RESUMO
Thalassemia is a heterogeneous group of inherited anemias having in common defective biosynthesis of one or more of the globin chain subunits of human hemoglobin. Their origins lie in inherited mutations that impair the expression of the affected globin genes. Their pathophysiology arises from the consequent insufficiency of hemoglobin production and the imbalance in the production of globin chains resulting in the accumulation of insoluble unpaired chains. These precipitate and damage or destroy developing erythroblasts and erythrocytes producing ineffective erythropoiesis and hemolytic anemia. Treatment of severe cases requires lifelong transfusion support with iron chelation therapy.
Assuntos
Talassemia , Talassemia beta , Humanos , Talassemia beta/genética , Medicina Molecular , Síndrome , Talassemia/genética , HemoglobinasRESUMO
Thalassaemia is a common hereditary haemolytic anaemia. Mild cases of this disease may be asymptomatic, while patients with severe thalassaemias require high-dose blood transfusions and regular iron removal to maintain life or haematopoietic stem cell transplantation to be cured, imposing an enormous familial and social burden. Therefore, early, timely, and accurate screening of patients is of great importance. In recent years, with the continuous development of thalassaemia screening technologies, the accuracy of thalassaemia screening has also improved significantly. This article reviews the current research on thalassaemia screening.
Assuntos
Talassemia , Talassemia beta , Transfusão de Sangue , Humanos , Programas de Rastreamento , Talassemia/diagnóstico , Talassemia/genéticaRESUMO
Thalassemias (α, ß, γ, δ, δß, and εγδß) are the most common genetic disorders worldwide and constitute a heterogeneous group of hereditary diseases characterized by the deficient synthesis of one or more hemoglobin (Hb) chain(s). This leads to the accumulation of unstable non-thalassemic Hb chains, which precipitate and cause intramedullary destruction of erythroid precursors and premature lysis of red blood cells (RBC) in the peripheral blood. Non-thalassemic Hbs display high oxygen affinity and no cooperativity. Thalassemias result from many different genetic and molecular defects leading to either severe or clinically silent hematologic phenotypes. Thalassemias α and ß are particularly diffused in the regions spanning from the Mediterranean basin through the Middle East, Indian subcontinent, Burma, Southeast Asia, Melanesia, and the Pacific Islands, whereas δß-thalassemia is prevalent in some Mediterranean regions including Italy, Greece, and Turkey. Although in the world thalassemia and malaria areas overlap apparently, the RBC protection against malaria parasites is openly debated. Here, we provide an overview of the historical, geographic, genetic, structural, and molecular pathophysiological aspects of thalassemias. Moreover, attention has been paid to molecular and epigenetic pathways regulating globin gene expression and globin switching. Challenges of conventional standard treatments, including RBC transfusions and iron chelation therapy, splenectomy and hematopoietic stem cell transplantation from normal donors are reported. Finally, the progress made by rapidly evolving fields of gene therapy and gene editing strategies, already in pre-clinical and clinical evaluation, and future challenges as novel curative treatments for thalassemia are discussed.
Assuntos
Talassemia , Hemoglobinas/genética , Humanos , Fenótipo , Talassemia/genéticaRESUMO
Transfusion combined with chelation therapy for severe ß thalassemia syndromes (transfusion-dependent thalassemia [TDT]) has been successful in extending life expectancy, decreasing comorbidities and improving quality of life. However, this puts lifelong demands not only on the patients but also on the health care systems that are tasked with delivering long-term treatment and comprehensive support. Prevention programs and curative approaches are therefore an important part of overall strategy. Curative treatments alter the dynamic of a patient's health care costs, from financial commitment over 50 years, into a potential "one-off" investment. Since the 1980s, this has usually been available only to the 30% or so of young children with matched sibling donors. By improving the safety of matched related donors and haploidentical hematopoietic stem cell transplants, the potential size of the donor pool for curative therapies may be increased. Recent advances in gene therapy demonstrate that even patients lacking a matched donor can be rendered transfusion independent with an autograft of genetically modified autologous stem cells, with a low short-term risk. Noncurative treatments are also of potential value by decreasing use of blood and chelators and decreasing hospital visits. An example is luspatercept, an activin-receptor trap that modifies transforming growth factor-ß signaling, thereby increasing the efficiency of erythropoiesis. This has entered phase 3 clinical trials for TDT and non-TDT and, usefully increases in both Hb and quality of life in non-TDT as well as decreasing transfusion requirements in TDT. Other novel noncurative treatments are entering clinical trials such improvement of erythropoiesis through pharmacological manipulation of hepcidin and iron metabolism.
