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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 -
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 -
International Journal of Laboratory... Sep 2022Hemoglobinopathies constitute some of the most common inherited disorders worldwide. Manifestations are very severe, patient management is difficult and treatment is not... (Review)
Review
Hemoglobinopathies constitute some of the most common inherited disorders worldwide. Manifestations are very severe, patient management is difficult and treatment is not easily accessible. Preimplantation genetic testing for monogenic disorders (PGT-M) is a valuable reproductive option for hemoglobinopathy carrier-couples as it precludes the initiation of an affected pregnancy. PGT-M is performed on embryos generated by assisted reproductive technologies and only those found to be free of the monogenic disorder are transferred to the uterus. PGT-M has been applied for 30 years now and β-thalassemia is one of the most common indications. PGT may also be applied for human leukocyte antigen typing to identify embryos that are unaffected and also compatible with an affected sibling in need of hemopoietic stem cell transplantation. PGT-M protocols have evolved from PCR amplification-based, where a small number of loci were analysed, to whole genome amplification-based, the latter increasing diagnostic accuracy, enabling the development of more generic strategies and facilitating multiple diagnoses in one embryo. Currently, numerous PGT-M cycles are performed for the simultaneous diagnosis of hemoglobinopathies and screening for chromosomal abnormalities in the embryo in an attempt to further improve success rates and increase deliveries of unaffected babies.
Topics: Embryo Transfer; Female; Genetic Testing; Hemoglobinopathies; Humans; Pregnancy; Preimplantation Diagnosis; beta-Thalassemia
PubMed: 35443077
DOI: 10.1111/ijlh.13851 -
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 -
Acta Clinica Croatica Dec 2020The world is struggling to deal with the corona pandemic. Effective therapies are still awaited due to the lack of understanding of the pathophysiological mechanism of... (Review)
Review
The world is struggling to deal with the corona pandemic. Effective therapies are still awaited due to the lack of understanding of the pathophysiological mechanism of the disease. Bearing recent research and clinical observations in mind, the authors propose a novel physiological mechanism of COVID-19 and explain development of COVID-19 related acute respiratory distress syndrome (ARDS) secondary to COVID-19 related hemoglobinopathy. It is a consistent observation that the radiological picture of COVID-19 related ARDS bears more resemblance to high altitude pulmonary edema (HAPE) than typical ARDS. There has been great controversy regarding this proposed similarity. The main argument from those objecting to this comparison is that the etiology is hypoxia in case of HAPE and inflammation in COVID-19 related ARDS. We propose that considering the recent bioinformatics prediction models, COVID-19 might first infect red blood cells CD147 and cause hemoglobin damage. The resulting hypoxemia may cause pulmonary hypoxic vasoconstriction leading to HAPE-like lung lesions. The now introduced alveolar hypoxia further exaggerates hemoglobinopathy hypoxemia leading to a vicious cycle. In this review, the authors recommend laboratory experiments to prove these hypotheses. The proposed physiological mechanism has significant therapeutic implications. If proven, the authors suggest the use of exchange transfusion as adjunct therapy and development of anti-CD147 drugs.
Topics: Altitude Sickness; COVID-19; Hemoglobinopathies; Humans; Pulmonary Edema; SARS-CoV-2
PubMed: 34285445
DOI: 10.20471/acc.2020.59.04.21 -
Ugeskrift For Laeger Oct 2021Hereditary anaemias are the most prevalent genetic disorders worldwide. Until recently, treatment options were mostly supportive or surgical, i.e. splenectomy. Recently,... (Review)
Review
Hereditary anaemias are the most prevalent genetic disorders worldwide. Until recently, treatment options were mostly supportive or surgical, i.e. splenectomy. Recently, several medical treatments designed for frequent haemoglobinopathies such as thalassaemia and sickle cell disease have become available, and numerous new clinical trials hold promise of many more to come. Even rare anaemias such as pyruvate kinase deficiency have promising clinical trials with targeted therapies. Together, these herald hope for future treatment options for patients living with hereditary anaemias, which is discussed in this review.
Topics: Anemia, Hemolytic, Congenital Nonspherocytic; Anemia, Sickle Cell; Hemoglobinopathies; Humans; Splenectomy; Thalassemia
PubMed: 34709160
DOI: No ID Found -
Cell Stem Cell Dec 2023Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating β-hemoglobinopathies....
Reactivating silenced γ-globin expression through the disruption of repressive regulatory domains offers a therapeutic strategy for treating β-hemoglobinopathies. Here, we used transformer base editor (tBE), a recently developed cytosine base editor with no detectable off-target mutations, to disrupt transcription-factor-binding motifs in hematopoietic stem cells. By performing functional screening of six motifs with tBE, we found that directly disrupting the BCL11A-binding motif in HBG1/2 promoters triggered the highest γ-globin expression. Via a side-by-side comparison with other clinical and preclinical strategies using Cas9 nuclease or conventional BEs (ABE8e and hA3A-BE3), we found that tBE-mediated disruption of the BCL11A-binding motif at the HBG1/2 promoters triggered the highest fetal hemoglobin in healthy and β-thalassemia patient hematopoietic stem/progenitor cells while exhibiting no detectable DNA or RNA off-target mutations. Durable therapeutic editing by tBE persisted in repopulating hematopoietic stem cells, demonstrating that tBE-mediated editing in HBG1/2 promoters is a safe and effective strategy for treating β-hemoglobinopathies.
