RESUMEN
BACKGROUND: Thalassemia, an inherited hemoglobin disorder, has become a global public health problem due to population migration. Evidence-based strategies for thalassemia prevention in migrants are lacking. We characterized barriers to thalassemia screening and the burden of thalassemia in migrant workers in Thailand. METHODS: Multilingual demographic and KAP surveys were completed by 197 Thai, 119 Myanmar, and 176 Cambodian adults residing in Thailand. Thalassemia awareness, socio-demographic predictors, and knowledge and attitude scores were compared between migrant and Thai subjects. Comprehensive thalassemia testing was performed for migrants. RESULTS: Migrants had extremely poor thalassemia awareness (4.1%) compared to Thai subjects (79.6%) and had lower thalassemia knowledge scores but similar attitude scores. Surveys identified differing sociodemographic factors predicting awareness in Thai and migrant subjects, as well as key misconceptions likely to hinder thalassemia screening uptake. Nearly all migrants consented to thalassemia testing. We identified abnormal hemoglobin profiles in 52.7% of migrants and a higher projected rate of severe thalassemia births in migrants. CONCLUSIONS: The high burden of thalassemia and tremendous knowledge gap in migrants needs urgent attention. Thalassemia screening was feasible and acceptable in our migrant population. Sociocultural and structural barriers merit further attention when designing thalassemia screening and prevention policies for migrants in Thailand and globally.
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Migrantes , Adulto , Pueblo Asiatico , Estudios Transversales , Estudios de Factibilidad , Humanos , Mianmar , TailandiaRESUMEN
BACKGROUND: Thalassemia is a common inherited hemoglobin disorder in Southeast Asia. Severe thalassemia can lead to significant morbidity for patients and economic strain for under-resourced health systems. Thailand's thalassemia prevention and control program has successfully utilized prenatal screening and diagnosis to reduce the incidence of severe thalassemia in Thai populations, but migrant populations are excluded despite having high thalassemia prevalence. We sought to identify key barriers to and facilitators of thalassemia screening and to develop tailored recommendations for providing migrants with access to thalassemia prevention and control. METHODS: We conducted 28 in-depth interviews and 4 focus group discussions (FGDs) in Chonburi, Thailand with Myanmar and Cambodian migrants, Thai healthcare providers, Thai parents of children affected by thalassemia, and migrant agents. RESULTS: Participant narratives revealed that migrants' lack of knowledge about the prevalence, manifestations, severity, and inherited nature of thalassemia led to misconceptions, fear, or indifference toward thalassemia and screening. Negative perceptions of pregnancy termination were based in religious beliefs but compounded by other sociocultural factors, presenting a key obstacle to migrant uptake of prenatal screening. Additionally, structural barriers included legal status, competing work demands, lack of health insurance, and language barriers. Participants recommended delivering public thalassemia education in migrants' native languages, implementing carrier screening, and offering thalassemia screening in convenient settings. CONCLUSIONS: An effective thalassemia prevention and control program should offer migrants targeted thalassemia education and outreach, universal coverage for thalassemia screening and prenatal care, and options for carrier screening, providing a comprehensive strategy for reducing the incidence of severe thalassemia in Thailand and establishing an inclusive model for regional thalassemia prevention and control.
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Migrantes , Niño , Accesibilidad a los Servicios de Salud , Humanos , Tamizaje Masivo , Tailandia , Cobertura Universal del Seguro de SaludRESUMEN
Event free survival at 24 months (EFS24) has been described as a powerful predictor for outcome in several subtypes of B cell lymphoma. However, it was limitedly described in T cell lymphoma. We explored the implication of EFS24 as a predictor marker for peripheral T cell lymphoma (PTCL). We reviewed 293 systemic PTCL patients at 13 nationwide major university hospitals in Thailand from 2007 to 2014. The median event free survival (EFS) and overall survival (OS) of PTCL patients in our cohort was 16.3 and 27.7 months with corresponding 2-year EFS and 2-year OS of 45.8% and 51.9%, respectively. A total of 118 patients achieved EFS24 (no events during the first 24 mo). Patients who achieved EFS24 had better OS than patients who did not (2-y OS 92% vs 18.8%; HR, 0.1; P < .001). The standardized mortality ratio of patients achieving EFS24 was 18.7 (95% CI, 14.6-22.8). Multivariable analysis demonstrated performance status, histologic subtype, remission status, and EFS24 achievement as independent predictors for OS. Our study affirmed the value of EFS24 as a powerful prognostic factor for PTCL. Further validation in prospective study setting is warranted.
