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1.
Rev Assoc Med Bras (1992) ; 66(9): 1277-1282, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33027458

RESUMO

INTRODUCTION: Microcytic anemias are very common in clinical practice, with iron deficiency anemia (IDA) and thalassemia minor (TT) being the most prevalent. Diagnostic confirmation of these clinical entities requires tests involving iron metabolism profile, hemoglobin electrophoresis, and molecular analysis. In this context, several discriminant indices have been proposed to simplify the differential diagnosis between IDA and TM. OBJECTIVE: The aim of this paper was to demonstrate the clinical relevance of the use of discriminant indices in individuals with microcytic anemia to simplify the differential diagnosis between iron deficiency anemia and minor thalassemia. METHODS: A bibliographic and cross-sectional search was performed in the PubMed, SciELO and LILACS databases, using the following descriptors: iron deficiency anemia, thalassemia minor, and differential diagnosis. RESULTS: More than 40 mathematical indices based on erythrocyte parameters have been proposed in the hematological literature in individuals with microcytosis. Green & King indexes (IGK), Ehsani index, and erythrocyte count (RBC) had excellent performances, especially when their efficacy was observed in adults and children. CONCLUSIONS: Confirmatory tests for differential diagnosis between IDA and TM require time-consuming and costly methods. Despite the excellent performances of IGK, Ehsani index, and RBC, none of them presented sufficient sensitivity and specificity to establish a diagnosis. However, they can provide a powerful additional tool for diagnostic simplification between IDA and TM.


Assuntos
Anemia Ferropriva , Talassemia beta , Anemia Ferropriva/diagnóstico , Estudos Transversais , Diagnóstico Diferencial , Índices de Eritrócitos , Humanos , Talassemia beta/diagnóstico
2.
Ann Hematol ; 99(6): 1209-1215, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32363417

RESUMO

The phenotype/genotype relationship of patients with transfusion-dependent thalassaemia (TDT) is particularly complex and variable, thus generating different levels of severity and of annual transfusion volume (ATV). In this study, we explored the role and the contribution of several factors potentially involved in determining mean ATV in a cohort of TDT patients which have been followed since long time. We collected data on one-hundred and twenty-seven patients with transfusion-dependent ß-thalassaemia followed at Rare Blood Cell Disease Unit, AORN Cardarelli Hospital. Age at first transfusion, genotype, spleen status (splenectomy or not), and mean soluble transferrin receptor (sTfR) were the parameters included in the analysis. At stepwise regression analysis which included all the parameters, only splenectomy and mean sTfR significantly predicted the mean ATV (F = 70.94, P < 0.0001, R2 = 0.540). Overall, our data may suggest that in patients with TDT, the measurement of sTfR level together with the spleen status could contribute, more accurately than genotype, to provide a basal evaluation of residual erythropoietic activity and mean ATV.


Assuntos
Transfusão de Eritrócitos/tendências , Esplenectomia/tendências , Talassemia beta/sangue , Talassemia beta/terapia , Adolescente , Adulto , Idoso , Criança , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Retrospectivos , Adulto Jovem , Talassemia beta/diagnóstico
3.
Ann Hematol ; 99(9): 2037-2046, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32436014

RESUMO

Cardiovascular complications account for a substantial increase in morbidity and mortality in beta-thalassemia patients. Many patients have structural heart disease, and some of them present with symptomatic heart failure (HF). Quality of life (QOL) of beta-thalassemia patients is lower than that of the general population. The aim of our study was to explore the relationship between HF stages and QOL in beta-thalassemia patients. Seventy-three consecutive adult beta-thalassemia patients took part in this cross-sectional study. Stages of HF, classified with increasing severity as A, B, and C, were determined based on ACC/AHA guidelines. QOL was assessed using the SF-36 questionnaire. Fifteen patients had stage C HF, twenty-eight had stage B HF, and the remaining were considered stage A patients, as beta thalassemia is a predisposing factor for HF. All QOL domains except for bodily pain were significantly lower in stage C patients than in stage A patients. Stage C patients had significantly lower QOL scores for physical functioning, role physical, and social functioning domains than stage B patients. Stage B patients' QOL differed from stage A patients only in the vitality domain. In the multiple regression analysis which took several demographic and clinical factors into account, stage of HF was the most important factor associated with QOL, and negatively and significantly related to five QOL domains, namely physical functioning, role physical, general health, social functioning, and vitality. In conclusion, QOL is negatively affected by the severity of heart failure in beta-thalassemia patients.


Assuntos
Insuficiência Cardíaca/epidemiologia , Insuficiência Cardíaca/psicologia , Qualidade de Vida/psicologia , Índice de Gravidade de Doença , Talassemia beta/epidemiologia , Talassemia beta/psicologia , Adulto , Estudos Transversais , Feminino , Grécia/epidemiologia , Insuficiência Cardíaca/diagnóstico , Humanos , Masculino , Pessoa de Meia-Idade , Talassemia beta/diagnóstico
4.
J Vasc Res ; 57(4): 206-212, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32396894

