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Orphanet Journal of Rare Diseases Jul 2023Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical... (Clinical Trial)
Clinical Trial
BACKGROUND
Inherited blood disorders affect 7% of the population worldwide, with higher prevalences in countries in the "thalassemia belt," which includes Bangladesh. Clinical management options for severely affected individuals are expensive; thus, targeted government policies are needed to support prevention and treatment programs. In Bangladesh, there is a lack of data, in particular community-based estimates, to determine population prevalence. This study aims to estimate the prevalence of a wide range of hemoglobinopathies and their associations with anemia in a community-based sample of women and young children in rural Sylhet, Bangladesh.
METHODS
Capillary blood samples from 900 reproductive-aged women and 395 children (aged 6-37 months) participating in the Food and Agricultural Approaches to Reducing Malnutrition (FAARM) trial in two sub-districts of Habiganj, Sylhet Division, Bangladesh were analyzed for alpha thalassemia, beta thalassemia, and other hemoglobinopathies. We examined the association of each inherited blood disorder with hemoglobin concentration and anemia using linear and logistic regression.
RESULTS
We identified at least one inherited blood disorder in 11% of women and 10% of children. Alpha thalassemia was most prevalent, identified in 7% of women and 5% of children, followed by beta thalassemia and hemoglobin E in 2-3%. We also identified cases of hemoglobin S and hemoglobin D in this population. Having any of the identified inherited blood disorders was associated with lower hemoglobin values among non-pregnant women, largely driven by alpha and beta thalassemia. Pregnant women with beta thalassemia were also more likely to have lower hemoglobin concentrations. Among children, we found weak evidence for a relationship between hemoglobinopathy and lower hemoglobin concentrations.
CONCLUSIONS
We found a high prevalence of alpha thalassemia among both women and children in rural Sylhet, Bangladesh-higher than all other identified hemoglobinopathies combined. Community-based estimates of alpha thalassemia prevalence in Bangladesh are scarce, yet our findings suggest that alpha thalassemia may comprise the majority of inherited blood disorders in some regions of the country. We recommend that future research on inherited blood disorders in Bangladesh include estimates of alpha thalassemia in their reporting for public health awareness and to facilitate couples counseling.
Topics: Adult; Child, Preschool; Female; Humans; Infant; alpha-Thalassemia; Bangladesh; beta-Thalassemia; Hemoglobinopathies; Prevalence
PubMed: 37468973
DOI: 10.1186/s13023-023-02821-3 -
Cells May 2024The β-thalassemias are inherited genetic disorders affecting the hematopoietic system. In β-thalassemias, more than 350 mutations of the adult gene cause the low or... (Review)
Review
The β-thalassemias are inherited genetic disorders affecting the hematopoietic system. In β-thalassemias, more than 350 mutations of the adult gene cause the low or absent production of adult hemoglobin (HbA). A clinical parameter affecting the physiology of erythroid cells is the excess of free α-globin. Possible experimental strategies for a reduction in excess free α-globin chains in β-thalassemia are CRISPR-Cas9-based genome editing of the gene, forcing "de novo" HbA production and fetal hemoglobin (HbF) induction. In addition, a reduction in excess free α-globin chains in β-thalassemia can be achieved by induction of the autophagic process. This process is regulated by the Unc-51-like kinase 1 () gene. The interplay with the PI3K/Akt/TOR pathway, with the activity of the α-globin stabilizing protein (AHSP) and the involvement of microRNAs in autophagy and gene expression, is presented and discussed in the context of identifying novel biomarkers and potential therapeutic targets for β-thalassemia.