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Linfoma de Células T Periférico/mortalidad , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Estimación de Kaplan-Meier , Linfoma de Células T Periférico/epidemiología , Linfoma de Células T Periférico/terapia , Masculino , Persona de Mediana Edad , Pronóstico , Supervivencia sin Progresión , Vigilancia en Salud Pública , Tailandia/epidemiología , Resultado del TratamientoRESUMEN
Recently, complications in patients with nontransfusion-dependent thalassemia (NTDT), in particular those with ß-thalassemia intermedia (ß-TI), were found to be significantly different from those in patients with transfusion dependent thalassemia (TDT), mainly ß-thalassemia major (ß-TM). However, this information is rather limited in other forms of NTDT. In this prospective study, adult Thai NTDT patients were interviewed and clinically evaluated for thalassemia related complications. Fifty-seven NTDT patients (age 18-74 years), 59.6% Hb E/ß-thalassemia and 40.4% Hb H disease, were recruited; 26.4% were splenectomized. The most common complications were gallstones (68.4%), osteoporosis (26.3%), and pulmonary hypertension (15.8%). Splenectomy was associated with higher rate of gallstones and serious infection (P = .001 and .052, respectively), consistent with a multivariate analysis (RR = 9.5, P = .044, and RR = 15.1, P = .043, respectively). In addition, a higher hemoglobin level was inversely associated with gallstones in both univariate and multivariate analyses (P = .01 and .022, respectively). Serum ferritin was associated with abnormal liver function (P = .002). In contrast to the previous study, the prevalence of thrombosis was less common in our population (1.7%), probably due to differences in transfusion therapy, ethnicity, and underlying genotypes. For the first time, this prospective study provided the current prevalence of NTDT related complications in a Southeast Asian population with a different underlying genetic basis compared with previous studies. Although individual prevalence of each complication might differ from other studies, several important clinical factors such as splenectomy, degree of anemia, and iron overload seem to be determining risks of developing these complications consistently across different ethnicities.
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Talasemia alfa/complicaciones , Talasemia beta/complicaciones , Adolescente , Adulto , Anciano , Pueblo Asiatico , Transfusión Sanguínea , Cálculos Biliares/etiología , Hemoglobina E , Hemoglobina H , Humanos , Hipertensión Pulmonar/etiología , Persona de Mediana Edad , Osteoporosis/etiología , Prevalencia , Estudios Prospectivos , Factores de Riesgo , Esplenectomía , Adulto JovenRESUMEN
Secondary central nervous system (CNS) relapse is a serious and fatal complication of diffuse large B cell lymphoma (DLBCL). Data on secondary CNS (SCNS) relapse were mostly obtained from western countries with limited data from developing countries. We analyzed the data of 2034 newly diagnosed DLBCL patients enrolled into the multi-center registry under Thai Lymphoma Study Group from setting. The incidence, September 2006 to December 2013 to represent outcome from a resource limited pattern, management, and outcome of SCNS relapse were described. The 2-year cumulative incidence (CI) of SCNS relapse was 2.7 %. A total of 729, 1024, and 281 patients were classified as low-, intermediate-, and high-risk CNS international prognostic index (CNS-IPI) with corresponding 2-year CI of SCNS relapse of 1.5, 3.1, and 4.6 %, respectively (p < 0.001). Univariate analysis demonstrated advance stage disease, poor performance status, elevated lactate dehydrogenase, presence of B symptoms, more than one extranodal organ involvement, high IPI, and high CNS-IPI group as predictive factors for SCNS relapse. Rituximab exposure and intrathecal chemoprophylaxis offered no protective effect against SCNS relapse. At the time of analysis, six patients were alive. Median OS in SCNS relapsed patients was significantly shorter than relapsed patients without CNS involvement (13.2 vs 22.6 months) (p < 0.001). Primary causes of death were progressive disease (n = 35, 63.6 %) and infection (n = 9, 16.7 %). In conclusion, although the incidence of SCNS relapse in our cohort was low, the prognosis was dismal. Prophylaxis for SCNS involvement was underused even in high-risk patients. Novel approaches for SCNS relapse prophylaxis and managements are warranted.
