-
Clinical Radiology Jul 2023Sickle cell disease (SCD) is an autosomal recessive haemoglobinopathy, which manifests as multisystem ischaemia and infarction, as well as haemolytic anaemia. The... (Review)
Review
Sickle cell disease (SCD) is an autosomal recessive haemoglobinopathy, which manifests as multisystem ischaemia and infarction, as well as haemolytic anaemia. The morphological changes of red blood cells (RBCs) that promote ischaemia/infarction as the main multi-systemic manifestation, with associated vasculopathy, may also lead to haemorrhage and fat embolisation. Bone infarctions, whether of the skull or spine, are relatively common with subsequent increased infectious susceptibility. We present a broad spectrum of brain and spine imaging findings of SCD from a level III paediatric hospital in Lisbon, between 2010 and 2022. Our aim is to highlight brain and spine imaging findings from a serial review of multiple patients with SCD and respective neuroimaging characterisation.
Topics: Humans; Child; Anemia, Sickle Cell; Neuroimaging; Brain; Vascular Diseases; Head
PubMed: 36935257
DOI: 10.1016/j.crad.2023.02.013 -
The Lancet. Haematology Sep 2019
Topics: Animals; CRISPR-Cas Systems; Carrier Proteins; Gene Editing; Hemoglobinopathies; Humans; Mice; Nuclear Proteins; Repressor Proteins
PubMed: 31471004
DOI: 10.1016/S2352-3026(19)30169-3 -
Blood Jan 2023
Topics: Humans; Anemia, Sickle Cell; Hemoglobinopathies; Glycolipids
PubMed: 36633883
DOI: 10.1182/blood.2022018075 -
Hemoglobin Nov 2023The thalassemia issue is a growing worldwide health concern that anticipates the number of patients suffering from the disease will soon increase significantly. Patients... (Review)
Review
The thalassemia issue is a growing worldwide health concern that anticipates the number of patients suffering from the disease will soon increase significantly. Patients with β-thalassemia intermedia (β-TI) manifest mild to intermediate levels of anemia, which is a reason for it to be clinically located between thalassemia minor and β-thalassemia major (β-TM). Notably, the determination of the actual rate of β-TI is more complicated than β-TM. The leading cause of this illness could be partial repression of β-globin protein production; accordingly, the rate of β-globin gene repression is different in patients, and the gene repression intensity creates a different clinical status. This review article provides an overview of functional mechanisms, advantages, and disadvantages of the classic to latest new treatments for this group of patients, depending on the disease severity divided into the typical management strategies for patients with β-TI such as fetal hemoglobin (Hb) induction, splenectomy, bone marrow transplantation (BMT), transfusion therapy, and herbal and chemical iron chelators. Recently, novel erythropoiesis-stimulating agents have been added. Novel strategies are subclassified into molecular and cellular interventions. Genome editing is one of the efficient molecular therapies for improving hemoglobinopathies, especially β-TI. It encompasses high-fidelity DNA repair (HDR), base and prime editing, clustered regularly interspaced short palindromic repeats (CRISPR)/Cas9 procedure, nuclease-free strategies, and epigenetic modulation. In cellular interventions, we mentioned the approach pattern to improve erythropoiesis impairments in translational models and patients with β-TI that involve activin II receptor traps, Janus-associated kinase 2 (JAK2) inhibitors, and iron metabolism regulation.
Topics: Humans; Thalassemia; beta-Thalassemia; Iron; Iron Chelating Agents; beta-Globins
PubMed: 37325871
DOI: 10.1080/03630269.2022.2158099 -
British Journal of Haematology Jan 2024For this paper, cases reported formally and anecdotally to the authors in their screening and diagnostic roles have been selected to demonstrate areas where errors have... (Review)
Review
For this paper, cases reported formally and anecdotally to the authors in their screening and diagnostic roles have been selected to demonstrate areas where errors have occurred, and caution should be exercised. The cases demonstrate that it is vital that the performance and limitations of the techniques used, along with the phenotypic presentation of cases where haemoglobin variants and/or thalassaemias are coinherited are understood by those performing result interpretation. Those who deliver the service as well as those who receive reports and give results and counselling should be aware of the complexity of the topic.
Topics: Humans; Hemoglobinopathies; Thalassemia; Anemia, Sickle Cell
PubMed: 37932940
DOI: 10.1111/bjh.19181 -
Blood Reviews May 2024Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point... (Review)
Review
Recent advancements in gene editing illuminate new potential therapeutic approaches for Sickle Cell Disease (SCD), a debilitating monogenic disorder caused by a point mutation in the β-globin gene. Despite the availability of several FDA-approved medications for symptomatic relief, allogeneic hematopoietic stem cell transplantation (HSCT) remains the sole curative option, underscoring a persistent need for novel treatments. This review delves into the growing field of gene editing, particularly the extensive research focused on curing haemoglobinopathies like SCD. We examine the use of techniques such as CRISPR-Cas9 and homology-directed repair, base editing, and prime editing to either correct the pathogenic variant into a non-pathogenic or wild-type one or augment fetal haemoglobin (HbF) production. The article elucidates ways to optimize these tools for efficacious gene editing with minimal off-target effects and offers insights into their effective delivery into cells. Furthermore, we explore clinical trials involving alternative SCD treatment strategies, such as LentiGlobin therapy and autologous HSCT, distilling the current findings. This review consolidates vital information for the clinical translation of gene editing for SCD, providing strategic insights for investigators eager to further the development of gene editing for SCD.