Assuntos
Terapia Genética/métodos , Transplante de Células-Tronco/métodos , Talassemia/terapia , Doadores não Relacionados , Aloenxertos , Autoenxertos , Humanos , Talassemia/genética , Talassemia/metabolismoRESUMO
Global migration has resulted in a larger geographical spread of people with risk of hereditary anaemias. This leads to an increased incidence of pregnant women with rare diseases, including thalassaemia also in Scandinavia. Thalassaemia can cause severe anaemia and other complications during pregnancy, like risk of miscarriage, intrauterine fetal death, abruptio, intrauterine growth retardation, hypertension, gestational diabetes and pre-eclampsia. In this article, we focus on the aetiology, assessment, antenatal care and treatment of pregnant women with thalassaemia.
Assuntos
Complicações Hematológicas na Gravidez/prevenção & controle , Talassemia , Transfusão de Sangue , Terapia por Quelação , Feminino , Humanos , Sobrecarga de Ferro/prevenção & controle , Gravidez , Talassemia/diagnóstico , Talassemia/etiologia , Talassemia/genética , Talassemia/terapiaRESUMO
Thalassemia is the commonest monogenic disease and manifests as severe anemia. It is increasingly encountered outside the Mediterranean region, Africa, Middle East, and Southeast Asia because of immigration. Pregnancy, previously uncommon in patients with homozygous ß-thalassemia, is encountered increasingly because of improved management and assisted reproduction technology; however, preconceptional problems that include anemia, iron overload, cardiac dysfunction, thromboembolism, alloimmunization, infections, and endocrine and bone disorders, could influence maternal and obstetric outcome. Although, successful pregnancy in thalassemia trait carriers and women with hemoglobin H disease is more common, there is still increased risk of obstetric and perinatal complications. Prenatal diagnosis to exclude fetal homozygous thalassemia and other congenital anomalies, together with close monitoring of the pregnancy, would optimize outcome. Further research is warranted to elucidate the fetal safety of iron chelation therapy and potential effect of pregnancy on long-term maternal health outcome, especially following occurrence of maternal complications.
Assuntos
Complicações Hematológicas na Gravidez/terapia , Cuidado Pré-Natal/métodos , Talassemia/complicações , Talassemia/terapia , Anemia/etiologia , Anemia/terapia , Feminino , Heterozigoto , Humanos , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/terapia , Gravidez , Complicações Hematológicas na Gravidez/genética , Resultado da Gravidez , Diagnóstico Pré-Natal , Técnicas de Reprodução Assistida , Talassemia/genéticaRESUMO
OBJECTIVE: to explore parents' personal attitudes towards non-invasive prenatal diagnosis in the context of their own experiences caring for a child affected with a genetic condition or after the loss of a fetus, infant, or child due to the condition. METHODS: we collected in-depth data from parents via either focus groups or individual interviews. DESIGN: this was a cross-sectional interpretive study based on grounded theory. SETTING: United Kingdom. PARTICIPANTS: 17 parents (13 women and four men) who were carriers of a serious autosomal recessive condition: spinal muscular atrophy, cystic fibrosis or thalassaemia. All had a child (living or deceased) with the condition. FINDINGS: parents experienced changes in reproductive self-identity due to their experiences of having an affected child: this influenced their views of non-invasive prenatal testing. They began their reproductive journeys 'naively', but described feelings of reproductive vulnerability after the diagnosis of the child and consequent realisation of risks to future children. They viewed non-invasive prenatal testing as a way to reduce threats to unborn children, while allowing prenatal diagnosis. KEY CONCLUSIONS: when parents lose a child they may use emotional guarding, delayed pregnancy disclosure and avoidance of harmful activities to cope in future pregnancies. Parents who want to consider early prenatal testing are less able to utilise these strategies, but non-invasive methods allow them to reduce the risk. IMPLICATIONS FOR PRACTICE: midwives should be sensitive to parents' reproductive vulnerability after genetic diagnosis of a child and ensure they are supported to consider the option of non-invasive prenatal testing if appropriate.