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Neoplasias del Sistema Nervioso Central/epidemiología , Recursos en Salud , Linfoma de Células B Grandes Difuso/epidemiología , Recurrencia Local de Neoplasia/epidemiología , Sistema de Registros , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Neoplasias del Sistema Nervioso Central/diagnóstico , Neoplasias del Sistema Nervioso Central/terapia , Femenino , Estudios de Seguimiento , Recursos en Salud/tendencias , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/terapia , Masculino , Persona de Mediana Edad , Recurrencia Local de Neoplasia/diagnóstico , Recurrencia Local de Neoplasia/terapia , Estudios Prospectivos , Tailandia/epidemiología , Adulto JovenRESUMEN
In this study, we report on 8 compound heterozygotes for mutations in the key erythroid transcription factor Krüppel-like factor 1 in patients who presented with severe, transfusion-dependent hemolytic anemia. In most cases, the red cells were hypochromic and microcytic, consistent with abnormalities in hemoglobin synthesis. In addition, in many cases, the red cells resembled those seen in patients with membrane defects or enzymopathies, known as chronic nonspherocytic hemolytic anemia (CNSHA). Analysis of RNA and protein in primary erythroid cells from these individuals provided evidence of abnormal globin synthesis, with persistent expression of fetal hemoglobin and, most remarkably, expression of large quantities of embryonic globins in postnatal life. The red cell membranes were abnormal, most notably expressing reduced amounts of CD44 and, consequently, manifesting the rare In(Lu) blood group. Finally, all tested patients showed abnormally low levels of the red cell enzyme pyruvate kinase, a known cause of CNSHA. These patients define a new type of severe, transfusion-dependent CNSHA caused by mutations in a trans-acting factor (Krüppel-like factor 1) and reveal an important pathway regulating embryonic globin gene expression in adult humans.
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Anemia Hemolítica/etiología , Hemoglobina Fetal/genética , Regulación de la Expresión Génica , Factores de Transcripción de Tipo Kruppel/genética , Mutación , Reacción a la Transfusión , Adolescente , Adulto , Secuencia de Aminoácidos , Anemia Hemolítica/sangre , Anemia Hemolítica/genética , Niño , Preescolar , Secuencia Conservada , Índices de Eritrocitos , Eritrocitos/metabolismo , Femenino , Hemoglobina Fetal/química , Orden Génico , Humanos , Lactante , Masculino , Datos de Secuencia Molecular , Unión Proteica , Dominios y Motivos de Interacción de Proteínas , Alineación de Secuencia , Adulto Joven , Globinas alfa/metabolismo , Globinas beta/metabolismoRESUMEN
Alpha thalassemia is the most common genetic disease in the world with the prevalence of carriers ranging from 5-50% in several populations. Coinheritance of two defective α-globin genes usually gives rise to a symptomatic condition, hemoglobin (Hb) H disease. Previously, it has been suggested from several studies in different populations that nondeletional Hb H disease (--/α(T)α or --/αα(T)) is generally more severe than the deletional type (--/-α). In this report, we describe four rare nondeletional α-thalassemia mutations in Thai individuals, including initiation codon mutation (HBA2:c.1delA), donor splice site mutation (IVSI-1, HBA1:c.95 + 1G>A), Hb Queens Park (HBA1:c.98T>A) [α32(B13)Met>Lys], and Hb Westmead (HBA2:c.369C>G) [α122(H5)His>Gln]. Interactions of the first three mutations with the α(0)-thalassemia resulted in nondeletional Hb H disease; however, their clinical presentations were rather mild and some were detected accidentally. This suggests that a genotype-phenotype correlation of α-thalassemia syndrome might be more heterogeneous and so the type of mutation does not simply imply the prediction of the resulting phenotype. Our data will be of use in future genetic counseling of such conditions that are increasingly identified thanks to the improvement of molecular analysis in routine laboratories.
