Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Advances in the management of α-thalassemia major: reasons to be optimistic.

ABSTRACT: α-Thalassemia major (ATM) is a severe disease resulting from deletions in all 4 copies of the α-globin gene. Although it is usually fatal before birth, the advent of in utero transfusions has enabled survival of a growing number of children. Postnatal therapy consists of chronic transfusions or stem cell transplantation, similar to patients with β-thalassemia major. In this review, we discuss the experience with postnatal stem cell transplantation in patients with ATM, as well as the ongoing phase 1 clinical trial of in utero stem cell transplantation for this condition.

SUBMITTER: Horvei P

PROVIDER: S-EPMC8791144 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Advances in the management of α-thalassemia major: reasons to be optimistic.

Horvei Paulina P MacKenzie Tippi T Kharbanda Sandhya S

Hematology. American Society of Hematology. Education Program 20211201 1

α-Thalassemia major (ATM) is a severe disease resulting from deletions in all 4 copies of the α-globin gene. Although it is usually fatal before birth, the advent of in utero transfusions has enabled survival of a growing number of children. Postnatal therapy consists of chronic transfusions or stem cell transplantation, similar to patients with β-thalassemia major. In this review, we discuss the experience with postnatal stem cell transplantation in patients with ATM, as well as the ongoing pha ...[more]

PMID: 34889445

Similar Datasets

Consensus statement for the perinatal management of patients with α thalassemia major.

Project description: Not available

| S-EPMC8714716 | biostudies-literature

Novel Therapeutic Advances in β-Thalassemia.

Project description:The main characteristic of the pathophysiology of β-thalassemia is reduced β-globin chain production. The inevitable imbalance in the α/β-globin ratio and α-globin accumulation lead to oxidative stress in the erythroid lineage, apoptosis, and ineffective erythropoiesis. The result is compensatory hematopoietic expansion and impaired hepcidin production that causes increased intestinal iron absorption and progressive iron overload. Chronic hemolysis and red blood cell transfusions also contribute to iron tissue deposition. A better understanding of the underlying mechanisms led to the detection of new curative or "disease-modifying" therapeutic options. Substantial evolvement has been made in allogeneic hematopoietic stem cell transplantation with current clinical trials investigating new condition regimens as well as different donors and stem cell source options. Gene therapy has also moved forward, and phase 2 clinical trials with the use of β-globin insertion techniques have recently been successfully completed leading to approval for use in transfusion-dependent patients. Genetic and epigenetic manipulation of the γ- or β-globin gene have entered the clinical trial setting. Agents such as TGF-β ligand traps and pyruvate kinase activators, which reduce the ineffective erythropoiesis, have been tested in clinical trials with favorable results. One TGF-β ligand trap, luspatercept, has been approved for use in adults with transfusion-dependent β-thalassemia. The induction of HbF with the phosphodiesterase 9 inhibitor IMR-687, which increase cyclic guanosine monophosphate, is currently being tested. Another therapeutic approach is to target the dysregulation of iron homeostasis, using, for example, hepcidin agonists (inhibitors of TMPRSS6 and minihepcidins) or ferroportin inhibitors (VIT-2763). This review provides an update on the novel therapeutic options that are presently in development at the clinical level in β-thalassemia.

| S-EPMC8235056 | biostudies-literature

Watershed Infarct in Beta-Thalassemia Major Patient.

Project description:Background. The mechanism of stroke in beta-thalassemia was reported previously as cardioembolic and hypercoagulable state. However, there is no report of watershed infarct in beta-thalassemia anemia. Method. We present an adult ?-thalassemia major patient with manifest asymptomatic chronic left carotid occlusion who suffered watershed infarct. Result. In the presence of asymptomatic chronic left internal carotid occlusion, we assumed that severe anemia (hemoglobin = 3) at admission leads to watershed infarct. Conclusion. Watershed infarct seems to be the cause of stroke in cases of ?-thalassemia major with severe anemia. Blood transfusion can be applied in the setting of acute brain ischemia in such high risk patients.

| S-EPMC5385913 | biostudies-other

Molecular Analysis of Non-Transfusion Dependent Thalassemia Associated with Hemoglobin E-β-Thalassemia Disease without α-Thalassemia.