Topics: Humans; beta-Thalassemia; Autophagy; Autophagy-Related Protein-1 Homolog; Animals; Signal Transduction; Gene Editing; Intracellular Signaling Peptides and Proteins
PubMed: 38891049
DOI: 10.3390/cells13110918 -
Experimental Biology and Medicine... Aug 2023Sickle cell disease (SCD) is an inherited hemoglobinopathy in which affected hemoglobin polymerizes under hypoxic conditions resulting in red cell distortion and chronic... (Review)
Review
Sickle cell disease (SCD) is an inherited hemoglobinopathy in which affected hemoglobin polymerizes under hypoxic conditions resulting in red cell distortion and chronic hemolytic anemia. SCD affects millions of people worldwide, primarily in Sub-Saharan Africa and the Indian subcontinent. Due to vaso-occlusion of sickled red cells within the microvasculature, SCD affects virtually every organ system and causes significant morbidity and early mortality. The neurological complications of SCD are particularly devastating and diverse, ranging from overt stroke to covert cerebral injury, including silent cerebral infarctions and blood vessel tortuosity. However, even individuals without evidence of neuroanatomical changes in brain imaging have evidence of cognitive deficits compared to matched healthy controls likely due to chronic cerebral hypoxemia and neuroinflammation. In this review, we first examined the biological contributors to SCD-related neurological complications and then discussed the equally important socioenvironmental contributors. We then discuss the evidence for neuroprotection from the two primary disease-modifying therapies, chronic monthly blood transfusions and hydroxyurea, and end with several experimental therapies designed to specifically target these complications.
Topics: Humans; Anemia, Sickle Cell; Stroke; Hydroxyurea; Blood Transfusion; Cognitive Dysfunction
PubMed: 37688519
DOI: 10.1177/15353702231187646 -
Journal of Molecular Biology Apr 2024In humans, specific aberrations in β-globin results in sickle cell disease and β-thalassemia, symptoms of which can be ameliorated by increased expression of fetal... (Review)
Review
In humans, specific aberrations in β-globin results in sickle cell disease and β-thalassemia, symptoms of which can be ameliorated by increased expression of fetal globin (HbF). Two recent CRISPR-Cas9 screens, centered on ∼1500 annotated sequence-specific DNA binding proteins and performed in a human erythroid cell line that expresses adult hemoglobin, uncovered four groups of candidate regulators of HbF gene expression. They are (1) members of the nucleosome remodeling and deacetylase (NuRD) complex proteins that are already known for HbF control; (2) seven C2H2 zinc finger (ZF) proteins, including some (ZBTB7A and BCL11A) already known for directly silencing the fetal γ-globin genes in adult human erythroid cells; (3) a few other transcription factors of different structural classes that might indirectly influence HbF gene expression; and (4) DNA methyltransferase 1 (DNMT1) that maintains the DNA methylation marks that attract the MBD2-associated NuRD complex to DNA as well as associated histone H3 lysine 9 methylation. Here we briefly discuss the effects of these regulators, particularly C2H2 ZFs, in inducing HbF expression for treating β-hemoglobin disorders, together with recent advances in developing safe and effective small-molecule therapeutics for the regulation of this well-conserved hemoglobin switch.
Topics: Humans; Cell Line, Tumor; CYS2-HIS2 Zinc Fingers; DNA; DNA-Binding Proteins; Fetal Hemoglobin; gamma-Globins; Hemoglobinopathies; Repressor Proteins; Transcription Factors
PubMed: 37924864
DOI: 10.1016/j.jmb.2023.168343 -
Medicine Nov 2023Sickle cell anemia (SCA) is a severe form of sickle cell disease that primarily affects black populations and individuals in tropical countries. This condition causes... (Review)
Review
Sickle cell anemia (SCA) is a severe form of sickle cell disease that primarily affects black populations and individuals in tropical countries. This condition causes significant morbidity and mortality and leads to a range of psychosocial challenges. A preliminary search was conducted on Ovid Medline and public databases with a combination of Medical Subject Headings keywords, resulting in 368 articles. The articles were screened based on the selection criteria in a nonsystematic method by 3 researchers, and a narrative synthesis was done to analyze extracted data from selected peer-reviewed article. Mental disorders, sleep disturbances, interpersonal relationship challenges, stigmatization, and workplace discrimination were identified as significant contributors to the psychosocial distress experienced by individuals with SCA and their families. Depression and anxiety were prevalent among individuals with SCA, leading to poor treatment adherence, increased pain, and disruptions in various aspects of life. Sleep disturbances, including sleep-disordered breathing and sleepwalking, were also identified as significant contributors to poor sleep quality in SCA patients. Families of individuals with SCA also face challenges, including psychological stress, financial strain, and social disruption. Stigmatization is common, leading to misconceptions and discrimination. Workplace discrimination is prevalent, with a high unemployment rate among adult SCA patients. Comprehensive care is crucial to address these psychosocial issues. Early identification and intervention, comprehensive support programs, patient and family education, enhanced pain management strategies, and integration of mental health into clinical care are recommended. School-based support, research and advocacy, and community support groups are also important. By addressing these challenges through comprehensive care and support, healthcare professionals, policymakers, and society can reduce psychosocial distress and improve the lives of individuals with SCA.
