ABSTRACT
BACKGROUND: Hemoglobinopathies, the most common inherited blood disorder, are frequently underdiagnosed. Early identification of carriers is important for genetic counseling of couples at risk. The aim of this study was to develop and validate a novel machine learning model on a multicenter data set, covering a wide spectrum of hemoglobinopathies based on routine complete blood count (CBC) testing. METHODS: Hemoglobinopathy test results from 10 322 adults were extracted retrospectively from 8 Dutch laboratories. eXtreme Gradient Boosting (XGB) and logistic regression models were developed to differentiate negative from positive hemoglobinopathy cases, using 7 routine CBC parameters. External validation was conducted on a data set from an independent Dutch laboratory, with an additional external validation on a Spanish data set (n = 2629) specifically for differentiating thalassemia from iron deficiency anemia (IDA). RESULTS: The XGB and logistic regression models achieved an area under the receiver operating characteristic (AUROC) of 0.88 and 0.84, respectively, in distinguishing negative from positive hemoglobinopathy cases in the independent external validation set. Subclass analysis showed that the XGB model reached an AUROC of 0.97 for ß-thalassemia, 0.98 for α0-thalassemia, 0.95 for homozygous α+-thalassemia, 0.78 for heterozygous α+-thalassemia, and 0.94 for the structural hemoglobin variants Hemoglobin C, Hemoglobin D, Hemoglobin E. Both models attained AUROCs of 0.95 in differentiating IDA from thalassemia. CONCLUSIONS: Both the XGB and logistic regression model demonstrate high accuracy in predicting a broad range of hemoglobinopathies and are effective in differentiating hemoglobinopathies from IDA. Integration of these models into the laboratory information system facilitates automated hemoglobinopathy detection using routine CBC parameters.
Subject(s)
Hemoglobinopathies , Machine Learning , Humans , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , Hemoglobinopathies/blood , Retrospective Studies , Blood Cell Count , Adult , Female , Male , Logistic Models , ROC CurveABSTRACT
Haemoglobin disorders represent a heterogeneous group of inherited conditions that involve at least one genetic abnormality in one or more of the globin chains, resulting in changes in the structure, function, and/or amount of haemoglobin molecules, which are very important for their related clinical aspects. Detecting and characterizing these disorders depends primarily on laboratory methods that employ traditional approaches and, when necessary, newer methodologies essential for solving a number of diagnostic challenges. This review provides an overview of key laboratory techniques in the diagnosis of haemoglobinopathies, focusing on the challenges, advancements, and future directions in this field. Moreover, many haemoglobinopathies are benign and clinically silent, but it is not uncommon to find unexpected variants during routine laboratory tests. The present work reported a rare and clinically interesting case of identification of haemoglobin fractions in an adult man by the determination of glycated haemoglobin (HbA1c) during a routine laboratory assessment, highlighting how the correct use of laboratory data can modify and improve the patient's clinical management.
Subject(s)
Hemoglobinopathies , Molecular Diagnostic Techniques , Humans , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , Hemoglobinopathies/blood , Molecular Diagnostic Techniques/methods , Hemoglobins/genetics , Hemoglobins/analysis , Male , Glycated Hemoglobin/analysis , Hemoglobins, Abnormal/geneticsABSTRACT
In this report, we describe a 6-year-old girl with a medical history of pallor, mild icterus, anemia, blood transfusion and abnormal hemoglobin variant analysis on capillary electrophoresis. She was referred for further analysis. DNA sequencing of the proband revealed a de novo mutation in Codon 88 (CTG > CCG) of the ß-globin gene (HBB: c.266T > C) in a heterozygous state compatible with hemoglobin Santa Ana, an unstable hemoglobin. This is the first case of Hb Santa Ana from Iran associated with moderate to severe anemia who underwent splenectomy with clinical improvement.