RESUMO

BACKGROUND: Atherosclerosis has been extensively studied in thalassemia major (TM) and sickle cell disease but not yet in ß thalassemia intermedia (TI). Previous studies concerned with TM were performed in children. TI patients usually live longer and, thus, are more prone to complications of atherosclerosis. AIM: In our study, we applied color Doppler for the determination of arterial conduit and flow velocities in ß TI patients. METHODS: For central circulation, we measured right and left middle cerebral arteries (MCAs) and basilar artery (BA) mean flow velocity (MFV), pulsatility index (PI), and peak systolic velocity (PSV) as well as carotid intimal media thickness, and to assess peripheral circulation, we studied ankle/brachial index and posterior and anterior tibial arteries' (ATA, PTA) pressure and PSV. This was applied for 30 adult TI patients and 20 age-, sex-, and ethnic group-matched controls. RESULTS: Transcranial Doppler findings among cases and controls showed that the MFV, PSV of MCAs, and PSV, PI, and MFV of the BA were statistically higher in cases than controls. A comparison between splenectomized and nonsplenectomized patients showed that total leukocyte count, platelet count, lactate dehydrogenase, ferritin, PSV and MFV of the left MCA were all statistically higher in splenectomized cases. Differences between males and females with TI with respect to laboratory and Doppler findings were all statistically insignificant except for intima media thickness, PTA pressure, ATA pressure, and PSV. CONCLUSION: More than one parameter should be applied to assess atherosclerosis in TI. There is evidence of an increased risk of central ischemia rather than peripheral ischemia in these patients.


Assuntos
Artéria Braquial/diagnóstico por imagem , Doenças das Artérias Carótidas/diagnóstico por imagem , Espessura Intima-Media Carotídea , Arteriosclerose Intracraniana/diagnóstico por imagem , Artéria Cerebral Média/diagnóstico por imagem , Doença Arterial Periférica/diagnóstico por imagem , Artérias da Tíbia/diagnóstico por imagem , Ultrassonografia Doppler em Cores , Ultrassonografia Doppler Transcraniana , Talassemia beta/complicações , Adolescente , Adulto , Velocidade do Fluxo Sanguíneo , Artéria Braquial/fisiopatologia , Doenças das Artérias Carótidas/etiologia , Doenças das Artérias Carótidas/fisiopatologia , Estudos de Casos e Controles , Circulação Cerebrovascular , Egito , Feminino , Humanos , Arteriosclerose Intracraniana/etiologia , Arteriosclerose Intracraniana/fisiopatologia , Masculino , Artéria Cerebral Média/fisiopatologia , Doença Arterial Periférica/etiologia , Doença Arterial Periférica/fisiopatologia , Valor Preditivo dos Testes , Fluxo Pulsátil , Fatores de Risco , Fatores Sexuais , Esplenectomia , Artérias da Tíbia/fisiopatologia , Adulto Jovem , Talassemia beta/diagnóstico , Talassemia beta/cirurgia
5.
Int J Cardiovasc Imaging ; 36(7): 1343-1349, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32346846

RESUMO

Thalassemia defined a spectrum of diseases characterized by reduced or absent production of one of the globin chains of hemoglobin. High iron deposition in the myocardium may cause functional impairment even before any changes in left ventricular (LV) ejection fraction. These impairments may appear as changes in strain values. Early detection of myocardial dysfunction is essential for improving survival and preventing further complications. Therefore, this study aims to evaluate the cardiac strain patterns by Feature Tracking -Cardiac Magnetic Resonance Imaging (FT-CMR) method and their correlation with T2* values as a new parameter in determining myocardial iron overload (MIO). In this retrospective investigation, ninety-one patients with B-thalassemia major included from May 2016 to July 2019. Twenty-three healthy subjects, also incorporated as a control group. CMR used to evaluate ventricular volumes, LVEF, and the amount of myocardial T2*. Moreover, Global Longitudinal Strain (GLS), Global Circumferential Strain (GCS), and Global Radial Strain (GRS) were measured and analyzed in both rights and left ventricles. Correlations of cardiac T2* with GLS, GCS, and GRS were evaluated. The optimal cutoff value of GLS for prediction of cardiac T2* < 20 ms (as an indicator of inadequate chelation) calculated as well. There were significant correlations between cardiac T2* with LV GLS, LV GCS, and right ventricular GLS (p < 0.05 for each one). Moreover, a significant difference detected between the group of TM - MIO and TM + MIO and control group in terms of GLS (p < 0.001). The optimal cutoff value of GLS for prediction of cardiac T2* < 20 ms was at - 16.5% with sensitivity and specificity of 73% and 63%, respectively. Our study demonstrates that strain values measured by FT and myocardial T2* values are correlated. FT-CMR can be considered as an efficient tool for early detection of iron deposition and its effects on cardiac tissue so that proper and timely modification could have applied to chelation therapy.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Ferro/sangue , Imagem Cinética por Ressonância Magnética , Miocárdio/metabolismo , Volume Sistólico , Função Ventricular Esquerda , Função Ventricular Direita , Talassemia beta/complicações , Adolescente , Adulto , Cardiomiopatias/sangue , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Diagnóstico Precoce , Feminino , Humanos , Interpretação de Imagem Assistida por Computador , Masculino , Valor Preditivo dos Testes , Prognóstico , Estudos Retrospectivos , Fatores de Tempo , Adulto Jovem , Talassemia beta/sangue , Talassemia beta/diagnóstico , Talassemia beta/terapia
6.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(3): 243-251, 2020 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-32128739