Topics: Adult; Humans; Mental Disorders; Anxiety; Mental Health; Interpersonal Relations; Anemia, Sickle Cell
PubMed: 38013366
DOI: 10.1097/MD.0000000000036147 -
Kidney360 Jul 2023The underlying mechanisms of disease in sickle cell disease (SCD) contribute to a multifaceted nephropathy, commonly manifested as albuminuria. In severe SCD genotypes (...
The underlying mechanisms of disease in sickle cell disease (SCD) contribute to a multifaceted nephropathy, commonly manifested as albuminuria. In severe SCD genotypes ( e.g. , Hemoglobin SS [HbSS]), albuminuria and CKD are major predictors of mortality in this population. Therefore, the monitoring and management of renal function is an intrinsic part of comprehensive care in SCD. Management of nephropathy in SCD can be accomplished with SCD-directed therapies and/or CKD-directed therapies. In the past 5 years, novel disease-modifying and palliative therapies have been approved in SCD to target aspects of the disease, such as anemia, inflammation, and vasculopathy. Along with conventional hydroxyurea and chronic transfusion, l -glutamine, crizanlizumab, and voxelotor have all been shown to mitigate some adverse effect of SCD, and their effect on nephropathy is being investigated. CKD-directed therapies such as renin-angiotensin-aldosterone system blockers have long been used in SCD nephropathy; however, more complete long-term studies on benefits are needed. Given the effect of renal disease on survival, further assessment of the mechanisms and efficacy of these SCD-directed or CKD-directed therapeutic agents is essential.
Topics: Humans; Albuminuria; Anemia, Sickle Cell; Kidney; Hemoglobin, Sickle; Vascular Diseases; Renal Insufficiency, Chronic
PubMed: 37254256
DOI: 10.34067/KID.0000000000000162 -
Ethiopian Journal of Health Sciences Nov 2023Children with sickle cell anaemia have been reported to have potential risk of hypothyroidism from chronic blood transfusions and probable thyroid tissue ischaemia....
BACKGROUND
Children with sickle cell anaemia have been reported to have potential risk of hypothyroidism from chronic blood transfusions and probable thyroid tissue ischaemia. However, few studies on hypothyroidism status of children with sickle cell anaemia in Nigeria are available. The objective of this study was to determine the prevalence of hypothyroidism among children with sickle cell anaemia.
METHODS
A cross sectional study that assayed the thyroid hormones and thyroid stimulating hormone (TSH) of 71 children with sickle cell anaemia was conducted at Olabisi Onabanjo University Teaching Hospital Sagamu. Using age appropriate hormonal reference values, the subjects were classified into subclinical, primary and secondary hypothyroidism.
RESULTS
The mean serum TSH, Free T3, and Free T4 were comparable irrespective of age category (p > 0.05). No subject was identified to have low TSH value while 7.0% had high TSH value. Low free T3 was identified in 1.4% and 8.5% had high free T3 values. Low free T3 and free T4 were seen in 11.3% each of the subjects. The overall prevalence of primary, secondary and subclinical hypothyroidism was 0%, 0% and 4.2%, respectively.
CONCLUSION
Sub-clinical hypothyroidism does occur in Nigerian children with sickle cell anaemia. Routine screening for hypothyroidism is advocated in all children with sickle cell anaemia.