Subject(s)
Hemoglobins, Abnormal , beta-Globins , Humans , Female , Hemoglobins, Abnormal/genetics , Child , Iran , beta-Globins/genetics , Mutation , Splenectomy , Hemoglobinopathies/diagnosis , Hemoglobinopathies/genetics , Hemoglobinopathies/bloodABSTRACT
OBJECTIVES: Hemoglobinopathies, including thalassemia and hemoglobin (Hb) variants, are common hematological disorders in tropical countries. Accurate and precise separation of hemoglobin types and reliable quantitation are necessary for differential diagnosis of these disorders. METHODS: We have evaluated the analytical performances of premier resolution-high-performance liquid chromatography (PR-HPLC; Trinity Biotech, Co. Wicklow, Ireland) to assist in the presumptive diagnosis of thalassemia and Hb variants commonly found in Southeast Asian countries. HbA0, HbA2, HbE, and HbF levels were separated and quantified in 120 blood samples from unrelated adult subjects and compared with those analyzed by capillary zone electrophoresis (CZE; CAPILLARYS™ 2, Sebia, Norcross, GA, US). The Hb analysis patterns of Hb variants obtained from the PR-HPLC system were also compared to those obtained from HPLC (VARIANT II, ß-thalassemia Short Program, Bio-Rad, Laboratories, Hercules, CA, US) and CZE systems. RESULTS: The PR-HPLC had excellent precision with a coefficient of variation (CV) for HbA2 quantitation of 3.8â¯% within-run and 5.2â¯% between-run. The levels of HbA2/E quantified by the PR-HPLC system correlated well with those of the CZE system (r=0.997). In addition, thalassemia interpretation results obtained from the PR-HPLC and the CZE showed 100â¯% agreement. Moreover, chromatograms of the PR-HPLC were also comparable to those of VII-HPLC and CAP2-CZE electropherograms. CONCLUSIONS: The PR-HPLC system would be applicable to diagnose common forms of thalassemia and Hb variants in Southeast Asia.
Subject(s)
Electrophoresis, Capillary , Humans , Chromatography, High Pressure Liquid/methods , Electrophoresis, Capillary/methods , Hemoglobins, Abnormal/analysis , Hemoglobin A2/analysis , Hemoglobin E/analysis , Hemoglobinopathies/diagnosis , Hemoglobinopathies/blood , Fetal Hemoglobin/analysis , AdultABSTRACT
Haploinsufficiency for the erythroid-specific transcription factor KLF1 is associated with hereditary persistence of fetal hemoglobin (HPFH). Increased HbF ameliorates the symptoms of ß-hemoglobinopathies and downregulation of KLF1 activity has been proposed as a potential therapeutic strategy. However, the feasibility of this approach has been challenged by the observation that KLF1 haploinsufficient individuals with the same KLF1 variant, within the same family, display a wide range of HbF levels. This phenotypic variability is not readily explained by co-inheritance of known HbF-modulating variants in the HBB, HBS1L-MYB and/or BCL11A loci. We studied cultured erythroid progenitors obtained from Maltese individuals in which KLF1 p.K288X carriers display HbF levels ranging between 1.3 and 12.3% of total Hb. Using a combination of gene expression analysis, chromatin accessibility assays and promoter activity tests we find that variation in expression of the wildtype KLF1 allele may explain a significant part of the variability in HbF levels observed in KLF1 haploinsufficiency. Our results have general bearing on the variable penetrance of haploinsufficiency phenotypes and on conflicting interpretations of pathogenicity of variants in other transcriptional regulators such as EP300, GATA2 and RUNX1.