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Codón Iniciador/genética , Hemoglobinopatías/genética , Hemoglobinas Anormales/genética , Mutación Missense , Sitios de Empalme de ARN/genética , Globinas alfa/genética , Adolescente , Adulto , Sustitución de Aminoácidos , Anemia/etiología , Niño , Preescolar , Dengue/sangre , Dengue/complicaciones , Femenino , Genotipo , Trastornos del Crecimiento/etiología , Hemoglobinopatías/sangre , Hemoglobinas Anormales/análisis , Humanos , Hallazgos Incidentales , Lactante , Masculino , Persona de Mediana Edad , Infecciones por Parvoviridae/sangre , Infecciones por Parvoviridae/complicaciones , Parvovirus B19 Humano , Linaje , Fenotipo , Esplenomegalia/etiología , Talasemia alfa/genéticaAsunto(s)
Anemia Hemolítica Congénita no Esferocítica/terapia , Trasplante de Células Madre Hematopoyéticas/métodos , Piruvato Quinasa/deficiencia , Errores Innatos del Metabolismo del Piruvato/terapia , Adolescente , Adulto , Anemia Hemolítica/etiología , Anemia Hemolítica Congénita no Esferocítica/complicaciones , Anemia Hemolítica Congénita no Esferocítica/epidemiología , Anemia Hemolítica Congénita no Esferocítica/mortalidad , Niño , Preescolar , Transfusión de Eritrocitos , Femenino , Estudios de Seguimiento , Enfermedad Injerto contra Huésped/etiología , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Trasplante de Células Madre Hematopoyéticas/mortalidad , Humanos , Masculino , Errores Innatos del Metabolismo del Piruvato/complicaciones , Errores Innatos del Metabolismo del Piruvato/epidemiología , Errores Innatos del Metabolismo del Piruvato/mortalidad , Estudios Retrospectivos , Análisis de Supervivencia , Adulto JovenRESUMEN
There are few stem cells in human peripheral blood (PB). Increasing the population and plasticity of stem cells in PB and applying it to regenerative medicine require suitable culture methods. In this study, leukocyte populations 250 mL of PB were collected using a blood separator before that were cultured in optimal cell culture medium for 4 to 7 days. After culturing, stemness characteristics were analyzed, and red blood cells were removed from the cultured cells. In our results, stemness markers of the leukocyte populations Sca-1+ CD45+, CD117+ CD45+, and very small embryonic-like stem cells CD34+ Lin- CD45- and CXCR4+ Lin- CD45- were significantly increased. Furthermore, the expression of stem cell genes OCT4 (POU5F1), NANOG, SOX2, and the self-renewal gene TERT was analyzed by quantitative real-time polymerase chain reaction in these cells, and it showed a significant increase. These cells could be candidates for multi-potential cells and were further induced using trans-differentiation culture methods. These cells showed multiple differentiation potentials for osteocytes, nerve cells, cardiomyocytes, and hepatocytes. These results indicate that appropriate culture methods can be applied to increase expression of pluripotent genes and plasticity. Leukocytes of human PB can be induced to trans-differentiate into pluripotent potential cells, which will be an important breakthrough in regenerative medicine.