Topics: Humans; Anemia, Sickle Cell; Hypothyroidism; Child; Male; Cross-Sectional Studies; Female; Nigeria; Thyrotropin; Child, Preschool; Prevalence; Adolescent; Thyroxine; Triiodothyronine; Thyroid Hormones; Infant
PubMed: 38784480
DOI: 10.4314/ejhs.v33i6.6 -
Blood Advances Feb 2024Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia... (Meta-Analysis)
Meta-Analysis
Advancements in orally bioavailable iron chelators and MRI methods have improved life expectancy and reproductive potential in thalassemia major (TM) and thalassemia intermedia (TI). Pregnancy is associated with adverse maternal and neonatal outcomes, frequency of which has not been well delineated. This systematic review aims to provide risk estimates of maternal and fetal outcomes in TM and TI and explore pregnancy's impact on iron homeostasis. Fifteen studies (429 participants, 684 pregnancies) were included. Meta-analysis revealed a higher thrombosis risk in TI (3.7%) compared to TM (0.92%), unchanged from prepregnancy. Heart failure risks in the earlier years appeared similar (TM 1.6% vs TI 1.1%), and maternal mortality in TM was 3.7%, but with current management, these risks are rare. Gestational diabetes and pre-eclampsia occurred in 3.9% and 11.3% of TM pregnancies, respectively. Caesarean section rates were 83.9% in TM and 67% in TI. No significant difference in stillbirth, small for gestational age neonates, or preterm birth incidence between TM and TI was observed. In TM pregnancies, red cell requirements significantly increased (from 102 to 139 ml/kg/year, P = 0.001), and 70% of TI pregnancies required blood transfusions. As expected, increased transfusion alongside chelation cessation led to a significant increase in serum ferritin during pregnancy (TM by 1005 ng/mL; TI by 332 ng/mL, P < 0.0001). Deterioration in iron status was further reflected by an increase in liver iron concentration (from 4.6 to 11.9 mg/g dry weight, P < 0.0001), and myocardial T2-star (T2∗) magnetic resonance imaging decreased (from 36.2 ± 2.5 ms to 31.1 ms) during pregnancy. These findings emphasize the elevated maternal risk of iron-related cardiomyopathy during pregnancy and labor, stressing the importance of cardiac monitoring and postpartum chelation therapy resumption.
Topics: Humans; Infant, Newborn; Pregnancy; Female; beta-Thalassemia; Iron; Pregnancy Outcome; Cesarean Section; Premature Birth
PubMed: 38181780
DOI: 10.1182/bloodadvances.2023011636 -
Cell Transplantation 2024While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first... (Review)
Review
While exagamglogene autotemcel (Casgevy) and lovotibeglogene autotemcel (Lyfgenia) have been approved by the US Food and Drug Administration (FDA) as the first cell-based gene therapies for the treatment of patients 12 years of age and older with sickle cell disease (SCD), this treatment is not universally accessible. Allogeneic hematopoietic stem cell transplant (HSCT) has the potential to eradicate the symptoms of patients with SCD, but a significant obstacle in HSCT for SCD is the availability of suitable donors, particularly human leukocyte antigen (HLA)-matched related donors. Furthermore, individuals with SCD face an elevated risk of complications during stem cell transplantation due to SCD-related tissue damage, endothelial activation, and inflammation. Therefore, it is imperative to consider optimal conditioning regimens and investigate HSCT from alternative donors. This review encompasses information on the use of HSCT in patients with SCD, including the indications for HSCT, conditioning regimens, alternative donors, and posttransplant outcomes.
Topics: Humans; Anemia, Sickle Cell; Hematopoietic Stem Cell Transplantation; Transplantation Conditioning
PubMed: 38680015
DOI: 10.1177/09636897241246351 -
Blood Advances Oct 2023
Topics: Humans; Hydroxyurea; Anemia, Sickle Cell; Malaria
PubMed: 37815815
DOI: 10.1182/bloodadvances.2023010547