Subject(s)
Epigenesis, Genetic , Epigenome , Epigenomics , Erythroblasts/metabolism , Haploinsufficiency , Hemoglobinopathies/genetics , Kruppel-Like Transcription Factors/genetics , Cells, Cultured , Chromatin Immunoprecipitation Sequencing , Erythroblasts/pathology , Erythropoiesis/genetics , Fetal Hemoglobin/genetics , Fetal Hemoglobin/metabolism , Genetic Predisposition to Disease , Hemoglobinopathies/blood , Hemoglobinopathies/diagnosis , Humans , Kruppel-Like Transcription Factors/metabolism , Malta , Penetrance , Phenotype , Primary Cell Culture , RNA-SeqABSTRACT
We describe presenting features, treatment strategies, and follow-up events involving 41 patients (median age 39 years, range 1-81; 54% males) with high oxygen affinity (HOA) hemoglobinopathy-associated erythrocytosis, seen at our institution (1973-2020). Thirty-four (83%) patients carried ß-chain (13 Malmo, 4 Olympia, 3 San Diego, 2 Wood) and 7 (17%) α-chain (4 Dallas and one each Columbia-Missouri, Jackson, and Wayne) variants. Median (range) hemoglobin (Hgb)/hematocrit (Hct), serum erythropoietin and p50 were 18 g/dL/52.9% (16-21.9/48-66), 10.4 mIU (4-36.3), and 20 mmHg (12-25), respectively. Family history was documented in 24 patients and history of thrombosis in two (5%). Treatment included phlebotomy in 23 and antiplatelet therapy in 21 patients. At a median follow-up of 10 years, 23 (56%) patients reported one or more symptoms that were thought to be related to their increased Hct while thrombosis was documented in 10 (24%) patients. Neither Hgb/Hct level nor active phlebotomy showed a significant correlation with either thrombotic or nonthrombotic symptoms (p > .1 in all instances). Among 23 pregnancies recorded, 78% resulted in live births and no fetal loss was attributed to erythrocytosis. The current study does not implicate Hgb/Hct level as a major contributor of morbidity in HOA hemoglobinopathy-associated erythrocytosis and suggests limited therapeutic value for phlebotomy.
Subject(s)
Hemoglobinopathies/complications , Polycythemia/etiology , Adult , Aged , Aged, 80 and over , Child , Disease Management , Female , Hemoglobinopathies/blood , Hemoglobinopathies/therapy , Humans , Infant , Male , Middle Aged , Oxygen/blood , Phlebotomy , Platelet Aggregation Inhibitors/therapeutic use , Polycythemia/blood , Polycythemia/therapy , Retrospective Studies , Young AdultABSTRACT
BACKGROUND: : HPLC is one of the most important tools for accurate diagnosis of hemoglobinopathies and thalassemias. The advantage of the HPLC system is the excellent resolution, reproducibility &quantification of several normal and abnormal hemoglobin. RESULTS: BIO RAD Variant II analyzer was used. Sickle cell syndromes including double heterozygous states accounted for 56.13% of total cases. HbSS, HbS/ß0-th, HbS/ß+-th ß-thal trait comprises 29%, 6.5%, 5.1%& 10% of total cases respectively with mean MCV (fl) = 84, 68,71,64 respectively. The Mean HbA2 for ß-thal trait, HbE trait &HbE-ß thal showed 5.1 ± 1.1, 19 ± 9 & 24 ± 8 respectively. HbF is increased in 8.6% case (excluding SC syndromes & ß-thal disorders), of these 5.5% were infants & 12 cases of Aplastic Anemias. Peak P2 >7% (2.4% cases) was seen in uncontrolled diabetes mellitus which on quantification showed HbA1C = 8 ± 2.1 mmol/L. DISCUSSION: : HPLC in correlation with CBC parameters & family studies can aid in the diagnosis of majority of Hemoglobinopathies and thalassemic syndrome. The CBC & HPLC parameters of the present study are in good correlation with the research conducted by Tejinder Sing, RiouJ & Alla Joutovsky. Present study showed HPLC comprehensively characterizing HbS, A, A2, F, S, C, D from each other & was also applicable for the quantification of HbA1c for the monitoring of Diabetes Mellitus. CONCLUSION: : The merits of HPLC are small quantity of sample required, economical, less TAT, accurate categorization of HbS, HbA2 & F. But one has to be aware of the limitations and problems associated with this method due to variant hemoglobin within the same retention windows. The present findings show HPLC as an excellent & powerful diagnostic tool for the direct identification of hemoglobin variants with a high degree of precision in the quantification of normal and abnormal hemoglobin fractions.