Topics: Humans; Gene Editing; CRISPR-Cas Systems; Anemia, Sickle Cell; Hemoglobinopathies; Fetal Hemoglobin
PubMed: 38493007
DOI: 10.1016/j.blre.2024.101185 -
AANA Journal Apr 2023This case study examines a patient undergoing an elective procedure who had a past medical history of Hemoglobin Louisville and presented with baseline oxygen saturation...
This case study examines a patient undergoing an elective procedure who had a past medical history of Hemoglobin Louisville and presented with baseline oxygen saturation levels (SpO) in the 80s as measured by noninvasive pulse oximetry. It presents the anesthetic provided, a brief review of physiology, and a discussion pertaining to this particular genetic mutation. Understanding the physiological implications of these types of hemoglobinopathies and their anesthetic management is key to managing patients' care throughout the perioperative period. With new hemoglobin variants continuing to emerge, reviewing some of the rare hemoglobinopathies is prudent to support the anesthesia community in their assessment and care of patients who present with unexpectedly low SPO.
Topics: Humans; Hemoglobins, Abnormal; Hemoglobinopathies; Oximetry; Anesthesia; Oxygen
PubMed: 36951838
DOI: No ID Found -
Hemoglobin Jul 2022Disease registries can be extremely powerful evidence generating tools while providing a central meeting point for all implicated stakeholders, facilitating their... (Review)
Review
Disease registries can be extremely powerful evidence generating tools while providing a central meeting point for all implicated stakeholders, facilitating their networking and interaction. Registries can play a major role in addressing the challenges that the care of thalassemia patients is currently facing. By collecting updated and representative data on disease burden, features, management and outcomes at local, national, regional and global level, thalassemia registries can allow the evaluation and bench marking of provided healthcare services, the detection of unmet clinical needs and the identification of inequalities in healthcare delivery. A total of 17 thalassemia registries has been in place since 1984, being characterized by heterogeneity and incomplete geographic coverage. Representativeness, interoperability, harmonization, quality assurance and sustainability are important features that thalassemia registries should pursue. The Thalassaemia International Federation (TIF) aims at promoting the coordination and collaboration in existing thalassemia registries and the establishment of new ones, with a particular focus on areas of emerging economies. In this regard, TIF has undertaken the design, development and implementation of a web-based platform to host a global thalassemia registry.
Topics: Humans; Thalassemia; Registries
PubMed: 36000583
DOI: 10.1080/03630269.2022.2099285 -
Hemoglobin Jan 2022Bangladesh is a country with a population of 160 million with a gross national income per capita of US$1580.00. The major health problems in Bangladesh include acute... (Review)
Review
Bangladesh is a country with a population of 160 million with a gross national income per capita of US$1580.00. The major health problems in Bangladesh include acute respiratory infection, pneumonia, dengue fever, malaria and water-borne diseases. The health care system in Bangladesh is divided into primary secondary and tertiary levels, with each level having their own breakdown of available hospital beds and other treatment facilities. Thalassemia is a major health problem in Bangladesh. There are two types of thalassemia in Bangladesh: β-thalassemia (β-thal) and Hb E (: c.79G>A)/β-thal, with the prevalence rate of β-thal trait being 4.1% and Hb E trait 6.1%. This study discusses spectrum types of thalassemia and hemoglobinopathies in Bangladesh and the types of carrier detection. The distribution of common mutations of thalassemia are also discussed and the distribution frequencies of genotypes and alleles of β-thal and Hb E patients are also compared. Additionally, we also conducted a study of the spectrum of thalassemia using high performance liquid chromatography (HPLC) of the tribal populations and analyzed the findings in our discussion. The results of these studies show that the phenotypic and genotypic presentation in Bangladesh is highly diverse. To properly understand this, we have to conduct an epidemiological survey of the population. Furthermore, there also has to be improvement on the awareness of thalassemia among the population to properly equip themselves to survive this disease.
Topics: Asia; Bangladesh; Hemoglobinopathies; Humans; Mutation; alpha-Thalassemia; beta-Thalassemia
PubMed: 35950585
DOI: 10.1080/03630269.2021.2008957 -
Biomedica : Revista Del Instituto... Mar 2024Introduction. The first neonatal screening program in Colombia – PREGEN – was set up in the medical private sector of Bogotá in 1988. We report the results from...
Introduction. The first neonatal screening program in Colombia – PREGEN – was set up in the medical private sector of Bogotá in 1988. We report the results from recent years that, given the scarcity of similar information in our country, may help estimate the frequency of the evaluated neonatal disorders and which ones should be included in the neonatal screening programs in our country. Objective. To describe the results of PREGEN´s newborn screening program between 2006 and 2019. Materials and methods. We analyzed databases and other informative documents preserved in PREGEN from the 2006-2019 period. Results. One in every 164 newborns screened in our program had an abnormal hemoglobin variant, and one in every 194 carried some hemoglobin S variant. Glucose-6- phosphate dehydrogenase deficiency and congenital hypothyroidism are next as the more common disorders. Conclusions. Abnormal hemoglobin causes the most frequent monogenic disorder in the world. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymopathy affecting nearly 400 million individuals worldwide. Since both disorders are more common in people of African descent and confer some resistance to malaria, we believe that screening for both disorders may be more relevant in the areas with African ancestry in our country.
Topics: Colombia; Neonatal Screening; Humans; Infant, Newborn; Glucosephosphate Dehydrogenase Deficiency; Private Sector; Congenital Hypothyroidism; Anemia, Sickle Cell; Hemoglobinopathies
PubMed: 38648350
DOI: 10.7705/biomedica.6911