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BMC Pediatrics May 2024Sickle cell disease (SCD), a noncommunicable disease, has the greatest burden in sub-Saharan Africa. The majority of children (50-90%) with SCD die before their 5th...
BACKGROUND
Sickle cell disease (SCD), a noncommunicable disease, has the greatest burden in sub-Saharan Africa. The majority of children (50-90%) with SCD die before their 5th birthday, with approximately 150,000-300,000 annual SCD child deaths in Africa. In developed countries, newborn screening (NBS) has been shown to improve the survival of children with sickle cell disease, with under5 childhood mortality reduced tenfold due to interventions performed before the development of complications. Point -of-care tests have been developed for resource limited settings to expand NBS. The aim of this study was to determine the birth prevalence of sickle cell disease in Namibia using the HemoTypeSC™ point-of-care test.
METHODS
A cross-sectional descriptive study was carried out at Rundu Intermediate Hospital in the Kavango East Region. Two hundred and two (202) well newborns within 72 h of birth were recruited for the study from 22 February to the 23th March 2023. Descriptive statistics were used to compute the haemoglobin types of the study participants.
RESULTS
The majority of the participants (n = 105, 52%) were females, and (n = 97,48%) were males. The median age of the participants was 23 h (Q1, Q3; 11; 33),) with an age range of 2-98 h. Sickle cell trait was present in 9.4% of the screened newborns, no homozygous disease was detected, and 90.6% had Hb AA.
CONCLUSIONS
This study is the first to measure HbS gene carriage at birth using HemotypeSC point-of-care testing in Namibia. There was a moderate prevalence of sickle cell traits but no SCD. This baseline study may provide the foundation for larger epidemiological surveys to map HbS gene carriage in Namibia to provide evidence for policy makers to fashion appropriate SCD newborn screening services.
Topics: Humans; Anemia, Sickle Cell; Infant, Newborn; Cross-Sectional Studies; Namibia; Prevalence; Female; Male; Neonatal Screening; Point-of-Care Testing
PubMed: 38730340
DOI: 10.1186/s12887-024-04805-z -
The American Journal of Case Reports May 2024BACKGROUND Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide. Alpha-thalassemia and alpha-globin variants are...
BACKGROUND Thalassemia and hemoglobin (Hb) variants are the most common hereditary red blood cell disorders worldwide. Alpha-thalassemia and alpha-globin variants are caused by mutations of the alpha-globin genes (HBA2 and HBA1), resulting in impaired alpha-globin production and structurally abnormal globin, respectively. Clinical severity of alpha-thalassemia correlates with the number of affected alpha-globin genes, yielding a spectrum of clinical manifestations from mild to severe anemia. Routine diagnosis involves Hb analysis and PCR-based methods, yet identifying rare variants necessitates comprehensive clinical and hematologic laboratory data. The knowledge of phenotype and genotype correlation is useful for genetic counseling and treatment planning. CASE REPORT A 59-year-old Thai woman presented with chronic anemia. Her baseline Hb level ranged between 8.0 and 9.0 g/dL, with no history of transfusion. Physical examination showed mild pallor, without enlarged liver and spleen. Laboratory investigations showed microcytic, hypochromic anemia and abnormal Hb peak by Hb analysis (retention time 4.58 min by HPLC method). Common alpha-globin gene deletions, including the Southeast-Asian/Thai 3.7 kb and 4.2 kb deletions were tested using gap-PCR, with none of these deletions detected. Direct DNA sequencing revealed a compound heterozygosity of Hb Jax (HBA2: c.44G>C) and Hb Constant Spring (HBA2: c.427T>C). CONCLUSIONS Compound heterozygosity of Hb Jax and Hb Constant Spring results in microcytic anemia. Hb Jax can be identified by Hb analysis, and diagnosis can be confirmed by direct DNA sequencing method. Coinheritance of Hb Jax and alpha-globin variants should be considered in cases with microcytic anemia and a specific Hb peak seen in Hb chromatogram.
Topics: Female; Humans; Middle Aged; alpha-Globins; alpha-Thalassemia; Anemia, Hypochromic; Hemoglobins, Abnormal
PubMed: 38725231
DOI: 10.12659/AJCR.943560 -
Saudi Journal of Kidney Diseases and... Nov 2023Proteinuria is a manifestation of sickle cell anemia (SCA)-related renal disease and is a risk factor of renal impairment. Angiotensin-converting enzyme (ACE) inhibitors...