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Células Madre Embrionarias , Telomerasa , Humanos , Células Madre Embrionarias/metabolismo , Diferenciación Celular , Genes Homeobox , Antígenos CD34/metabolismo , Células Cultivadas , Leucocitos/metabolismo , Telomerasa/genética , Proteína Homeótica Nanog/genética , Proteína Homeótica Nanog/metabolismo , Factores de Transcripción SOXB1/genéticaRESUMEN
Alpha thalassemia major (ATM) is a hemoglobinopathy that usually results in perinatal demise if in utero transfusions (IUTs) are not performed. We established an international registry (NCT04872179) to evaluate the impact of IUTs on survival to discharge (primary outcome) as well as perinatal and neurodevelopmental secondary outcomes. Forty-nine patients were diagnosed prenatally, 11 were diagnosed postnatally, and all 11 spontaneous survivor genotypes had preserved embryonic zeta-globin levels. We compared 3 groups of patients; group 1, prenatally diagnosed and alive at hospital discharge (n = 14), group 2, prenatally diagnosed and deceased perinatally (n = 5), and group 3, postnatally diagnosed and alive at hospital discharge (n = 11). Group 1 had better outcomes than groups 2 and 3 in terms of the resolution of hydrops, delivery closer to term, shorter hospitalizations, and more frequent average or greater neurodevelopmental outcomes. Earlier IUT initiation was correlated with higher neurodevelopmental (Vineland-3) scores (r = -0.72, P = .02). Preterm delivery after IUT was seen in 3/16 (19%) patients who continued their pregnancy. When we combined our data with those from 2 published series, patients who received ≥2 IUTs had better outcomes than those with 0 to 1 IUT, including resolution of hydrops, delivery at ≥34 weeks gestation, and 5-minute appearance, pulse, grimace, activity, and respiration scores ≥7. Neurodevelopmental assessments were normal in 17/18 of the ≥2 IUT vs 5/13 of the 0 to 1 IUT group (OR 2.74; P = .01). Thus, fetal transfusions enable the survival of patients with ATM and normal neurodevelopment, even in those patients presenting with hydrops. Nondirective prenatal counseling for expectant parents should include the option of IUTs.
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Talasemia alfa , Embarazo , Recién Nacido , Femenino , Humanos , Talasemia alfa/complicaciones , Talasemia alfa/terapia , Transfusión Sanguínea , Transfusión de Sangre Intrauterina/efectos adversos , Transfusión de Sangre Intrauterina/métodos , Edad Gestacional , Edema/etiologíaRESUMEN
Human genetic variation has enabled the identification of several key regulators of fetal-to-adult hemoglobin switching, including BCL11A, resulting in therapeutic advances. However, despite the progress made, limited further insights have been obtained to provide a fuller accounting of how genetic variation contributes to the global mechanisms of fetal hemoglobin (HbF) gene regulation. Here, we have conducted a multi-ancestry genome-wide association study of 28,279 individuals from several cohorts spanning 5 continents to define the architecture of human genetic variation impacting HbF. We have identified a total of 178 conditionally independent genome-wide significant or suggestive variants across 14 genomic windows. Importantly, these new data enable us to better define the mechanisms by which HbF switching occurs in vivo. We conduct targeted perturbations to define BACH2 as a new genetically-nominated regulator of hemoglobin switching. We define putative causal variants and underlying mechanisms at the well-studied BCL11A and HBS1L-MYB loci, illuminating the complex variant-driven regulation present at these loci. We additionally show how rare large-effect deletions in the HBB locus can interact with polygenic variation to influence HbF levels. Our study paves the way for the next generation of therapies to more effectively induce HbF in sickle cell disease and ß-thalassemia.
RESUMEN
Based on Thalassemia International Federation clinical practice guidelines (CPG) for non-transfusion dependent and transfusion dependent thalassemia, several measures should be routinely implemented such as monitoring and surveillance of thalassemia related complications for early detection and proper clinical management. To evaluate the prevalence and the performance of routine surveillance for thalassemia related complications during 2 periods; before and after published CPGs (2012-2014 vs 2015-2017), data from 524 adult thalassemia patients attended at Siriraj hospital were compared among different treating physician groups; thalassemia, private hematology, and internal medicine clinics. Three most common complications were osteopenia/osteoporosis (69.8%), gallstones (67.6%) and abnormal vitamin D level (67.6%). Iron overload has been widely evaluated (93.1%) followed by liver function test (82.3%). However, the rate of evaluation for other complications were significantly reduced and < 25% of patients were evaluated in several complications. Comparing among clinics, the surveillance rate has increased significantly for several endocrine complications only in patients treated at thalassemia clinic but not in others. This study was the first study that evaluated real-world practical management of thalassemia patient in terms of complication surveillance. This different clinical practice has called for an immediate policy change to improve and standardize a care for thalassemia patients in Thailand.