Project description:BackgroundThe finding of many Thai Hb E-β0-thalassemia patients with non-transfusion dependent thalassemia (NTDT) phenotype without co-inheritance of α-thalassemia has prompted us to investigate the existence of other genetic modifying factors.MethodsStudy was done on 122 adult Thai patients with NTDT Hb E-β-thalassemia patients without co-inheritance of α-thalassemia. Multiple single-nucleotide polymorphisms (SNPs) associated with γ-globin gene expression including the Gγ-XmnI of HBG2 gene, rs2297339, rs4895441, and rs9399137 of the HBS1L-MYB gene, rs4671393 in the BCL11A gene, and G176AfsX179, T334R, R238H and -154 (C-T) in the KLF1 gene were investigated using PCR and related techniques.ResultsHeterozygous and homozygous for Gγ-XmnI of HBG2 gene were detected at 70.5% and 7.4%, respectively. Further DNA analysis identified the rs2297339 (C-T), rs4895441 (A-G), and rs9399137 (T-C) of HBS1L-MYB gene in 86.9%, 25.4%, and 23.0%, respectively. The rs4671393 (G-A) of the BCL11A gene was found at 31.2%. For the KLF1 gene, only T334R was detected at 9.0%.ConclusionsIt was found that these SNPs, when analyzed in combination, could explain the mild phenotypic expression of all cases. These results underline the importance of these informative SNPs on phenotypic expression of Hb E-β-thalassemia patients.

| S-EPMC6613625 | biostudies-literature

The impact of in utero transfusions on perinatal outcomes in patients with alpha thalassemia major: the UCSF registry.

Project description:Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.

| S-EPMC9860434 | biostudies-literature

Molecular Aspects of Bone Resorption in ?-Thalassemia Major.

Project description:?-thalassemia is the most common single gene disorder worldwide, in which hemoglobin ?-chain production is decreased. Today, the life expectancy of thalassemic patients is increased because of a variety of treatment methods; however treatment related complications have also increased. The most common side effect is osteoporosis, which usually occurs in early adulthood as a consequence of increased bone resorption. Increased bone resorption mainly results from factors such as delayed puberty, diabetes mellitus, hypothyroidism, ineffective hematopoiesis as well as hyperplasia of the bone marrow, parathyroid gland dysfunction, toxic effect of iron on osteoblasts, growth hormone (GH) and insulin-like growth factor-1 (IGF-1) deficiency. These factors disrupt the balance between osteoblasts and osteoclasts by interfering with various molecular mechanisms and result in decreased bone density. Given the high prevalence of osteopenia and osteoporosis in thalassemic patients and complexity of their development process, the goal of this review is to evaluate the molecular aspects involved in osteopenia and osteoporosis in thalassemic patients, which may be useful for therapeutic purposes.

| S-EPMC4503833 | biostudies-other

Economic burden of beta-thalassemia/Hb E and beta-thalassemia major in Thai children.

Project description:BackgroundHemoglobin E beta-thalassemia (beta-thalassemia/Hb E) has a variable severity, and the cost of treatment has not been well studied. The aim of this study was to analyze the societal cost of caring for children with beta-thalassemias in Thailand. The study was designed as a prevalence-based cost-of-illness analysis in a societal perspective. Medical records from three public hospitals of children aged 2-18 years with beta-thalassemia/Hb E and homozygous beta-thalassemia were reviewed for direct medical cost determination. For direct non-medical cost and indirect cost, a family member was interviewed.FindingsIt was found that 201 patients with beta-thalassemia/Hb E (91%) and homozygous beta-thalassemia (9%) were recruited for this study. Ninety-two (46%) were severe thalassemia and 109 (54%) were mild to moderate severity. The annual average cost of treatment was US$950; 59% was direct medical cost, 17% direct non-medical cost, and 24% indirect cost. The costs were differentiated by some potential predictors. Significant predictor variables were: hospital, health insurance scheme, blood transfusion pattern, and iron chelation drug use.ConclusionsThe average annual cost per patient was calculated, and the cost model was estimated. These would be applied for national planning, economic evaluation of treatment and prevention interventions, and budget impact analysis.