RESUMO

Beta-thalassemia is an autosomal recessive genetic disease as well as one of the single gene disorders whose molecular basis was first clarified. The disease is mainly distributed in tropical and subtropical areas including southern China. Children with beta-thalassemia major have no obvious symptoms at birth, but will usually die in early childhood due to severe anemia and lack of effective treatment. This disease can be prevented by prenatal diagnosis. Patients with severe anemia can survive for a long time with life-long standardized blood transfusion and iron removal therapy. Hematopoietic stem cell transplantation may cure the disease, and gene therapy also showed a promising prospect. Based on the phenotypic and genetic data of Chinese population, this article focuses on the clinical diagnosis and genetic consultation of beta-thalassemia, and summarizes the key points of clinical treatment and population prevention of beta-thalassemia in order to provide clinicians and laboratory personnel with a practical guidance for the clinical management of beta-thalassemia.


Assuntos
Guias de Prática Clínica como Assunto , Talassemia beta/diagnóstico , Talassemia beta/terapia , Transfusão de Sangue , Criança , China , Humanos , Diagnóstico Pré-Natal
7.
Gene ; 741: 144544, 2020 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-32165295

RESUMO

The Maldives is an archipelago of 407,660 people according to population census of 2014, made up of 20 atolls, which has one of the highest prevalence of ß-thalassemia worldwide. However, there is a dearth of studies related to ß-thalassemia in the Maldives; therefore, in this study, we aimed to investigate the genetic epidemiology of ß-thalassemia in Maldives. Blood samples were collected from 110,504 participants (1992-2015). Hemoglobin and RBC indices were measured on automated hematology analyzers. The quantitation of hemoglobin, HbA2, Hb F, and other abnormal Hb variants were assessed by HPLC. Molecular analysis was performed for the most common mutations in Southeast Asia for only 874 individuals either heterozygous or homozygous for these mutations using reverse dot blot hybridization. We screened 110,504 individuals for ß-thalassemia between 1992 and 2015, which is ~ 30% of the entire population. The ß-thalassemia carrier frequency was estimated to be 16.2%. Molecular diagnosis of 874 ß-thalassemia carriers/major was performed for the most common seven mutations in Southeast Asia; of these, 139 patients were diagnosed as ß-thalassemia major. This analysis showed that the most common mutations were IVS1 + 5G > C, (678; 77.6%), followed by the CD 30 (136; 15.6%). The least frequent mutation was FS8/9, (1, 0.001%), followed by IVS1 + 1G > T and CD15 (2; 0.2%). The frequency of ß-thalassemia varies significantly among the 20 different atolls in Maldives. This study is expected to improve genetic counseling, creating awareness, enhance premarital screening, and customize the prevention and treatment strategies based on the needs of each atoll.


Assuntos
Aconselhamento Genético , Epidemiologia Molecular , Globinas beta/genética , Talassemia beta/genética , Feminino , Genótipo , Hemoglobinas Anormais/genética , Heterozigoto , Humanos , Ilhas do Oceano Índico , Masculino , Programas de Rastreamento/métodos , Mutação , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
8.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(4): 378-383, 2020 Apr 10.
Artigo em Chinês | MEDLINE | ID: mdl-32219817

RESUMO

OBJECTIVE: To determine the composition and distribution of beta-thalassemia-associated genotypes in Liuzhou area of Guangxi, China. METHODS: From January to December 2017, 13 847 individuals who came for premarital examination, maternity examination or health check were recruited with informed consent. The subjects were analyzed by reverse dot blotting (RDB) for 17 common beta-thalassemia-associated variants among the Chinese population. Individuals with inconsistent results by blood test, electrophoresis, and RDB were subjected to Sanger sequencing to detect rare variants of the beta globin gene. RESULTS: In total 2098 individuals were found to harbor beta-thalassemia-associated variants, which included 2075 heterozygotes (98.90%), 12 compound heterozygotes (0.57%) and 11 homozygotes (0.52%). CD41-42 (48.43%) and CD17 (31.45%) were the most common variants. Three hundred and thirty eight-individuals were found to also carry heterozygous variants of the alpha globin gene, with the most common types being --SEA/aa, -a3.7/aa, aCSa/aa, -a4.2/aa. Through Sanger sequencing, rare genotypes such as beta-32/betaN, betaCD41-42/betaIVS-II-5 and betaCD30/betaN were detected. CONCLUSION: Liuzhou area has a high incidence of beta-thalassemia, but with a complex variant spectrum and clinical phenotypes different from other regions. Genetic counseling and prenatal diagnosis for the carrier population is crucial for the reduction of the related birth defects. Our result may provide valuable information for the prevention and control of beta-thalassemia in this area.


