kell-matched units. However, more than half of the transfused patients had received blood at multiple hospitals within or outside the United States. Alloantibodies were seen in 16.9% of transfused group, but management of such patients was variable. Unusual or emerging transfusion-transmitted pathogens were not observed. Multiple educational needs were recognized, with iron overload as the biggest challenge; the approach to iron chelation varied within the group.
CONCLUSION
This study identified many patients not included in earlier surveys limited to major national centers, suggesting that the thalassemia population in the United States is vastly underestimated. Lack of evidence-based guidelines is a barrier to optimal care, which should be addressed through regional consortia of thalassemia centers.
Topics: Adult; Erythrocyte Transfusion; Female; Humans; Isoantibodies; Kell Blood-Group System; Male; Rh-Hr Blood-Group System; Surveys and Questionnaires; United States; alpha-Thalassemia; beta-Thalassemia
PubMed: 30260477
DOI: 10.1111/trf.14875 -
Blood Cells, Molecules & Diseases Dec 2015HbH disease had been introduced as a mild anemia disease. It recently has become the most challenging hemoglobinopathy due to the increasingly described genotype... (Review)
Review
HbH disease had been introduced as a mild anemia disease. It recently has become the most challenging hemoglobinopathy due to the increasingly described genotype patterns and very variable phenotypic presentations in different ethnics. Phenotypic severity of HbH syndrome is not simply related to the degree of α-globin deficiency and being influenced by several environmental and/or genetic factors. Hence, more investigation needs to identify factors like other genetic loci linked and/or unlinked to the α-globin genes affecting molecular mechanisms that influence clinical expression of HbH disease. Altogether, the complicated pathophysiology of HbH disease makes it to be known as a poorly understood syndrome. It may offer the hypothesis that it is a multifactorial disease, which needs to be investigated by more comprehensive genetic approach like genome wide association studies (GWAS) looking for genetic variants. Moreover, extended haplotype analysis to find out probable specific association between haplotypes of modifier genes and disease severity in patients with a specific HbH genotype may be a key point. In this review, we aim to provide important information regarding phenotypic presentation of different genotypes that have been described worldwide. It may help geneticists regarding challenging health care aspects of HbH disease in a specific ethnic.
Topics: Combined Modality Therapy; Disease Management; Genetic Association Studies; Genetic Counseling; Genetic Variation; Genotype; Hemoglobin H; Hemoglobins, Abnormal; Humans; Mutation; Phenotype; Prenatal Diagnosis; Syndrome; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 26460264
DOI: 10.1016/j.bcmd.2015.08.003 -
Scientific Reports Aug 2022α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening...
α-Thalassemia is a common inherited blood disorder manifested mainly by the deletions of α-globin genes. In geographical areas with high carrier frequencies, screening of α-thalassemia carrier state is therefore of vital importance. This study presents a novel method for identifying female carriers of common α-thalassemia deletions using samples routinely taken for non-invasive prenatal tests for screening of fetal chromosomal aneuploidies. A total of 68,885 Vietnamese pregnant women were recruited and α-thalassemia statuses were determined by gap-PCR, revealing 5344 women (7.76%) carried deletions including αα/-- (4.066%), αα/-α (2.934%), αα/-α (0.656%), and rare genotypes (0.102%). A two-stage model was built to predict these α-thalassemia deletions from targeted sequencing of the HBA gene cluster on maternal cfDNA. Our method achieved F1-scores of 97.14-99.55% for detecting the three common genotypes and 94.74% for detecting rare genotypes (-α/-α, αα/--, -α/--, -α/--). Additionally, the positive predictive values were 100.00% for αα/αα, 99.29% for αα/--, 94.87% for αα/-α, and 96.51% for αα/-α; and the negative predictive values were 97.63%, 99.99%, 99.99%, and 100.00%, respectively. As NIPT is increasingly adopted for pregnant women, utilizing cfDNA from NIPT to detect maternal carriers of common α-thalassemia deletions will be cost-effective and expand the benefits of NIPT.
Topics: Cell-Free Nucleic Acids; China; Female; Genotype; Humans; Mutation; Polymerase Chain Reaction; Pregnancy; alpha-Globins; alpha-Thalassemia; beta-Thalassemia
PubMed: 35945425
DOI: 10.1038/s41598-022-17718-7 -
Clinical Chemistry Mar 2023This is an editorial focusing on the clinical perspective of a long-read sequencing method in the prenatal diagnosis of alpha- and beta-thalassemia, including a...
This is an editorial focusing on the clinical perspective of a long-read sequencing method in the prenatal diagnosis of alpha- and beta-thalassemia, including a comparison between this method and standard PCR-based methods. Though incremental, the increased sensitivity and specificity using long-read sequencing is an important advantage of this methodology in the prenatal diagnostic arena due to false positive or false negative results having greater consequence when a family is making decisions about their pregnancy.
Topics: Pregnancy; Female; Humans; alpha-Thalassemia; Prenatal Diagnosis; beta-Thalassemia; Sequence Analysis, DNA; Sensitivity and Specificity
PubMed: 36648456
DOI: 10.1093/clinchem/hvac223