Assuntos
Aceitação pelo Paciente de Cuidados de Saúde , Diagnóstico Pré-Natal , Natimorto/psicologia , Adulto , Estudos Transversais , Fibrose Cística/diagnóstico , Fibrose Cística/genética , Feminino , Grupos Focais , Humanos , Recém-Nascido , Entrevistas como Assunto , Masculino , Pessoa de Meia-Idade , Tocologia , Atrofia Muscular Espinal/diagnóstico , Atrofia Muscular Espinal/genética , Gravidez , Talassemia/diagnóstico , Talassemia/genéticaRESUMO
Hb Quong Sze [Hb QS, HBA2: c.377T > C (or HBA1)] is a common nondeletional thalassemia in southern China. It is one of the major alleles causing nondeletional Hb H (ß4) disease in the Chinese population. There is no strategy currently in place that aims to screen using hematological index cutoffs for this variant. This study was carried out to evaluate whether it is effective to use mean corpuscular hemoglobin (MCH) <27.0 pg as a screening test in the first step of screening for Hb QS carriers in southern China. The data of hematological testing in the Hb QS carriers obtained from couples who underwent prenatal thalassemia screening, regardless of the red blood cell (RBC) indices, were retrospectively reviewed. A total of 51 Hb QS carriers were identified, giving a prevalence rate of 0.2%; among these, 45 were Hb QS heterozygotes. The values of hemoglobin (Hb), MCV and mean corpuscular Hb (MCH) in the 45 Hb QS heterozygotes were 13.2 ± 1.8 g/dL, 75.2 ± 3.3 fL and 24.5 ± 0.5 pg, respectively. Eight heterozygotes (17.8%) had an MCV value of >80.0 fL, ranging from 80.9 to 84.1 fL, and would not be detected using the cutoff value of MCV <80.0 fL as a criterion for thalassemia screening. However, if screening had been based on the MCH <27.0 pg value, all 45 Hb QS heterozygotes would have been detected. Using a cutoff value of MCH <27.0 pg in nondeletional thalassemia screening would greatly decrease the DNA diagnosis burden.
Assuntos
Hemoglobinas Glicadas/genética , Hemoglobinas Anormais/genética , Heterozigoto , Diagnóstico Pré-Natal , Talassemia/genética , Adulto , China/epidemiologia , Humanos , Masculino , Programas de Rastreamento , Programas Nacionais de Saúde , Estudos Retrospectivos , Talassemia/epidemiologiaRESUMO
Erythrocytes from sickle cell anaemia (SCA) patients continuously produce larger amounts of pro-oxidants than normal cells. Oxidative stress seems to primarily affect the membrane and results in haemolysis. The use of antioxidants in vitro reduces the generation of pro-oxidants. To evaluate the impact of vitamins C (VitC) and E (VitE) supplementation in SCA patients, patients over 18 years were randomly assigned to receive VitC 1400 mg + VitE 800 mg per day or placebo orally for 180 d. Eighty-three patients were enrolled (44 vitamins, 39 placebo), median age 27 (18-68) years, 64% female. There were no significant differences between the two groups regarding clinical complications or baseline laboratorial tests. Sixty percent of the patients were VitC deficient, 70% were VitE deficient. Supplementation significantly increased serum VitC and E. However, no significant changes in haemoglobin levels were observed, and, unexpectedly, there was a significant increase in haemolytic markers with vitamin supplementation. In conclusion, VitC + VitE supplementation did not improve anaemia and, surprisingly, increased markers of haemolysis in patients with SCA and S-ß(0) -thalassaemia. The exact mechanisms to explain this findings and their clinical significance remain to be determined.
Assuntos
Anemia Falciforme/sangue , Antioxidantes/efeitos adversos , Ácido Ascórbico/efeitos adversos , Suplementos Nutricionais/efeitos adversos , Hemólise/efeitos dos fármacos , Vitamina E/efeitos adversos , Adolescente , Adulto , Idoso , Anemia Falciforme/tratamento farmacológico , Antioxidantes/administração & dosagem , Antioxidantes/uso terapêutico , Ácido Ascórbico/administração & dosagem , Ácido Ascórbico/uso terapêutico , Biomarcadores , Método Duplo-Cego , Uso de Medicamentos/estatística & dados numéricos , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Qualidade de Vida , Espécies Reativas de Oxigênio , Traço Falciforme/sangue , Traço Falciforme/tratamento farmacológico , Traço Falciforme/genética , Talassemia/sangue , Talassemia/tratamento farmacológico , Talassemia/genética , Vitamina E/administração & dosagem , Vitamina E/uso terapêutico , Adulto JovemRESUMO
OBJECTIVE: To evaluate the effectiveness of offering antenatal screening for sickle cell disease and thalassaemia in primary care as a way of facilitating earlier uptake of screening. DESIGN: Partial factorial cluster randomised controlled trial. SETTING: 25 UK general practices from deprived inner city areas. PARTICIPANTS: Anonymised data on all pregnant women attending participating practices during a six month period before randomisation and a seven month period after randomisation. This included 1708 eligible women. INTERVENTION: Practices were randomised to three groups for seven months: parallel testing in general practice (tests for sickle cell disease and thalassaemia offered to both parents when pregnancy was first reported); sequential testing in general practice (tests offered to mothers when pregnancy was first reported, and subsequently to the partners of women who were found to be carriers); and midwife care (tests offered to mothers at first consultation with a midwife). MAIN OUTCOME MEASURES: The primary outcome (available for all women) was the proportion of eligible women screened before 10 weeks' (70 days') gestation. Secondary outcomes were an offer of screening to women