Assuntos
Genótipo , Globinas beta/genética , Talassemia beta/genética , China , Feminino , Aconselhamento Genético , Variação Genética , Humanos , Mutação , Gravidez , Diagnóstico Pré-Natal , alfa-Globinas/genética , Talassemia beta/diagnóstico
9.
Int J Cardiovasc Imaging ; 36(6): 1105-1112, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-32086653

RESUMO

We differentiated the left ventricle non-compaction (LVNC) from hypertrabeculated myocardium due to a negative remodeling in thalassemia intermedia (TI) patients applying linear and planimetric criteria and comparing the cardiovascular magnetic resonance (CMR) findings. CMR images were analyzed in 181 TI patients enrolled in the Myocardial Iron Overload in Thalassemia Network and 27 patients with proved LVNC diagnosis. The CMR diagnostic criteria applied in TI patients were: a modified linear CMR Petersen's criterion based on a more restrictive ratio of diastolic NC/C > 2.5 at segmental level and the combination of planimetric Grothoff's criteria (percentage of trabeculated LV myocardial mass LV-MM ≥ 25% of global LV mass and total LV-MMI NC ≥ 15 g/m2). Seventeen TI patients showed at least one positive NC/C segment. Compared to LVNC patients, these patients showed a lower frequency of segments with non-compaction areas (2.41 ± 1.33 vs 5.48 ± 2.26; P < 0.0001), significantly lower LV-MM NC percentage (10.99 ± 4.09 vs 28.20 ± 4.27%; P < 0.0001), LV-MMI (7.58 ± 4.86 vs 19.88 ± 5.02 g/m2; P < 0.0001) and extension of macroscopic fibrosis (0.44 ± 0.18 vs 4.65 ± 2.89; P = 0.004), and significantly higher LV ejection fraction (61.29 ± 5.17 vs 48.50 ± 17.55%; P = 0.016) and cardiac index (4.80 ± 1.49 vs 3.46 ± 1.11 l/min/m2; P = 0.002). No TI patient fulfilled the Grothoff's criteria. All TI patients with an NC/C ratio > 2.5 showed morphological and functional CMR parameters significantly different from the patients with a proved diagnosis of LVNC. Differentiation of LVNC from hypertrabeculated LV in ß-TI patients due to a negative heart remodeling depends on the selected CMR criterion. We suggest using planimetric Grothoff's criteria to improve the specificity of LVNC diagnosis.


Assuntos
Cardiomiopatias/diagnóstico por imagem , Imagem Cinética por Ressonância Magnética , Função Ventricular Esquerda , Remodelação Ventricular , Talassemia beta/complicações , Adulto , Biomarcadores/sangue , Cardiomiopatias/sangue , Cardiomiopatias/etiologia , Cardiomiopatias/fisiopatologia , Estudos de Casos e Controles , Bases de Dados Factuais , Diagnóstico Diferencial , Feminino , Fibrose , Humanos , Ferro/sangue , Miocárdio Ventricular não Compactado Isolado/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Miocárdio/metabolismo , Miocárdio/patologia , Variações Dependentes do Observador , Valor Preditivo dos Testes , Reprodutibilidade dos Testes , Adulto Jovem , Talassemia beta/sangue , Talassemia beta/diagnóstico
10.
Eur J Ophthalmol ; 30(3): 600-607, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31902243

RESUMO

PURPOSE: The purpose was to evaluate retinal vascular parameters by optical coherence tomography angiography in ß-thalassemia major patients. METHODS: Thirty-three patients with ß-thalassemia major (study group) and 29 healthy children (control group) were enrolled in the study. All subjects underwent a complete ocular examination. The mean foveal avascular zone, non-flow area, foveal avascular zone perimeter, acircularity index of foveal avascular zone, foveal density, the superficial capillary plexus, and deep capillary plexus were scanned using 6 × 6 mm optical coherence tomography angiography scans centered on the macula. Superficial capillary plexus and deep capillary plexus were also scanned centered on the optic disk. We collected data on histories of patients, and hemoglobin and ferritin were also studied from both groups. RESULTS: The mean age was 13.85 ± 4.69 years (range: 4-21 years) in ß-thalassemia major group and 12.59 ± 3.66 years (range: 6-18 years) in the control group. The mean foveal avascular zone value was 0.265 ± 0.11 mm2 in the study group and 0.296 ± 0.12 mm2 in the control group. The mean non-flow area value was 0.468 ± 0.12 mm2 in the study group and 0.479 ± 0.14 mm2 in the control group (p > 0.05). Differences in the mean values for foveal density and acircularity index were statistically significant between the study group and control group (p < 0.05, p = 0.026, and p = 0.026, respectively). Superficial capillary plexus and deep capillary plexus were not a significant difference between the study and control groups in 6 × 6 mm scans on macula and 4.5 × 4.5 mm scans on optic disk area (p > 0.05). Acircularity index was negatively correlated (r = -0.292, p = 0.026), and foveal density was positively correlated with hemoglobin (r = 0.292, p = 0.026). CONCLUSION: By using optical coherence tomography angiography, we detected foveal microvascular changes in young ß-thalassemia patients before significant ocular anomalies development.