Topics: Humans; Gene Editing; Fetal Hemoglobin; gamma-Globins; CRISPR-Cas Systems; Mutation; Hemoglobinopathies; Hematopoietic Stem Cells; Transcription Factors
PubMed: 37989316
DOI: 10.1016/j.stem.2023.10.007 -
International Journal of Molecular... Nov 2023Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ... (Review)
Review
Hemoglobinopathies, including β-thalassemia and sickle cell disease (SCD), are common genetic blood disorders. Endocrine disorders are frequent manifestations of organ damage observed mainly in patients with β-thalassemia and rarely in SCD. Iron overload, oxidative stress-induced cellular damage, chronic anemia, and HCV infection contribute to the development of endocrinopathies in β-thalassemia. The above factors, combined with vaso-occlusive events and microcirculation defects, are crucial for endocrine dysfunction in SCD patients. These endocrinopathies include diabetes mellitus, hypothyroidism, parathyroid dysfunction, gonadal and growth failure, osteoporosis, and adrenal insufficiency, affecting the quality of life of these patients. Thus, we aim to provide current knowledge and data about the epidemiology, pathogenesis, diagnosis, and management of endocrine disorders in β-thalassemia and SCD. We conducted a comprehensive review of the literature and examined the available data, mostly using the PubMed and Medline search engines for original articles. In the era of precision medicine, more studies investigating the potential role of genetic modifiers in the development of endocrinopathies in hemoglobinopathies are essential.
Topics: Humans; Iron; beta-Thalassemia; Quality of Life; Hemoglobinopathies; Anemia, Sickle Cell; Diabetes Mellitus
PubMed: 38003451
DOI: 10.3390/ijms242216263 -
Transfusion and Apheresis Science :... Feb 2021Beta hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia (BT) are the most common monogenic diseases worldwide. Both diseases are associated with... (Review)
Review
Beta hemoglobinopathies such as sickle cell disease (SCD) and β-thalassemia (BT) are the most common monogenic diseases worldwide. Both diseases are associated with significant morbidity and mortality. Because patients require lifelong follow-up and care, it also poses a serious burden in health services. Blood transfusions and/or drug therapy ameliorate the signs and symptoms of the disorders but are not curative. Allogeneic hematopoietic cell transplantation (HCT) is currently the only cure but it has several limitations including the paucity of human leukocyte antigen-matched related donors and a high risk of adverse events. Recent advances in hematopoietic stem cell based-gene therapy has made autologous HCT (auto-HCT) a reality. Clinical trials are underway using different gene transfer vectors and cassettes. Data obtained so far with a short-term follow-up has been very encouraging. Patients with SCD engrafted, had sustained production of the transgene and a decreased number of vaso-occlusive crises. Patients with BT were able to decrease the amount of transfusions required or stop transfusions all together. Adverse events observed were mostly associated with the myeloablative conditioning regimen. Long term data on gene persistence and toxicities are still needed. This review focuses on the current state of auto-HCT with gene therapy for SCD and BT. Current clinical trials and their outcome results are summarized.
Topics: Genetic Therapy; Hematopoietic Stem Cell Transplantation; Hemoglobinopathies; Humans; Transplantation Conditioning
PubMed: 33461919
DOI: 10.1016/j.transci.2021.103061 -
Clinica Chimica Acta; International... Jan 2024Hemoglobin (Hb) abnormalities, such as thalassemia and structural Hb variants, are among the most prevalent inherited diseases and are associated with significant... (Review)
Review
Hemoglobin (Hb) abnormalities, such as thalassemia and structural Hb variants, are among the most prevalent inherited diseases and are associated with significant mortality and morbidity worldwide. However, there were not comprehensive reviews focusing on different clinical analytical techniques, research methods and artificial intelligence (AI) used in clinical screening and research on hemoglobinopathies. Hence the review offers a comprehensive summary of recent advancements and breakthroughs in the detection of aberrant Hbs, research methods and AI uses as well as the present restrictions anddifficulties in hemoglobinopathies. Recent advances in cation exchange high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), isoelectric focusing (IEF), flow cytometry, mass spectrometry (MS) and polymerase chain reaction (PCR) etc have allowed for the definitive detection by using advanced AIand portable point of care tests (POCT) integrating with smartphone microscopic classification, machine learning (ML) model, complete blood counts (CBC), imaging-based method, speedy immunoassay, and electrochemical-, microfluidic- and sensing-related platforms. In addition, to confirm and validate unidentified and novel Hbs, highly specialized genetic based techniques like PCR, reverse transcribed (RT)-PCR, DNA microarray, sequencing of genomic DNA, and sequencing of RT-PCR amplified globin cDNA of the gene of interest have been used. Hence, adequate utilization and improvement of available diagnostic and screening technologies are important for the control and management of hemoglobinopathies.
Topics: Humans; Hemoglobins, Abnormal; Artificial Intelligence; Hemoglobinopathies; Thalassemia; Hemoglobins; Isoelectric Focusing; Chromatography, High Pressure Liquid
PubMed: 38030031
DOI: 10.1016/j.cca.2023.117685