Subject(s)
Chromatography, High Pressure Liquid/methods , Chromatography, High Pressure Liquid/standards , Hemoglobinopathies/diagnosis , Hemoglobins, Abnormal/analysis , Thalassemia/diagnosis , Chromatography, High Pressure Liquid/economics , Hemoglobinopathies/blood , Humans , Phenotype , Reproducibility of Results , Retrospective Studies , Syndrome , Thalassemia/bloodSubject(s)
Anemia, Hemolytic/blood , Erythrocytes, Abnormal/ultrastructure , Hemoglobinopathies/blood , Hemoglobins, Abnormal/genetics , Multiple Organ Failure/blood , Physical Exertion , Anemia, Hemolytic/etiology , Anemia, Hemolytic/genetics , Anemia, Hemolytic/therapy , Autoantibodies/immunology , Cell Nucleus/ultrastructure , Dehydration/blood , Dehydration/etiology , Erythrocyte Inclusions/ultrastructure , Erythrocyte Transfusion , Fatal Outcome , Heart Valve Diseases/complications , Hemoglobinopathies/complications , Hemoglobinopathies/genetics , Humans , Isoantibodies/immunology , Male , Multiple Organ Failure/etiology , Shock, Cardiogenic/etiologyABSTRACT
For decades, various strategies have been proposed to solve the enigma of hemoglobinopathies, especially severe cases. However, most of them seem to be lagging in terms of effectiveness and safety. So far, the most prevalent and promising treatment options for patients with ß-types hemoglobinopathies, among others, predominantly include drug treatment and gene therapy. Despite the significant improvements of such interventions to the patient's quality of life, a variable response has been demonstrated among different groups of patients and populations. This is essentially due to the complexity of the disease and other genetic factors. In recent years, a more in-depth understanding of the molecular basis of the ß-type hemoglobinopathies has led to significant upgrades to the current technologies, as well as the addition of new ones attempting to elucidate these barriers. Therefore, the purpose of this article is to shed light on pharmacogenomics, gene addition, and genome editing technologies, and consequently, their potential use as direct and indirect genome-based interventions, in different strategies, referring to drug and gene therapy. Furthermore, all the latest progress, updates, and scientific achievements for patients with ß-type hemoglobinopathies will be described in detail.
Subject(s)
Anemia, Sickle Cell/therapy , Hemoglobinopathies/therapy , beta-Globins/genetics , beta-Thalassemia/therapy , Anemia, Sickle Cell/genetics , Gene Editing/methods , Genetic Therapy/trends , Hemoglobinopathies/blood , Hemoglobinopathies/genetics , Humans , beta-Globins/therapeutic use , beta-Thalassemia/geneticsABSTRACT
OBJECTIVE: To describe two cases of unusual variants of sickle cell disease. CASE DESCRIPTION: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. COMMENTS: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.