before 10 weeks' gestation, gestational age at testing, mean interval from first visit to the general practice visit to screening, and women's knowledge of the carrier status of their baby's father before 77 days' (11 weeks') gestation. The study was designed to detect a 20% absolute increase in screening uptake. Cluster level analyses were adjusted for age group, parity, ethnic group, primary care organisation, and number of general practitioners per practice. RESULTS: Data were analysed for 1708 eligible women. In the midwife care arm, 2% (9/441) of women were screened before 10 weeks' gestation compared with 24% (161/677) in the GP parallel testing arm and 28% (167/590) in the GP sequential testing arm. The estimated adjusted difference between the midwife care and GP parallel testing arms was 16.5% (95% confidence interval 7.1% to 25.8%; P=0.002) and between the midwife care and GP sequential testing arms was 27.8% (14.8% to 40.7%; P<0.001). By 26 weeks' gestation the proportion of women screened across the three trial arms was similar (81%). The proportion of women who knew the carrier status of the baby's father by 11 weeks' gestation was 0% (0/441) in the midwife care arm, 2% (13/677) in the GP parallel testing arm (P=0.003), and 1% (3/590) in the GP sequential testing arm (P=0.374). CONCLUSION: Offering antenatal screening for sickle cell disease and thalassaemia as part of consultations for pregnancy confirmation in primary care increases the proportion of women screened before 10 weeks' gestation. Even with intervention, however, only a minority of women were screened before 10 weeks. Additional interventions should be considered to achieve testing early in pregnancy for most women wanting such tests so that couples with affected pregnancies have less time pressure to choose options, which may include termination of the pregnancy. TRIAL REGISTRATION: Current Controlled Trials ISRCTN00677850.
Assuntos
Anemia Falciforme/diagnóstico , Triagem de Portadores Genéticos/métodos , Complicações Hematológicas na Gravidez/diagnóstico , Diagnóstico Pré-Natal/métodos , Talassemia/diagnóstico , Adulto , Anemia Falciforme/genética , Análise por Conglomerados , Diagnóstico Precoce , Medicina de Família e Comunidade , Feminino , Humanos , Masculino , Tocologia , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Diagnóstico Pré-Natal/estatística & dados numéricos , Talassemia/genética , Adulto JovemRESUMO
BACKGROUND: Several microdevices have been developed to perform only a single step of a genotyping process, such as PCR or detection by probe hybridization. Here, we describe a Lab-on-Chip (LoC) platform integrating a PCR amplification microreactor with a customable microarray for the detection of sequence variations on human genomic DNA. METHODS: Preliminary work was focused on developing the single analytical steps including PCR and labeling strategies of the amplified product by conventional reference systems. The optimized protocols included a 1:4 forward:reverse primer ratio for asymmetric PCR, and Cy5-dCTP multiple incorporation for the generation of a labeled PCR product to be hybridized to complementary probes bound to the chip surface. RESULTS: Final conditions were applied to the fully integrated LoC platform for the detection of the IVSI-110 G > A mutation in the human beta-globin (HBB) gene associated with beta-thalassemia, used as a model of genetic application, allowing for correct genotyping of 25 samples that were heterozygous, homozygous or wild-type for this mutation. CONCLUSIONS: The overall results show that the present platform is very promising for rapid identification of DNA sequence variations in an integrated, cost effective and convenient silicon chip format.
Assuntos
Dispositivos Lab-On-A-Chip , Técnicas de Diagnóstico Molecular/instrumentação , Reação em Cadeia da Polimerase , Carbocianinas/química , Carbocianinas/metabolismo , Nucleotídeos de Desoxicitosina/química , Nucleotídeos de Desoxicitosina/metabolismo , Variação Genética , Genoma Humano , Genótipo , Humanos , Técnicas de Diagnóstico Molecular/métodos , Análise de Sequência com Séries de Oligonucleotídeos , Talassemia/genética , Globinas beta/genéticaRESUMO
The hemoglobinopathies encompass a heterogeneous group of disorders associated with mutations in both the alpha-globin and beta-globin genes. Non-sickling disorders are found primarily in individuals of Mediterranean, Asian and Southeast Asian ancestry. With rapid growth in the Asian and Hispanic segments of the US population, the geographic distribution of hemoglobinopathies is expected to become significantly different from what it is today. The epidemiologic changes in the prevalence of non-sickling hemoglobin disorders have important implications for future public health programs, including newborn screening. The purpose of newborn screening for hemoglobinopathies is to identify clinically significant disorders and provide early education and specialized care prior to the onset of clinical symptoms. Although newborn screening for sickle cell disease is mandated in all states, screening for non-sickling hemoglobinopathies is directed in only one state and limited to reporting of a presumptive diagnosis in most other states. Early delivery of comprehensive care, as well as new and potentially curative therapies, has significantly improved the prognosis for affected patients. This review will consider the increasing prevalence of once uncommon hemoglobinopathies in the US, highlighting the rationale for expanding newborn screening beyond sickle cell disorders.