Assuntos
Angiofluoresceinografia , Fóvea Central/irrigação sanguínea , Doenças Retinianas/diagnóstico , Vasos Retinianos/patologia , Tomografia de Coerência Óptica , Talassemia beta/diagnóstico , Adolescente , Criança , Pré-Escolar , Feminino , Humanos , Masculino , Microscopia com Lâmpada de Fenda , Acuidade Visual/fisiologia , Adulto Jovem
11.
J Clin Pathol ; 73(5): 278-282, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-31653757

RESUMO

AIMS: Thalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and ß-thalassemia in the Quanzhou region of Fujian province, a city with high incidence of thalassemia in Southeast China. METHODS: A total of 11 668 cases were collected in Quanzhou region from January 2013 to June 2019. The deletions of α-thalassemia were detected by Gap-PCR, α-thalassemia and ß-thalassemia mutations were detected by DNA reverse dot blot hybridisation. Rare thalassemia gene testing and DNA sequencing were performed to detect rare and novel thalassemia mutation for suspected rare thalassemia carriers. RESULTS: Among 11 668 subjects, 4796 (41.10%) subjects were diagnosed with thalassemia. 3298 (28.27%) subjects were α-thalassemia carriers, 26 types of α-thalassemia mutations were identified, with the common α-thalassemia genotypes being --SEA/αα (71.47%), -α3.7/αα (17.13%) and -α4.2/αα (3.49%). 1407 (12.06%) subjects were ß-thalassemia carriers, 18 types of ß-thalassemia mutations were identified. The common five genotypes of ß-thalassemia were ßIVS-II-654/ßN (36.53%), ßCD41-42/ßN (30.28%), ßCD17/ßN (17.13%), ßCD26/ßN (5.12%) and ß-28/ßN (4.62%). Additionally, 91 (0.78%) subjects with composite α-thalassemia and ß-thalassemia were identified. Furthermore, 9 α-thalassemia and ß-thalassemia gene mutations (CAP +40-43 (-AAAC), IVS-I-1 (G>T), IVS-I-5 (G>C), SEA-HPFH, CD53 (-T), CD37 (A>G), -90 (C>T), CD3 (T>C), -α6.9) were identified for the first time in the region. Among them, CD53 (-T), CD37 (A>G) and -90 (C>T) mutations were identified for the first time in Fujian province. Moreover, CD3 (T>C), -α6.9 mutations were first identified in Chinese individual. CONCLUSIONS: Quanzhou region of South China has high incidence of thalassemia mutations. In this study, several cases of rare thalassemia mutations have been identified, providing reference for clinical consultation. The completion of this study is of great significance to strengthen the prevention and control of thalassaemia in the Quanzhou region.


Assuntos
Mutação , Talassemia alfa/genética , Talassemia beta/genética , Adolescente , Adulto , China , Feminino , Marcadores Genéticos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Análise de Sequência de DNA , Adulto Jovem , Talassemia alfa/diagnóstico , Talassemia alfa/epidemiologia , Talassemia beta/diagnóstico , Talassemia beta/epidemiologia
12.
PLoS One ; 14(12): e0216020, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31830127

RESUMO

BACKGROUND: The diagnosis of sickle cell disease (SCD) is made by hemoglobin assays such as high-performance liquid chromatography (HPLC), isoelectric focusing and cellulose acetate or citrate agar electrophoresis. These assays are easy to perform and used in large-scale newborn screening in many countries. These tests however may not easily differentiate Sß0 thalassemia from SS or identify other hemoglobin variants, and in this case, hemoglobin (HBB) gene sequencing may be necessary. OBJECTIVES: To develop a high throughput DNA based confirmatory assay for SCD and to detect mutations in the HBB gene. METHODS: We developed an automated pyrosequencing technique (PyS) based on QIAGEN technology (Hilden, Germany) to detect homozygous or heterozygous hemoglobin S mutations as well as hemoglobin C mutations. The technique was tested on 2,748 samples from patients enrolled in a multi-center SCD cohort in Brazil. Patients were previously tested using HPLC to diagnose SCD as part of routine clinical care. Any subjects with discrepant results between HPLC and PyS or with heterozygous hemoglobin S detected had Sanger sequencing of the HBB gene. RESULTS: We identified 168 samples with discrepant results between HPLC and PyS and 100 with concordant PyS = heterozygous S and HPLC, which would suggest SB-thalassemia or other heterozygous S variants. The PyS assay correctly identified 1906 (98.7%) of the 1930 HbSS and 628 (98.7%) of the 636 HbSC samples. Of the 179 remaining samples, PyS correctly indicated S heterozygosis in 165 (92.2%). Of the 165 heterozygous S samples confirmed by Sanger as consistent with Sß thalassemia genotype, 84 samples were classified as Sß0 thalassemia and 81 as Sß+ thalassemia. The most frequent beta thalassemia mutations of Sß0 and Sß+ were HBB: c.118C>T (Gln40Stop) and HBB c.92 + 6T> C, respectively. DISCUSSION: The PyS proved to be satisfactory for large-scale confirmatory testing of hemoglobin mutation. Moreover, with this study we were able to describe the most common ß+ and ß0 mutations in SCD patients with Sß-thalassemia in a large multi-institutional SCD cohort in Brazil.


Assuntos
Anemia Falciforme/diagnóstico , Hemoglobina Falciforme/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Mutação , Talassemia beta/diagnóstico , Anemia Falciforme/epidemiologia , Anemia Falciforme/genética , Brasil/epidemiologia , Estudos de Coortes , Genótipo , Humanos , Talassemia beta/epidemiologia , Talassemia beta/genética
13.
Indian Pediatr ; 56(10): 845-848, 2019 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-31724541

RESUMO

OBJECTIVE: In light of the recommendation of folic acid supplementation in chronic hemolytic anemia, with possible supratherapeutic dosing and associated side effects, we performed this study to investigate serum folate levels in children with chronic hemolytic anemia. METHODS: Phase 1 was a cross-sectional study of 134 patients in the Pediatric Hematology service, documenting daily dosage and performing serum folate levels. In phase 2, we reduced the dose to 1 mg for 148 patients and repeated the testing after six months. RESULTS: We found very high serum folate levels with Phase 1, with 93.2% above the upper level of normal. In Phase 2, values remained high with 42.5% above the acceptable upper limit. CONCLUSION: Doses of folic acid given to sickle cell and thalassemia patients exceed their actual needs. This should be re-evaluated to strike a balance between benefit and harm, with close monitoring of serum folate levels.