Subject(s)
Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/genetics , Blood Protein Electrophoresis/methods , Hemoglobinopathies/genetics , Osteomyelitis/diagnosis , Administration, Intravenous , Administration, Oral , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/epidemiology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antisickling Agents/administration & dosage , Antisickling Agents/therapeutic use , Child , Female , Hemoglobinopathies/blood , Hemoglobinopathies/diagnosis , Heterozygote , Humans , Hydroxyurea/administration & dosage , Hydroxyurea/therapeutic use , Magnetic Resonance Imaging/methods , Male , Mass Screening/ethics , Mass Screening/standards , Osteomyelitis/drug therapy , Osteomyelitis/etiology , Pakistan/ethnology , Prevalence , Radiography/methods , Treatment OutcomeABSTRACT
PURPOSE OF REVIEW: This review summarizes the significant biophysical and rheological aspects of red blood cell physiology and pathophysiology in relation to recent advances in microfluidic biomarker assays and emerging targeted or curative intent therapies. RECENT FINDINGS: Alterations in red cell biophysical properties and blood rheology have been associated with numerous hematologic and circulatory disorders. Recent advances in biomarker assays enable effective assessment of these biophysical and rheological properties in normoxia or physiological hypoxia in a clinically meaningful way. There are emerging targeted or curative therapies that aim to improve red cell pathophysiology, especially in the context of inherited hemoglobin disorders, such as sickle cell disease. SUMMARY: Red cell pathophysiology can be therapeutically targeted and the improvements in membrane and cellular biophysics and blood rheology can now be feasibly assessed via new microfluidic biomarker assays. Recent advances provide a new hope and novel treatment options for major red cell ailments, including inherited hemoglobin disorders, membrane disorders, and other pathologies of the red cell, such as malaria.
Subject(s)
Biomarkers , Biophysical Phenomena , Cell Physiological Phenomena , Disease Susceptibility , Erythrocytes/physiology , Disease Management , Hematologic Tests/methods , Hematologic Tests/standards , Hemoglobinopathies/blood , Hemoglobinopathies/diagnosis , Hemoglobinopathies/etiology , Hemoglobinopathies/therapy , Humans , Microfluidics/methods , RheologyABSTRACT
Curcuminoids, polyphenol compounds in turmeric, possess several pharmacological properties including antioxidant, iron-chelating, and anti-inflammatory activities. Effects of curcuminoids in thalassemia patients have been explored in a limited number of studies using different doses of curcuminoids. The present study aims to evaluate the effects of 24-week curcuminoids supplementation at the dosage of 500 and 1000 mg/day on iron overload, oxidative stress, hypercoagulability, and inflammation in non-transfused ß-thalassemia/Hb E patients. In general, both curcuminoids dosages significantly lowered the levels of oxidative stress, hypercoagulability, and inflammatory markers in the patients. In contrast, reductions in iron parameter levels were more remarkable in the 1000 mg/day group. Subgroup analysis revealed that a marker of hypercoagulability was significantly decreased only in patients with baseline ferritin ≤ 1000 ng/ml independently of curcuminoids dosage. Moreover, the alleviation of iron loading parameters was more remarkable in patients with baseline ferritin > 1000 ng/ml who receive 1000 mg/day curcuminoids. On the other hand, the responses of oxidative stress markers were higher with 500 mg/day curcuminoids regardless of baseline ferritin levels. Our study suggests that baseline ferritin levels should be considered in the supplementation of curcuminoids and the appropriate curcuminoids dosage might differ according to the required therapeutic effect. Thai Clinical Trials Registry (TCTR): TCTR20200731003; July 31, 2020 "retrospectively registered".