Assuntos
Hemoglobinopatias/diagnóstico , Triagem Neonatal , Asiático/genética , Asiático/estatística & dados numéricos , Povo Asiático/etnologia , California/epidemiologia , Cromatografia Líquida de Alta Pressão , Emigrantes e Imigrantes/estatística & dados numéricos , Sangue Fetal/química , Previsões , Hemoglobinopatias/sangue , Hemoglobinopatias/epidemiologia , Hemoglobinopatias/genética , Hemoglobinas Anormais/análise , Hemoglobinas Anormais/genética , Humanos , Recém-Nascido , Técnicas de Diagnóstico Molecular , Triagem Neonatal/métodos , Espectrometria de Massas em Tandem , Talassemia/etnologia , Talassemia/genética , Estados Unidos/epidemiologiaRESUMO
BACKGROUND: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons. OBJECTIVE: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for beta-thalassemia, alpha-thalassemia 1, or hemoglobin E (HbE) differed from that in control subjects and compound HbE/beta-thalassemia heterozygotes. DESIGN: In Thai women (n = 103), red blood cell indexes, iron status, non-transferrin-bound iron, and growth differentiation factor 15 were measured, and body iron was calculated. Fractional iron absorption was measured from meals fortified with isotopically labeled ((57)Fe) Fe sulfate, and iron utilization was measured by the infusion of ((58)Fe) Fe citrate. RESULTS: Iron utilization was approximately 15% lower in alpha-thalassemia 1 or beta-thalassemia heterozygotes than in controls. When corrected for differences in serum ferritin, absorption was significantly higher in the alpha- and beta-thalassemia groups, but not the HbE heterozygotes, than in controls. HbE/beta-thalassemia compound heterozygotes had lower iron utilization and higher iron absorption and body iron than did controls. Nontransferrin-bound iron and growth differentiation factor 15 were higher in the compound heterozygotes, but not in the other groups, than in the controls. CONCLUSIONS: In alpha-thalassemia 1 and beta-thalassemia heterozygotes with ineffective erythropoesis, dietary iron absorption is not adequately down-regulated, despite a modest increase in body iron stores. In populations with a high prevalence of these traits, a program of iron fortification could include monitoring for possible iron excess and for iron deficiency.
Assuntos
Eritrócitos/metabolismo , Alimentos Fortificados , Ferro da Dieta/farmacocinética , Ferro/metabolismo , Talassemia/metabolismo , Adolescente , Adulto , Disponibilidade Biológica , Feminino , Genótipo , Hemoglobina E/genética , Hemoglobina E/metabolismo , Heterozigoto , Humanos , Absorção Intestinal , Deficiências de Ferro , Isótopos de Ferro , Pessoa de Meia-Idade , Estado Nutricional , Talassemia/complicações , Talassemia/genética , Talassemia alfa/complicações , Talassemia alfa/genética , Talassemia alfa/metabolismo , Talassemia beta/complicações , Talassemia beta/genética , Talassemia beta/metabolismoRESUMO
PURPOSE: To determine the prevalence and geographic distribution of thalassemia and to evaluate the success of the thalassemia prevention and treatment programs in Iran. METHODS: Data were obtained from the National Thalassemia Registry of Iran, Iranian Blood Transfusion Organization, genetic laboratories involved in prenatal diagnosis, related pharmaceutical companies, and centers performing bone marrow transplantation for thalassemic patients. RESULTS: A total of 13,879 living patients have been registered, mostly from the northern and southern parts of Iran with the median age of 15 years. Twenty-three percent of patients were older than 20 years. The number of newly diagnosed cases has been decreased considerably after the start of the prevention program. Since the introduction of prenatal diagnosis, 2819 couples (2549 fetuses) have been tested, with only 6 false results. Elective abortion was not performed in 10 affected fetuses. Most common mutations detected were IVS II-1 and IVS I-5. In 2003, approximately 25% of the national blood products and 6 million vials of desferal were used for thalassemic patients. Overall, 340 patients have received allogeneic bone marrow transplantation, of those 46 patients deceased. Bloodborne infections have also been decreased significantly owing to the national screening of blood products for bloodborne viral infections. DISCUSSION: Owing to the national prevention program and provided special care, the age distribution of thalassemic patients in Iran is getting adapted to a full prevention and treatment program and life expectancy of these patients has been increased considerably. This shift in the age distribution of thalassemia, a traditionally considered pediatric disease, will face us with new challenges and the health care system should be prepared for this new face of thalassemia.