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Guías de Práctica Clínica como Asunto , Mejoramiento de la Calidad , Talasemia/terapia , Adulto , Necesidades y Demandas de Servicios de Salud , Humanos , Pautas de la Práctica en Medicina , TailandiaRESUMEN
INTRODUCTION: Peripheral T cell NHL (PTCL) and natural killer/T cell NHL (NKTCL) are relatively rare disorders. Data on clinical presentation, treatment and outcome are limited especially in older age groups. METHODS: We identified 127 patients with PTCL and NKTCL, excluding cutaneous T/NK cell lymphoma, aged over 60â¯years old from Thailand nationwide multicenter registry. RESULTS: Of 127 patients, median age of diagnosis was 67â¯years old. Patients aged older than 75â¯years old had similar characteristics to younger (60-74â¯years old) but higher comorbidity index. Seventy-nine patients (62.2%) received intensive/definite multi-agent chemotherapy, however, the proportion was significant lower in older patients (70.4% vs 34.5%, pâ¯<â¯.001). After a median follow up duration of 17.3â¯months, 2-year progression free survival and overall survival were 38.1% and 48.5%. Univariate and multivariable analysis demonstrated older age, poor performance status and absence of definite multi-agent chemotherapy were associated with inferior survival. Definite multi-agent lymphoma specific chemotherapy was an independent factor for overall survival after adjustment for age, comorbidity index, performance status and prognostic index for T cell lymphoma. CONCLUSION: Despite overall poor prognosis of PTCL and NKTCL in older adults, chemotherapy could result in objective response and long-term survival in selected patients of this vulnerable age group thus emphasizing the importance of comprehensive geriatric evaluation.
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Linfoma de Células T Periférico , Linfoma de Células T , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Humanos , Células Asesinas Naturales , Linfoma de Células T Periférico/tratamiento farmacológico , Linfoma de Células T Periférico/epidemiología , Pronóstico , Sistema de Registros , Estudios Retrospectivos , Linfocitos T , Tailandia/epidemiología , Resultado del TratamientoRESUMEN
Event-free survival at 12 months (EFS12) is a surrogate endpoint for long-term outcomes in many histologic lymphoma subtypes. However, most reports have primarily investigated the implication of EFS12 in advanced-stage non-Hodgkin lymphoma (NHL). There are limited data regarding the significance of EFS12 in early-stage NHL. Herein, we evaluated the prognostic significance of EFS12 in patients with stage 1 diffuse large B-cell lymphoma (DLBCL). Out of 282 patients with stage 1 DLBCL who received intensive therapy, 227 (80.5%) achieved EFS12. The 4-year overall survival (OS) was 91.4% and 4.0% for patients who achieved and failed to achieve EFS12, respectively. Multivariable analyses demonstrated response to treatment and achievement of EFS12 as independent predictors for OS. In conclusion, our study demonstrated EFS12 as a powerful prognostic factor for stage 1 DLBCL. Further validation in more extensive prospective studies is warranted.
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Protocolos de Quimioterapia Combinada Antineoplásica , Linfoma de Células B Grandes Difuso , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biomarcadores , Supervivencia sin Enfermedad , Humanos , Linfoma de Células B Grandes Difuso/diagnóstico , Linfoma de Células B Grandes Difuso/tratamiento farmacológico , Linfoma de Células B Grandes Difuso/epidemiología , Pronóstico , Supervivencia sin Progresión , Estudios Prospectivos , Sistema de Registros , TailandiaRESUMEN
Severe forms of α-thalassaemia, haemoglobin H disease and haemoglobin Bart's hydrops fetalis, are an important public health concern in Southeast Asia. Yet information on the prevalence, genetic diversity and health burden of α-thalassaemia in the region remains limited. We compiled a geodatabase of α-thalassaemia prevalence and genetic diversity surveys and, using geostatistical modelling methods, generated the first continuous maps of α-thalassaemia mutations in Thailand and sub-national estimates of the number of newborns with severe forms in 2020. We also summarised the current evidence-base for α-thalassaemia prevalence and diversity for the region. We estimate that 3595 (95% credible interval 1,717-6,199) newborns will be born with severe α-thalassaemia in Thailand in 2020, which is considerably higher than previous estimates. Accurate, fine-scale epidemiological data are necessary to guide sustainable national and regional health policies for α-thalassaemia management. Our maps and newborn estimates are an important first step towards this aim. Editorial note: This article has been through an editorial process in which the authors decide how to respond to the issues raised during peer review. The Reviewing Editor's assessment is that all the issues have been addressed (see decision letter).