Proteinuria is a manifestation of sickle cell anemia (SCA)-related renal disease and is a risk factor of renal impairment. Angiotensin-converting enzyme (ACE) inhibitors have benefits, but their role in SCA remains undefined. This study aimed to assess the role of lisinopril, an ACE inhibitor, in reducing proteinuria in SCA patients. Thirty-five patients older than 15 years with known SCA (HbSS or HbS-β0) and a 24-h urinary protein level of 150 mg or more participated in this study. Urine was collected over 24 h to quantify proteinuria. The patients had a mean age of 28.5 ± 6.98 years. The median 24-h urinary protein before treatment was 0.3006 g and that after treatment was 0.150 g (P = 0.01). After a median follow-up of 38 months, 24-h urinary protein decreased in 27 (77%) patients and normalized in 18 (52%) patients. Urinary protein increased in 2 (6%) patients and remained stable (no change) in 6 (17%) patients. There was no significant difference in blood pressure (BP) before and after treatment. The average dose of lisinopril was 5 mg. Twenty patients were still on lisinopril at last follow-up. The reasons for stopping lisinopril included normalization of protein, noncompliance, adverse effects, and pregnancy. Lisinopril effectively reduced proteinuria in SCA patients, without significantly reducing BP. Only a few patients developed adverse effects, including coughing, dizziness, and diarrhea. It is unclear how long lisinopril should be continued and whether it can be stopped in patients with normalized urinary protein.
Topics: Humans; Lisinopril; Proteinuria; Female; Male; Angiotensin-Converting Enzyme Inhibitors; Anemia, Sickle Cell; Adult; Young Adult; Treatment Outcome; Time Factors; Blood Pressure; Adolescent
PubMed: 38725203
DOI: 10.4103/sjkdt.sjkdt_312_22 -
Haematologica May 2024Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal...
Continuous and differential improvement in worldwide access to hematopoietic cell transplantation: activity has doubled in a decade with a notable increase in unrelated and non-identical related donors.
Promoting access to and excellence in hematopoietic cell transplantation (HCT) by collecting and disseminating data on global HCT activities is one of the principal activities of the Worldwide Network for Blood and Marrow Transplantation, a non-Governmental organization in working relations with the World Health Organization. HCT activities are recorded annually by member societies, national registries and individual centers including indication, donor type (allogeneic/autologous), donor match and stem cell source (bone marrow/peripheral blood stem cells/cord blood). In 2018, 1,768 HCT teams in 89 countries (six WHO regions) reported 93,105 (48,680 autologous and 44,425 allogeneic) HCT. Major indications were plasma cell disorders and lymphoma for autologous, and acute leukemias and MDS/MPN for allogeneic HCT. HCT number increased from 48,709 in 2007. Notable increases were seen for autoimmune diseases in autologous and hemoglobinopathies in allogeneic HCT. The number of allogeneic HCT more than doubled with significant changes in donor match. While HCT from HLA identical siblings has seen only limited growth, HCT from non-identical related donors showed significant increase worldwide. Strongest correlation between economic growth indicator of gross national income/capita and HCT activity/ten million population was observed for autologous HCT (r=0.79). HCT from unrelated donors showed strong correlation (r=0.68), but only moderate correlation (r=0.51) was detected from related donors. The use of HCT doubled in about a decade worldwide at different speed and with significant changes regarding donor match as a sign of improved access to HCT worldwide. Although narrowing, significant gaps remain between developing and non-developing countries.
PubMed: 38721749
DOI: 10.3324/haematol.2024.285002 -
Molecular Therapy. Nucleic Acids Jun 2024β-Thalassemia is brought about by defective β-globin (HBB [hemoglobin subunit β]) formation and, in severe cases, requires regular blood transfusion and iron...