Assuntos
Talassemia/epidemiologia , Talassemia/prevenção & controle , Talassemia/terapia , Aborto Induzido , Adolescente , Adulto , Transplante de Medula Óssea , Feminino , Humanos , Irã (Geográfico) , Masculino , Programas Nacionais de Saúde , Gravidez , Diagnóstico Pré-Natal , Prevalência , Sistema de Registros , Talassemia/diagnóstico , Talassemia/genética , Transplante HomólogoRESUMO
Due to its excessive cost thalassemia management is a major health care problem in Sri Lanka. The majority of doctors are using only desferrioxamine (DFO), in grossly inadequate doses mainly because of its unavailability. Deferiprone (L1), which is more affordable, is not used due to fear of toxicity, as previously reported. Arthropathy attributed to L1 has been observed in some patients, and has led to the discontinuation of the drug in all patients, without scientific rationale. The proposed thalassemia prevention project for Uva Province is based on prevention of marriages between carriers. This could be achieved by carrier screening and counseling of teenagers and adolescents well before they select their partners. In Sri Lanka, people find their marriage partners at their work place or universities, by themselves, or with the help of professional marriage brokers (they are called Kapuwa), through relatives and close friends. This process of finding a partner may also be helped by paper advertisements. However, in addition to the appearance and attitude of the prospective partner, the caste, social background and horoscope are major considerations in selecting a partner. Even when they select partners on their own at the work place or university, they keep these factors in the back of their minds to ensure social acceptance. Many relationships are given up due to objections and advice from parents when the caste or social background does not match. A horoscope is a written document that almost every child gets, written by a professional horoscope reader and depending on the time of birth. It is believed, according to the horoscope, that a person's attitudes, desires, future prospects of finding a suitable partner, could be predicted. It is rare to proceed with a marriage if the horoscope does not match. These customs are considered less seriously among educated people when they find their partner at the work place or university. The concept of thalassemia risk-free marriages advocates promotion of marriages where at least one partner is a non-carrier. Success of such a project could be monitored at the time of marriage. This opinion survey indicates that the public is motivated to promote carrier screening and the prevention of thalassemia.
Assuntos
Quelantes de Ferro/uso terapêutico , Opinião Pública , Talassemia/epidemiologia , Aborto Eugênico/legislação & jurisprudência , Adolescente , Adulto , Transfusão de Sangue/estatística & dados numéricos , Terapia por Quelação/efeitos adversos , Terapia por Quelação/psicologia , Terapia Combinada , Coleta de Dados , Deferiprona , Desferroxamina/efeitos adversos , Desferroxamina/uso terapêutico , Uso de Medicamentos/estatística & dados numéricos , Feminino , Triagem de Portadores Genéticos , Aconselhamento Genético/estatística & dados numéricos , Testes Genéticos/legislação & jurisprudência , Testes Genéticos/psicologia , Humanos , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/efeitos adversos , Sobrecarga de Ferro/tratamento farmacológico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/prevenção & controle , Artropatias/induzido quimicamente , Masculino , Casamento , Programas Nacionais de Saúde , Piridonas/efeitos adversos , Piridonas/uso terapêutico , Sri Lanka/epidemiologia , Talassemia/genética , Talassemia/prevenção & controle , Talassemia/psicologia , Talassemia/terapia , Reação TransfusionalRESUMO
UNLABELLED: Concepts allied to ethnicity are increasingly coming under question as legitimate variables for use in health research. A randomised controlled trial of two ethnicity screening questions for ascertaining risk of carrying genes associated with sickle cell and thalassaemia illustrates the challenges and limitations of assessing an association of social constructs and genetic statuses. OBJECTIVES: To evaluate two candidate ethnicity screening questions in antenatal screening programmes in low, mixed and high sickle cell prevalence areas, and to identify time taken in administration of the questions by use of the following measures: (1) Proportions of respondents with missing ethnicity data and/or significant changes in ethnic/family origins upon re-interview. (2) Numbers of carriers of clinically significant haemoglobin disorders missed by ethnicity screening questions. (3) Time taken to explain screening question for sickle cell disease (SCD)/thalassaemia and obtain ethnic/family origins. (4) Proportion of clients providing usable ethnic/family origins data. (5) Reported ethnic/family origins in pregnant women at first