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Costo de Enfermedad , Topografía Médica , Talasemia alfa/epidemiología , Variación Genética , Hemoglobinas/genética , Humanos , Mutación , Prevalencia , Tailandia/epidemiologíaRESUMEN
At present, thalassemia diseases are classified into transfusion-dependent thalassemia and non-transfusion-dependent thalassemia. This classification is based on the clinical severity of patients determining whether they do require regular blood transfusions to survive (transfusion-dependent thalassemia) or not (non-transfusion-dependent thalassemia). In addition to the previous terminology of "thalassemia major" or "thalassemia intermedia," this classification has embraced all other forms of thalassemia syndromes such as α-thalassemia, hemoglobin E/ß-thalassemia and combined α- and ß-thalassemias. Definitive diagnosis of thalassemia and hemoglobinopathies requires a comprehensive workup from complete blood count, hemoglobin analysis, and molecular studies to identify mutations of globin genes.
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Talasemia/diagnóstico , Transfusión Sanguínea , Estudios de Asociación Genética , Pruebas Genéticas , Hemoglobinas/genética , Hemoglobinas/metabolismo , Humanos , Tamizaje Masivo , Mutación , Fenotipo , Talasemia/sangre , Talasemia/genética , Talasemia/terapia , Talasemia alfa/sangre , Talasemia alfa/diagnóstico , Talasemia alfa/genética , Talasemia alfa/terapia , Talasemia beta/sangre , Talasemia beta/diagnóstico , Talasemia beta/genética , Talasemia beta/terapiaRESUMEN
OBJECTIVES: There are more than 200 known mutations found in patients with ß-thalassemia, a possibility to identify an unknown or novel mutation becomes less possible. Here, we report a novel mutation in a patient from Thailand who presented with chronic hemolytic anemia. METHODS: A comprehensive hematology and DNA analysis was applied in the index patient and her mother. RESULTS: Hematological and hemoglobin analyses were consistent with the clinical diagnosis of Hb E/ß0-thalassemia. However, we could find only Hb E heterozygous mutation using our common polymerase chain reaction-based mutation detection of the ß-globin genes. Furthermore, the molecular analysis demonstrated a novel T-deletion at codon 42 of the second exon of the ß-globin gene which we named 'Hb Yala' according to the origin of this index family. DISCUSSION: This mutation was assumed to generate a truncated ß-globin chain terminating at codon 60 with possible unstable variant leading to a 'null' or ß0-thalassemia. However, the clinical phenotype was surprisingly mild and no other ameliorating genetic factors, including co-inheritance of α-thalassemia and high propensity of Hb F by Xmn I polymorphism, were found. CONCLUSION: This report has provided evidence that genotype-phenotype correlation in thalassemia syndromes is highly complex and a correct clinical severity classification of thalassemia should be mainly based on clinical evaluation.
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Mutación del Sistema de Lectura , Hemoglobinas Anormales/genética , Talasemia beta/genética , Niño , Femenino , Humanos , TailandiaRESUMEN
Background and Objectives. To explore the role of cis-regulatory sequences within the ß globin gene cluster at chromosome 11 on human γ globin gene expression related to Hb E allele, we analyze baseline hematological data and Hb F values together with ß globin haplotypes in homozygous Hb E. Patients and Methods. 80 individuals with molecularly confirmed homozygous Hb E were analyzed for the ß globin haplotypes and Xmn I polymorphism using PCR-RFLPs. 74 individuals with complete laboratory data were further studied for association analyses. Results. Eight different ß globin haplotypes were found linked to Hb E alleles; three major haplotypes were (a) (III), (b) (V), and (c) (IV) accounting for 94% of Hb E chromosomes. A new haplotype (Th-1) was identified and most likely converted from the major ones. The majority of individuals had Hb F < 5%; only 10.8% of homozygous Hb E had high Hb F (average 10.5%, range 5.8-14.3%). No association was found on a specific haplotype or Xmn I in these individuals with high Hb F, measured by alkaline denaturation. Conclusion. The cis-regulation of γ globin gene expression might not be apparent under a milder condition with lesser globin imbalance such as homozygous Hb E.