Assuntos
Anemia Falciforme/tratamento farmacológico , Suplementos Nutricionais , Ácido Fólico/administração & dosagem , Talassemia beta/tratamento farmacológico , Anemia Hemolítica/sangue , Anemia Hemolítica/diagnóstico , Anemia Hemolítica/tratamento farmacológico , Anemia Falciforme/sangue , Anemia Falciforme/diagnóstico , Criança , Doença Crônica , Estudos Transversais , Relação Dose-Resposta a Droga , Esquema de Medicação , Feminino , Humanos , Masculino , Prognóstico , Medição de Risco , Arábia Saudita , Estatísticas não Paramétricas , Resultado do Tratamento , Talassemia beta/sangue , Talassemia beta/diagnóstico
14.
J Assist Reprod Genet ; 36(12): 2515-2523, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31758512

RESUMO

PURPOSE: To investigate the validity, accuracy, and clinical outcomes of Karyomapping in preimplantation genetic testing (PGT) for ß-thalassemia combined with human leukocyte antigen (HLA) matching. METHODS: A total of 128 cycles from January 2014 to December 2017 were identified, and 1205 embryos were biopsied. The case group included 88 cycles using Karyomapping for PGT-HLA, compared with 40 cycles using polymerase chain reaction-short tandem repeat (PCR-STR) as the control group. RESULTS: There were significant differences in the HLA matching rate (21.34 vs. 14.37%), the matched transferable embryo rate (9.79 vs. 14.07%), the clinical pregnancy rate (65.08 vs. 41.86%), and the spontaneous miscarriage rate (2.44 vs. 22.22%) between the case and control groups. In the case group, nearly 1/3 (33.37%) of the embryos showed aneuploidy. According to the results of single nucleotide polymorphism (SNP) haplotype analysis, the recombination rates of HBB (hemoglobin subunit beta) and HLA were 11.46% and 5.61% respectively. HLA gene recombination was mostly distributed between HLA-A and HLA-B and the downstream region of HLA-DQB1. In addition, STR analysis could be considered in the case of copy-neutral loss of heterozygosity (LOH) in the region where the HLA gene is located. CONCLUSION: Karyomapping contributes to accurate selection of matched embryos, along with aneuploidy screening. However, STRs assist identification in cases of LOH in the target region.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cariotipagem/métodos , Diagnóstico Pré-Implantação , Talassemia beta/diagnóstico , Adulto , Biópsia , Transferência Embrionária , Feminino , Cadeias beta de HLA-DQ/genética , Subunidades de Hemoglobina/genética , Humanos , Perda de Heterozigosidade/genética , Gravidez , Taxa de Gravidez , Talassemia beta/genética , Talassemia beta/patologia
15.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 36(11): 1090-1093, 2019 Nov 10.
Artigo em Chinês | MEDLINE | ID: mdl-31703132

RESUMO

OBJECTIVE: To assess the value of next-generation sequencing (NGS)-based single nucleotide polymorphism (SNP) haplotyping for preimplantation genetic diagnosis (PGD) for beta-thalassemia coupled with human leukocyte antigen (HLA) matching. METHODS: Three couples were recruited. Couple 1 both carried a ß (IVS-2-654) variation and had previously given birth to a son with ß thalassemia major. Couple 2 respectively carried (cd41-42) and ß (IVS-2-654) but had no history of pregnancy. Couple 3 respectively carried ß (CD17) and ß (IVS-2-654), and had a daughter carrying ß (CD17). RESULTS: For couple 1, NGS-SNP typing identified two embryos not only unaffected with thalassemia but also with matched HLA. One blastocyst was transferred and resulted in successful pregnancy. A healthy baby was born at 39th week of gestation. Its umbilical blood was used to treat the sick brother through hemopoietic stem cell transplantation. For couple 2, seven blastocysts were obtained. Second transplantation has resulted in successful pregnancy. Prenatal diagnosis was consistent with PGD. For couple 3, two blastocysts not only unaffected with thalassemia but also with no pathogenic copy number variations were obtained. Transfer of one blastocyte resulted in successful pregnancy, and prenatal diagnosis was consistent with PGD. CONCLUSION: NGS-based SNP typing is an useful tool for selecting embryos unaffected with beta-thalassemia and matched HLA through PGD.