β-Thalassemia is brought about by defective β-globin (HBB [hemoglobin subunit β]) formation and, in severe cases, requires regular blood transfusion and iron chelation for survival. Genome editing of hematopoietic stem cells allows correction of underlying mutations as curative therapy. As potentially safer alternatives to double-strand-break-based editors, base editors (BEs) catalyze base transitions for precision editing of DNA target sites, prompting us to reclone and evaluate two recently published adenine BEs (ABEs; SpRY and SpG) with relaxed protospacer adjacent motif requirements for their ability to correct the common splice mutation. Nucleofection of ABE components as RNA into patient-derived CD34 cells achieved up to 90% editing of upstream sequence elements critical for aberrant splicing, allowing full characterization of the on-target base-editing profile of each ABE and the detection of differences in on-target insertions and deletions. In addition, this study identifies opposing effects on splice correction for two neighboring context bases, establishes the frequency distribution of multiple BE editing events in the editing window, and shows high-efficiency functional correction of for our ABEs, including at the levels of RNA, protein, and erythroid differentiation.
PubMed: 38706633
DOI: 10.1016/j.omtn.2024.102183 -
Molecular Biology Reports May 2024The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of...
BACKGROUND
The α-Major Regulatory Element (α-MRE), also known as HS-40, is located upstream of the α-globin gene cluster and has a crucial role in the long-range regulation of the α-globin gene expression. This enhancer is polymorphic and several haplotypes were identified in different populations, with haplotype D almost exclusively found in African populations. The purpose of this research was to identify the HS-40 haplotype associated with the 3.7 kb α-thalassemia deletion (-α3.7del) in the Portuguese population, and determine its ancestry and influence on patients' hematological phenotype.
METHODS AND RESULTS
We selected 111 Portuguese individuals previously analyzed by Gap-PCR to detect the presence of the -α3.7del: 50 without the -α3.7del, 34 heterozygous and 27 homozygous for the -α3.7del. The HS-40 region was amplified by PCR followed by Sanger sequencing. Four HS-40 haplotypes were found (A to D). The distribution of HS-40 haplotypes and genotypes are significantly different between individuals with and without the -α3.7del, being haplotype D and genotype AD the most prevalent in patients with this deletion in homozygosity. Furthermore, multiple correspondence analysis revealed that individuals without the -α3.7del are grouped with other European populations, while samples with the -α3.7del are separated from these and found more closely related to the African population.
CONCLUSION
This study revealed for the first time an association of the HS-40 haplotype D with the -α3.7del in the Portuguese population, and its likely African ancestry. These results may have clinical importance as in vitro analysis of haplotype D showed a decrease in its enhancer activity on α-globin gene.
Topics: Female; Humans; Male; alpha-Globins; alpha-Thalassemia; Black People; Gene Frequency; Genotype; Haplotypes; Portugal; Regulatory Sequences, Nucleic Acid; Sequence Deletion
PubMed: 38704770
DOI: 10.1007/s11033-024-09530-5 -
Medicine May 2024Sickle cell anemia (SCA), a hereditary hemoglobinopathy, is characterized by the presence of abnormal hemoglobin and has long been associated with a wide range of... (Review)
Review
Sickle cell anemia (SCA), a hereditary hemoglobinopathy, is characterized by the presence of abnormal hemoglobin and has long been associated with a wide range of complications. While much attention has been given to the condition hematological aspects, gastrointestinal complications, particularly diarrhea, have been relatively understudied and often overlooked. This publication delves into the management of gastrointestinal challenges, with a focus on diarrhea, in individuals living with SCA. The pathophysiology of SCA is intrinsically linked to gastrointestinal complications, and diarrhea is a common manifestation of this condition. This abstract publication outlines the key elements discussed in the full-length work, which includes the clinical presentation of diarrhea in these patients, the diagnostic tools used to evaluate the condition, and various management strategies to alleviate symptoms and enhance the overall quality of life for affected individuals. The paper emphasizes the importance of patient education, offering healthcare professionals valuable insights into how to inform and support patients in managing their conditions effectively. It also highlights the need for continued research to further our understanding of gastrointestinal challenges in SCA and to identify potential areas for future therapeutic interventions. Ultimately, the comprehensive management of diarrhea in individuals with SCA is vital for their overall well-being. This publication serves as a valuable resource for healthcare providers, researchers, and caregivers in addressing the gastrointestinal challenges that accompany SCA, ultimately working toward a better quality of life for those affected by this condition.