| S-EPMC2835719 | biostudies-literature

Management of insecticide resistance in the major Aedes vectors of arboviruses: Advances and challenges.

Project description:BackgroundThe landscape of mosquito-borne disease risk has changed dramatically in recent decades, due to the emergence and reemergence of urban transmission cycles driven by invasive Aedes aegypti and Ae. albopictus. Insecticide resistance is already widespread in the yellow fever mosquito, Ae. Aegypti; is emerging in the Asian tiger mosquito Ae. Albopictus; and is now threatening the global fight against human arboviral diseases such as dengue, yellow fever, chikungunya, and Zika. Because the panel of insecticides available for public health is limited, it is of primary importance to preserve the efficacy of existing and upcoming active ingredients. Timely implementation of insecticide resistance management (IRM) is crucial to maintain the arsenal of effective public health insecticides and sustain arbovirus vector control.Methodology and principal findingsThis Review is one of a series being generated by the Worldwide Insecticide resistance Network (WIN) and aims at defining the principles and concepts underlying IRM, identifying the main factors affecting the evolution of resistance, and evaluating the value of existing tools for resistance monitoring. Based on the lessons taken from resistance strategies used for other vector species and agricultural pests, we propose a framework for the implementation of IRM strategies for Aedes mosquito vectors.Conclusions and significanceAlthough IRM should be a fixture of all vector control programs, it is currently often absent from the strategic plans to control mosquito-borne diseases, especially arboviruses. Experiences from other public health disease vectors and agricultural pests underscore the need for urgent action in implementing IRM for invasive Aedes mosquitoes. Based on a plan developed for malaria vectors, here we propose some key activities to establish a global plan for IRM in Aedes spp.

| S-EPMC6786541 | biostudies-literature

α-Thalassemia, mental retardation, and myelodysplastic syndrome.

Project description:This article describes three rare syndromes in which the presence of α-thalassemia provided an important clue to the molecular basis of the underlying condition. It exemplifies how rare diseases allied with careful clinical observation can lead to important biological principles. Two of the syndromes, ATR-16 and ATR-X, are characterized by α-thalassemia in association with multiple developmental abnormalities including mental retardation. The third condition, ATMDS, is an acquired disorder in which α-thalassemia arises in the context of myelodysplasia. Intriguingly, mutations in the chromatin remodeling factor, ATRX, are common to both ATR-X syndrome and ATMDS.

| S-EPMC3475406 | biostudies-literature

Molecular Basis of α-Thalassemia in Iran

Project description:Alpha-thalassemia (α-thal) is probably the most prevalent monogenic condition in the world. Deletions are the most common types of mutations in α-thal, followed by point mutations and small insertion/deletion. In the context of national screening program for prevention of thalassemia and hemoglobinopathies in Iran, α-thal carriers have come to more attention. Therefore, the frequency and distribution of α-globin mutations in various regions of the country have been studied in recent years. A comprehensive search was performed in PubMed, Scopus, and national databases for finding reports on mutation detection in α-thal carriers and HbH disease with Iranian origin. The mutation data of 10849 α-thal carriers showed that -α3.7 and α-5NT were the most common deletional and nondeletional mutations, respectively. In HbH disease cases, the -α3.7/--MED was the most prevalent genotype. Overall, 42 different mutations have been identified in α-globin cluster reflecting the high heterogeneity of the mutations in Iranian populations.

| S-EPMC5712386 | biostudies-literature

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data