Assuntos
Antígenos HLA/genética , Polimorfismo de Nucleotídeo Único , Diagnóstico Pré-Implantação , Talassemia beta/diagnóstico , Variações do Número de Cópias de DNA , Feminino , Fertilização In Vitro , Haplótipos , Sequenciamento de Nucleotídeos em Larga Escala , Humanos , Masculino , Gravidez , Talassemia beta/genética
16.
Invest Ophthalmol Vis Sci ; 60(12): 3887-3896, 2019 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-31529120

RESUMO

Purpose: To investigate foveal avascular zone (FAZ) changes in the superficial (SCP) and deep (DCP) capillary plexuses in beta-thalassemia major (BTM) patients, as shown in optical coherence tomography angiography. Methods: Nonrandomized, comparative case series of 54 eyes of 27 BTM patients and 46 eyes of 23 healthy controls, utilizing an automated FAZ detection algorithm. Measurements included FAZ area and FAZ shape descriptors (convexity, circularity, and contour temperature). Results were compared between the two groups, and correlated to iron load and chelation therapy parameters. Results: SCP and DCP FAZ area were not significantly different between the control and BTM groups (P = 0.778 and P = 0.408, respectively). The same was true regarding SCP FAZ convexity (P = 0.946), circularity (P = 0.838), and contour temperature (P = 0.907). In contrast, a statistically significant difference was detected between controls and BTM group regarding DCP FAZ convexity (P = 0.013), circularity (P = 0.010), and contour temperature (P = 0.014). Desferrioxamine dosage was strongly correlated to the DCP area (r = 0.650, P = 0.05) and liver magnetic resonance imaging/T2-star to DCP circularity (r = -0.492, P = 0.038). Correlations were also revealed between urine Fe excretion and DCP convexity (r = 0.531, P = 0.019), circularity (r = 0.661, P = 0.002), and contour temperature (r = -0.591, P = 0.008). Conclusions: Retinal capillary plexuses and especially DCP seem to present unique morphologic changes in BTM patients, not in the FAZ area, but in specific shape descriptors, indicating minor but detectable FAZ changes. These changes correlate well with iron load and chelation therapy parameters. Their clinical importance and pathophysiologic implications remain to be elucidated through further studies.


Assuntos
Fóvea Central/irrigação sanguínea , Vasos Retinianos/patologia , Talassemia beta/diagnóstico , Adulto , Capilares/patologia , Desferroxamina/administração & dosagem , Feminino , Ferritinas/sangue , Angiofluoresceinografia/métodos , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Vasos Retinianos/diagnóstico por imagem , Sideróforos/administração & dosagem , Tomografia de Coerência Óptica/métodos , Talassemia beta/sangue , Talassemia beta/tratamento farmacológico
17.
Hemoglobin ; 43(3): 210-213, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31456457

RESUMO

The evaluation of a 10-month-old girl of Sicilian origin with a clinical phenotype of severe thalassemia led to the identification of two ß-globin gene defects, a ß-thalassemia (ß-thal), mutation at IVS-I-110 (HBB: c.93-21G>A) and a variant hemoglobin (Hb) mutation at codon 114 (HBB: c.344T>C) on the other allele, reported as Hb Durham-N.C. (also known as Hb Brescia) [ß114(G16)Leu→Pro] in the HbVar database. A very low Hb level (Hb 3.5 g/dL), microcytosis [mean corpuscular volume (MCV) 63.2 fL] and hypocromia [mean corpuscular Hb (MCH) 19.6 pg], increased red blood cell (RBC) distribution width (RDW) (36.0%), higher reticulocytes (6.2%), anisocytosis, poikilocytosis, hypocromia, basophilic stippling and inclusion body formation, were present in the affected subject. Analysis of other family components showed the presence of HBB: c.93-21G>A defect in the mother and in her brother, while Hb Durham-N.C. was absent in all other relatives, thus, this mutation has arisen as a de novo defect. This is the first case described as a severe thalassemic phenotype in a compound heterozygote carrier of this unstable Hb and a common ß-thalassemic allele. The important information gained from this case is that a rare dominant or recessive mutation may arise in every individual, even if this is a very rare event.


Assuntos
Alelos , Substituição de Aminoácidos , Heterozigoto , Mutação , Fenótipo , Globinas beta/genética , Talassemia beta/diagnóstico , Talassemia beta/genética , Biomarcadores , Análise Mutacional de DNA , Índices de Eritrócitos , Feminino , Humanos , Lactente , Talassemia beta/sangue
18.
Hemoglobin ; 43(3): 155-161, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31379233

RESUMO

ß-Thalassemia (ß-thal), is an inherited blood disorder caused by reduced or absent synthesis of ß-globin chains leading to imbalance of globin chain synthesis. The clearance of ß-thalassemic abnormal red blood cells (RBCs) that result from excessive unbound α-globin is mainly achieved by activated monocytes. The phagocytic activity of ß-thal monocytes significantly increases when co-cultured with normal and ß-thal RBC individuals compare to that of normal monocytes co-cultured with normal RBCs. The present study indicates that microRNA (miR) plays a role in monocyte activation. In this study, we identified the higher miR-125b expression in CD14 marker-positive monocytic cells of ß-thal patients. Moreover, miR-125b expression levels positively correlate with the phagocytic activity of monocytes. Remarkably, miR-125b expression levels are negatively correlated with RBC count, hemoglobin (Hb) and hematocrit [or packed cell volume (PCV)], which are the indices for the severity of anemia. From these findings, our future studies will be to prove the hypothesis that miR-125b expression in activated monocytes may be a genetic modifier related to the severity of anemia in ß-thal patients.