Subject(s)
Diarylheptanoids/therapeutic use , Dietary Supplements , Hemoglobin E/genetics , Hemoglobinopathies/drug therapy , Inflammation/drug therapy , Iron Overload/drug therapy , Thrombophilia/drug therapy , Adolescent , Adult , Biomarkers , Blood Proteins/analysis , Cytokines/blood , Diarylheptanoids/administration & dosage , Diarylheptanoids/pharmacology , Dose-Response Relationship, Drug , Female , Ferritins/blood , Hemoglobinopathies/blood , Hemoglobinopathies/complications , Hemoglobinopathies/genetics , Heterozygote , Humans , Inflammation/blood , Inflammation/etiology , Iron Overload/etiology , Male , Malondialdehyde/blood , Middle Aged , Oxidative Stress/drug effects , Reactive Oxygen Species/blood , Retrospective Studies , Thrombophilia/blood , Thrombophilia/etiology , Young Adult , beta-Globins/genetics , beta-Thalassemia/blood , beta-Thalassemia/complications , beta-Thalassemia/drug therapy , beta-Thalassemia/geneticsSubject(s)
Erythroblasts/ultrastructure , Erythrocytes/ultrastructure , Inclusion Bodies/chemistry , alpha-Globins/analysis , Child , Female , Fetal Hemoglobin/analysis , Hemoglobinopathies/blood , Hemoglobinopathies/genetics , Heterozygote , Humans , Splenectomy , Young Adult , beta-Thalassemia/blood , beta-Thalassemia/genetics , beta-Thalassemia/surgeryABSTRACT
ABSTRACT Objective: To describe two cases of unusual variants of sickle cell disease. Case description: We present two cases of sickle cell disease variants (haemoglobinopathies), from unrelated families, in the state of Balochistan (Pakistan). One was diagnosed with sickle cell disease in the haemoglobin electrophoresis, whereas the other was diagnosed with sickle cell SE disease. Both were diagnosed based on the presentation of osteomyelitis. Comments: Haemoglobin SD disease (Hb SD) and haemoglobin SE disease (Hb SE) are rare haemoglobinopathies in the world. The lack of available literature suggests that both are variants of sickle cell disease (SCD), with heterogeneous nature. The prevalence of sickle cell disease with compound heterozygotes was found at a variable frequency in the population of the Asian Southeast. The frequency of osteomyelitis in SCD is 12 to 18%, but its occurrence among variant haemoglobinopathies is little reported. Both reported cases presented with osteomyelitis as a characteristic of the disease presentation.
RESUMO Objetivo: Descrever dois casos de variantes raras da hemoglobinopatia falciforme. Descrição do caso: Apresentamos aqui dois casos de hemoglobinopatias variantes das células falciformes, de famílias não relacionadas, no estado do Baluchistão (Paquistão), sendo um diagnosticado como doença da hemoglobina SD na eletroforese de hemoglobina, enquanto o outro com doença da hemoglobina SE. Ambos foram diagnosticados a partir da apresentação de osteomielite. Comentários: Hemoglobina SD (Hb SD) e hemoglobina SE (Hb SE) são hemoglobinopatias raras no mundo. A escassez de literatura disponível sugere que ambas são variantes da doença falciforme (DF) com natureza heterogênea. A prevalência de hemoglobinopatia falciforme com heterozigosidade composta foi encontrada com frequência variável na população do sudeste asiático. A frequência de osteomielite na DF é de 12 a 18%, mas sua ocorrência entre as hemoglobinopatias falciformes variantes é pouco relatada. Os dois casos reportados apresentaram osteomielite como característica de apresentação da doença.
Subject(s)
Humans , Male , Female , Child , Osteomyelitis/diagnosis , Blood Protein Electrophoresis/methods , Hemoglobinopathies/genetics , Anemia, Sickle Cell/diagnosis , Anemia, Sickle Cell/genetics , Osteomyelitis/etiology , Osteomyelitis/drug therapy , Pakistan/ethnology , Magnetic Resonance Imaging/methods , Radiography/methods , Mass Screening/standards , Mass Screening/ethics , Prevalence , Administration, Oral , Treatment Outcome , Administration, Intravenous , Hemoglobinopathies/diagnosis , Hemoglobinopathies/blood , Heterozygote , Hydroxyurea/administration & dosage , Hydroxyurea/therapeutic use , Anemia, Sickle Cell/complications , Anemia, Sickle Cell/epidemiology , Anti-Bacterial Agents/administration & dosage , Anti-Bacterial Agents/therapeutic use , Antisickling Agents/administration & dosage , Antisickling Agents/therapeutic useABSTRACT