booking with midwife. DESIGN: Ten-month (September 2002-June 2003) questionnaire study with random allocation to two self-administered ethnicity questions, comparison with laboratory results and results from re-interview. The settings were antenatal booking clinics in four geographical areas of England of varying expected foetal prevalence of SCD: very high (29.75 per 10,000 pregnancies); high (8.2); mixed high and low (1.29); and low (0.18). The subjects were 4,559 pregnant women at first booking with midwife. RESULTS: Proportions of respondents with missing ethnicity data and/or significant changes in ethnic/family origins upon re-interview were 4.33% (CI 2.63-6.68%) for a category-based question and 9.45% (CI 6.86-12.61%) for a binary plus open-ended question. Proportions of carriers missed were 5.74% (CI 2.34-11.46%) and 9.71% (CI 4.75-17.13%) by category-based and binary plus open-ended questions, respectively. Average time taken to ascertain ethnic/family origins for screening was between 2.17 and 5.12 minutes in different areas, and up to 15 minutes at the 95th centile. Usable ethnicity screening data was missing in 2.94% of instances. Errors in interpretation or missing data were 3.2% for a category-based question and 4.71% for a binary plus open-ended ethnicity question. Ethnicity Question A produces fewer cases of missing or misinterpreted data (p < 0.001). CONCLUSIONS: A category-based ethnicity screening question was more effective than a binary plus open-ended question. Using the more effective question, 5.74% (CI 2.34-11.46%) of significant haemoglobinopathies will be missed in a selective screening programme, and 4.33% (CI 2.63-6.68%) of replies to an ethnicity screening question will be unreliable when compared to information given upon re-interview. In specific carefully circumscribed situations, namely, in antenatal screening for sickle cell and thalassaemia, it is possible to measure the degree of association between social constructs of ethnicity and health status in a manner that may help in effecting policy decisions.
Assuntos
Família/etnologia , Predisposição Genética para Doença/etnologia , Testes Genéticos , Diagnóstico Pré-Natal , Traço Falciforme/etnologia , Inquéritos e Questionários/normas , Talassemia/etnologia , Adulto , Inglaterra , Feminino , Humanos , Recém-Nascido , Entrevistas como Assunto , Tocologia , Linhagem , Gravidez , Traço Falciforme/diagnóstico , Traço Falciforme/genética , Talassemia/diagnóstico , Talassemia/genéticaRESUMO
This overview describes the history of transfusion therapy and consequent iron overload in thalassemia. It emphasizes the importance of measurement of hepatic iron and reviews the history of chelation therapy. It briefly describes the discoveries of the genetic basis of thalassemia and the application of that knowledge in prenatal diagnosis. The review goes on to emphasize pharmaceutical efforts to induce fetal hemoglobin synthesis in thalassemic red cells and ends with a discussion of oral iron chelators, stem cell transplant, and the status of gene therapy.
Assuntos
Talassemia/história , Administração Oral , Adulto , Idoso , Animais , Boston , Administração de Caso/tendências , Terapia por Quelação , Criança , Pré-Escolar , Europa (Continente) , Feminino , Doenças Fetais/diagnóstico , Hemoglobina Fetal/biossíntese , Hemoglobina Fetal/genética , Terapia Genética , Insuficiência Cardíaca/etiologia , Insuficiência Cardíaca/prevenção & controle , Transplante de Células-Tronco Hematopoéticas , História do Século XX , História do Século XXI , Humanos , Lactente , Recém-Nascido , Bombas de Infusão Implantáveis , Quelantes de Ferro/administração & dosagem , Quelantes de Ferro/farmacocinética , Quelantes de Ferro/uso terapêutico , Sobrecarga de Ferro/etiologia , Sobrecarga de Ferro/prevenção & controle , Macaca fascicularis , Masculino , Camundongos , Pessoa de Meia-Idade , Gravidez , Complicações Hematológicas na Gravidez , Diagnóstico Pré-Natal/ética , Talassemia/diagnóstico , Talassemia/tratamento farmacológico , Talassemia/genética , Talassemia/prevenção & controle , Talassemia/terapia , Reação TransfusionalRESUMO
The first studies of the pharmacological induction of fetal hemoglobin were conducted in patients with sickle cell disease and thalassemia. Although hydroxyurea was approved by the FDA for the treatment of sickle cell disease in 1996, no similar pharmacological agent(s) has been approved for the treatment of patients with thalassemic disorders. The small-scale studies of the induction of fetal hemoglobin in thalassemia have been generally disappointing. The aim of this report is to provide a critical analysis of the factors that may be responsible for our failure to develop an effective fetal hemoglobin induction therapy for patients with thalassemia. We also describe several areas for future investigation that may be critically important for the development of an effective therapy for thalassemia.