Assuntos
Anemia/sangue , MicroRNAs/genética , Monócitos/metabolismo , Fagocitose/genética , Talassemia beta/sangue , Talassemia beta/genética , Adolescente , Alelos , Anemia/diagnóstico , Anemia/etiologia , Biomarcadores , Criança , Índices de Eritrócitos/genética , Feminino , Humanos , Masculino , Mutação , Globinas beta/genética , Talassemia beta/complicações , Talassemia beta/diagnóstico
19.
Int J Low Extrem Wounds ; 18(3): 339-341, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31409160

RESUMO

Leg ulcers may occur due to many autoimmune, hereditary, inflammatory, and infectious causes including venous, arterial, and neuropathic ulcers. Hyperhomocysteinemia is a metabolic disorder caused by various enzyme defects in methionine metabolism. The most common cause is methylenetetrahydrofolatreductase (MTHFR) enzyme gene mutations. Hyperhomocysteinemia is an independent risk factor for deep vein thrombosis and peripheral arterial disease. The effects of endothelial cell damage on smooth muscle hypertrophy, platelet aggregation, coagulation, and fibrinolysis cause atherogenesis and thrombosis, leading to venous and arterial lower extremity ulcers. In this article, we report the case of a 47-year-old male patient who was admitted to our clinic due to painful leg ulcers that started 1 year ago. He had a history of vena cava inferior thrombosis, deep vein thrombosis, and 40 pack-year smoking. Histopathological examination of punch biopsy taken from ulcerative lesion showed intense inflammatory infiltration in the middle dermis, erythrocyte extravasation, leukocytoclasia, and thrombus formation in a small diameter venule lumen. There were nonspecific findings in direct immunofluorescence examination. He was found as having MTHFR C677T homozygote and plasminogen activator inhibitor-1 4G/5G heterozygote gene mutation with high homocysteine level of 22.90 µmol/L, and he was diagnosed as hyperhomocysteinemia. He was recommended to quit smoking because it triggered thrombosis in hyperhomocysteinemia. Herein, we present a case of hyperhomocysteinemia due to MTHFR mutation, which is one of the rare hereditary thrombophilia causes.


Assuntos
Enoxaparina/administração & dosagem , Hiper-Homocisteinemia , Úlcera da Perna , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Inibidor 1 de Ativador de Plasminogênio/genética , Compostos de Prata/administração & dosagem , Trombose Venosa , Talassemia beta , Bandagens , Biópsia/métodos , Diagnóstico Diferencial , Fibrinolíticos/administração & dosagem , Humanos , Hiper-Homocisteinemia/complicações , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/genética , Úlcera da Perna/sangue , Úlcera da Perna/etiologia , Úlcera da Perna/patologia , Úlcera da Perna/terapia , Masculino , Pessoa de Meia-Idade , Mutação , Trombofilia/diagnóstico , Trombofilia/etiologia , Trombose Venosa/complicações , Trombose Venosa/diagnóstico , Cicatrização , Talassemia beta/complicações , Talassemia beta/diagnóstico
20.
Hemoglobin ; 43(3): 174-181, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31411089

RESUMO

ß-Thalassemia (ß-thal) is the most common hereditary genetic blood disorder. The aims of this study were: (i) to determine the mutation types and the frequency of these mutations in ß-thal patients to obtain the ethnic origins of the population in Siirt Province; (ii) to evaluate the pathogenicity of these mutations by performing in silico analysis; (iii) to reveal the genotype-phenotype correlation by comparing the clinical manifestation of our patients to the specific mutations in this population. This study included 34 patients (18 males and 16 females) with a mean age of 9.1 ± 3.6 years (range 3-16 years). All mutations were determined using sequence analysis methods, and the mutations were analyzed using bioinformatics tools. Thirteen different mutations were detected in the patients: IVI-I-110 (G>A) (HBB: c.93-21G>A) (38.9%); IVS-II-1 (G>A) (HBB: c.315_1G>A) (11.1%); -30 (T>A) (HBB: c.-80T>A) (9.25%) and IVS-I-1 (G>A) (HBB: c.92 + 1G>A) (9.25%), were the most common, and these mutations constituted 68.5% of the cases. Missense codon 6 (A>T) (HBB: c.20A>T) was not pathogenic; however, all the intronic mutations (IVS-I-1, IVS-I-110, IVS-II-1) and frameshift mutations [codon 44 (-C) (HBB: c.135delC) and codons 36/37 (-T) (HBB: c.112delT)] resulted in disease. These mutations can be used to determine the ethnic origin of the Siirt population and, in affected pregnant women, to develop prenatal strategies. A fatal phenotype can be identified by in silico analysis; however, mutations that are unknown prior to marriage, pregnancy, and childbirth or new mutations can be less accurately identified.


Assuntos
Genética Populacional , Mutação , Globinas beta/genética , Talassemia beta/epidemiologia , Talassemia beta/genética , Adolescente , Alelos , Sequência de Aminoácidos , Substituição de Aminoácidos , Criança , Pré-Escolar , Códon , Grupos Étnicos/genética , Feminino , Frequência do Gene , Estudos de Associação Genética , Genótipo , Humanos , Masculino , Modelos Moleculares , Fenótipo , Conformação Proteica , Turquia/epidemiologia , Globinas beta/química , Talassemia beta/diagnóstico
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