Despite estimated high prevalence of inherited hemoglobin (Hb) disorders among tribal populations in Madhya Pradesh State, India, the burden of disease is unknown, leading to high morbidity and associated mortality. Our aim was to screen tribal populations in designated tribal districts of Madhya Pradesh State for various hemoglobinopathies and to estimate the prevalence and plausible cause of anemia. The present study screened a total of 3992 tribal individuals comprised of students of Tribal schools, ashrams of Dindori, Mandla, and Chhindwara districts of Madhya Pradesh State. Screening of hemoglobinopathies was done using Hb electrophoresis and or high performance liquid chromatography (HPLC), α-thalassemia (α-thal) was detected using polymerase chain reaction (PCR). The median age of the studied cohort was 15 years (interquartile range 13-16 years). High prevalence (76.7%) of anemia was observed among the studied cohort. The prevalence of sickle cell trait and sickle cell disease varies from 10.7 to 15.6% and 0.4 to 0.8%, respectively. The allele frequency of sickle cell gene was highest in the Pradhan tribe followed by the Panika tribe. Dindori district had the highest prevalence of sickle cell trait. ß-Thalassemia (ß-thal) trait was observed in only 1.4% of the screened population. α Gene deletions were observed in 84.7% individuals. Significant association of α gene deletion mutations with mean Hb, mean corpuscular volume (MCV), and mean corpuscular Hb (MCH) was observed. The Bharia tribe showed the highest prevalence for α-thal. For comprehensive health care, effective intervention programs are needed to reduce the high prevalence of anemia and hemoglobinopathies among tribes.
Subject(s)
Anemia/epidemiology , Anemia/etiology , Ethnicity , Hemoglobinopathies/epidemiology , Hemoglobinopathies/etiology , Adolescent , Alleles , Cross-Sectional Studies , Erythrocyte Indices , Genotype , Hemoglobinopathies/blood , Hemoglobinopathies/diagnosis , Humans , India/epidemiology , Mutation , Odds Ratio , Population Surveillance , Prevalence , Young Adult , alpha-Globins/geneticsABSTRACT
High prevalence of hemoglobin (Hb) disorders mandates national programs for screening and genetic counseling in many countries. Increased Hb A2 levels are commonly associated with ß-thalassemias, however, various disorders including alteration of δ chains may result in decreased production of Hb A2, thus hindering the diagnosis of ß-thalassemias. The reported data reflect the experience of a large reference laboratory in the United States. In the current study, we have attempted to assess the prevalence and also tried to characterize the identified mutations in the HBD gene resulting in decreased Hb A2 levels. In our cohort, 1.6% of 6486 patients were found to have Hb A2 values of <1.9%. Bidirectional sequencing of the HBD gene demonstrated mutations in 20 cases (19.0% of the individuals with decreased Hb A2). In addition to the previously reported variants, one novel mutation (Hb A2-Utah or HBD: c.46T>C).
Subject(s)
Hemoglobin A2/metabolism , beta-Thalassemia/blood , beta-Thalassemia/genetics , delta-Globins/genetics , Adolescent , Adult , Aged , Aged, 80 and over , Alleles , Child , Child, Preschool , Erythrocyte Indices , Female , Genetic Association Studies , Genetic Predisposition to Disease , Genotype , Hemoglobin A2/genetics , Hemoglobinopathies/blood , Hemoglobinopathies/diagnosis , Hemoglobinopathies/epidemiology , Hemoglobinopathies/genetics , Humans , Infant , Male , Middle Aged , Mutation , United States/epidemiology , Young Adult , alpha-Globins , beta-Thalassemia/diagnosis , beta-Thalassemia/epidemiology , delta-Globins/metabolismABSTRACT
COVID-19 infection is less common in children (with higher fetal hemoglobin levels). In our preliminary study, we also observed a low prevalence and fatality of COVID-19 in countries with high rate of hemoglobinopathy carries. Given these two facts, the hemoglobin structure can play a role in the physiopathology of COVID-19 disease. Several drugs are known to increase fetal hemoglobin in adults. Adding these drugs to COVID-19 clinical trials may improve the patients' outcomes.