Assuntos
Azacitidina/uso terapêutico , Hemoglobina Fetal/biossíntese , Expressão Gênica/efeitos dos fármacos , Globinas/biossíntese , Hidroxiureia/uso terapêutico , Talassemia/tratamento farmacológico , Anemia Falciforme/sangue , Anemia Falciforme/tratamento farmacológico , Anemia Falciforme/genética , Animais , Azacitidina/efeitos adversos , Azacitidina/farmacologia , Terapia Combinada , Aprovação de Drogas , Avaliação de Medicamentos , Avaliação Pré-Clínica de Medicamentos , Eritropoese/efeitos dos fármacos , Hemoglobina Fetal/genética , Regulação da Expressão Gênica , Globinas/genética , Humanos , Hidroxiureia/efeitos adversos , Hidroxiureia/farmacologia , Ferro/metabolismo , Células K562/efeitos dos fármacos , Células K562/metabolismo , Modelos Animais , Papio , Talassemia/sangue , Talassemia/genética , Talassemia/terapia , Reação Transfusional , Estados Unidos , United States Food and Drug AdministrationRESUMO
OBJECTIVE: Changing patterns of immigration to North America, along with improved treatment, have altered the clinical spectrum of thalassemia, one of the world's most common genetic diseases. The new demography of the disease, with its widely variable phenotypes, has implications for its diagnosis, counseling, and management. Characterization of the new spectrum of this ancient disease, now predominated by minority groups, is essential for optimizing survival. METHODS: The National Institutes of Health-sponsored North American Thalassemia Clinical Research Network (TCRN) conducted a cross-sectional study of 721 patients with thalassemia syndromes. A detailed chart review was undertaken to define the relationships between ethnic origins, genotype, and phenotype. These results were compared with 3 previous surveys of similar regions. To determine if the TCRN patient epidemiology is representative of North American patients, 87 additional programs were reviewed, and hemoglobinopathy programs from the 2 largest thalassemia regions, Ontario and California, were analyzed. RESULTS: A total of 721 patients completed analysis in the TCRN study, including 389 (54%) patients with beta-thalassemia major, 105 (15%) patients with beta-thalassemia intermedia, 95 (13%) patients with hemoglobin E-beta-thalassemia, and 132 (18%) patients with alpha-thalassemia. beta-Thalassemia predominated in Eastern North America. Hemoglobin E-beta-thalassemia and alpha-thalassemia were common on the Western continent. Genotype broadly correlated with the clinical phenotype. However, there was marked heterogeneity in clinical phenotype among patients with similar globin mutations. In beta-thalassemia disorders, coinheritance of the alpha-thalassemia trait, triplication of alpha-thalassemia genes, and heterozygosity for the dominant beta-thalassemia allele affected the clinical phenotype. In alpha-thalassemia disorders, structural mutations such as hemoglobin H-Constant Spring resulted in a severe hemoglobin H phenotype. Sixty percent of patients received regular transfusions, and 86% received regular iron-chelation therapy. Increased survival and decreasing birth rates of Mediterranean patients resulted in an aging Greek/Italian population being replaced by a young Asian/Middle Eastern population. Now, Asian patients account for >50% of the thalassemia population. Evidence of increasing survival is reflected in an advancing mean age of white patients with thalassemia major (25 years, up from 11 years in 1974). The results of the non-TCRN thalassemia survey confirm these observations and describe a young multiethnic thalassemia population distributed throughout North America. Newborn-screening results suggest that thalassemia births in North America are increasing and reflect the change in genotype and phenotype observed in the TCRN populations. CONCLUSIONS: The epidemiology of thalassemia in North America reflects a heterogeneous group of diseases with new ethnicities, genotypes, and phenotypes. In these communities, physicians will need to provide education, prenatal diagnosis, counseling, and management of this newly diverse group of patients.
Assuntos
Talassemia/epidemiologia , Adolescente , Adulto , Distribuição por Idade , Criança , Pré-Escolar , Genótipo , Humanos , Lactente , Recém-Nascido , Pessoa de Meia-Idade , América do Norte/epidemiologia , Fenótipo , Talassemia/etnologia , Talassemia/genéticaRESUMO
Thalassemia syndromes, hemoglobinopathies characterized by anemia secondary to genetic defects of hemoglobin, are the most common of the genetic blood disorders. The prevalence and severity of the thalassemia syndromes are population dependent, with the type of thalassemia seen dependent on racial background. The health care provider must recognize the woman at highest risk for thalassemia and initiate appropriate screening and diagnostic testing. The specific thalassemia dictates the potential maternal, fetal, and neonatal consequences of anemia, red blood cell dysfunction, and systemic oxygenation issues. This article discusses normal globin chain synthesis, diagnostic testing for thalassemia, plan of management, and implications for the woman and fetus.