Topics: Humans; Anemia, Sickle Cell; Diarrhea; Quality of Life; Patient Education as Topic
PubMed: 38701274
DOI: 10.1097/MD.0000000000038075 -
Medicine May 2024β-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of β-pearl protein chains. This results in... (Review)
Review
β-Thalassemia is the world's number 1 single-gene genetic disorder and is characterized by suppressed or impaired production of β-pearl protein chains. This results in intramedullary destruction and premature lysis of red blood cells in peripheral blood. Among them, patients with transfusion-dependent β-thalassemia face the problem of long-term transfusion and iron chelation therapy, which leads to clinical complications and great economic stress. As gene editing technology improves, we are seeing the dawn of a cure for the disease, with its reduction of ineffective erythropoiesis and effective prolongation of survival in critically ill patients. Here, we provide an overview of β-thalassemia distribution and pathophysiology. In addition, we focus on gene therapy and gene editing advances. Nucleic acid endonuclease tools currently available for gene editing fall into 3 categories: zinc finger nucleases, transcription activator-like effector nucleases, and regularly interspaced short palindromic repeats (CRISPR-Cas9) nucleases. This paper reviews the exploratory applications and exploration of emerging therapeutic tools based on 3 classes of nucleic acid endonucleases in the treatment of β-thalassemia diseases.
Topics: beta-Thalassemia; Humans; Gene Editing; Genetic Therapy; CRISPR-Cas Systems; Transcription Activator-Like Effector Nucleases; Zinc Finger Nucleases
PubMed: 38701251
DOI: 10.1097/MD.0000000000038036 -
Cureus Apr 2024Sickle cell disease is the most common genetic hemoglobinopathy worldwide, characterized by a single-nucleotide mutation that predisposes to hemoglobin polymerization...
Sickle cell disease is the most common genetic hemoglobinopathy worldwide, characterized by a single-nucleotide mutation that predisposes to hemoglobin polymerization and erythrocyte sickling in hypoxic states. This report describes a 62-year-old male obese patient with a history of sickle cell disease, who presented with worsening nocturnal pain crises without any apparent triggering factor. A thorough evaluation at the outpatient department revealed obstructive sleep apnea. Airway obstruction or decreased respiratory effort during sleep may induce hypoventilation and hypoxia in the context of sleep-disordered breathing, with severe cardiopulmonary complications. Sleep-disordered breathing is considered common in children with sickle cell disease, but the prevalence in adults has not been sufficiently documented. Our patient responded favorably to treatment with continuous positive airway pressure during sleep, showing complete resolution of his symptoms. Timely diagnosis and management are fundamental to improve outcomes and prevent severe complications.
PubMed: 38699085
DOI: 10.7759/cureus.57462 -
Scientific Reports May 2024β-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to...
β-Thalassaemia is one of the most common genetic diseases worldwide. During the past few decades, life expectancy of patients has increased significantly owing to advance in medical treatments. Cognitive impairment, once has been neglected, has gradually become more documented. Cognitive impairment in β-thalassaemia patients is associated with natural history of the disease and socioeconomic factors. Herein, to determined effect of β-thalassaemia intrinsic factors, 22-month-old β-thalassaemia mouse was used as a model to assess cognitive impairment and to investigate any aberrant brain pathology in β-thalassaemia. Open field test showed that β-thalassaemia mice had decreased motor function. However, no difference of neuronal degeneration in primary motor cortex, layer 2/3 area was found. Interestingly, impaired learning and memory function accessed by a Morris water maze test was observed and correlated with a reduced number of living pyramidal neurons in hippocampus at the CA3 region in β-thalassaemia mice. Cognitive impairment in β-thalassaemia mice was significantly correlated with several intrinsic β-thalassaemic factors including iron overload, anaemia, damaged red blood cells (RBCs), phosphatidylserine (PS)-exposed RBC large extracellular vesicles (EVs) and PS-exposed medium EVs. This highlights the importance of blood transfusion and iron chelation in β-thalassaemia patients. In addition, to improve patients' quality of life, assessment of cognitive functions should become part of routine follow-up.
Topics: Animals; beta-Thalassemia; Cognitive Dysfunction; Mice; Hippocampus; Disease Models, Animal; Male; Neurons; Iron Overload; Extracellular Vesicles; Erythrocytes; Pyramidal Cells; Maze Learning
PubMed: 38698053
DOI: 10.1038/s41598-024-60459-y