- 作者列表："Bender MA","Yusuf C","Davis T","Dorley MC","Del Pilar Aguinaga M","Ingram A","Chan MS","Ubaike JC","Hassell K","Ojodu J","Hulihan M
:Alpha-thalassemia comprises a group of inherited disorders in which alpha-hemoglobin chain production is reduced. Depending on the genotype, alpha-thalassemia results in moderate to profound anemia, hemolysis, growth delays, splenomegaly, and increased risk for thromboembolic events; certain patients might require chronic transfusions. Although alpha-thalassemia is not a core condition of the United States Recommended Uniform Screening Panel* for state newborn screening programs, methodologies used by some newborn screening programs to detect sickle cell disease, which is a core panel condition, also detect a quantitative marker of alpha-thalassemia, hemoglobin (Hb) Bart's, an abnormal type of hemoglobin. The percentage of Hb Bart's detected correlates with alpha-thalassemia severity. The Association of Public Health Laboratories' Hemoglobinopathy Workgroup conducted a survey of state newborn screening programs' alpha-thalassemia screening methodologies and reporting and follow-up practices. Survey findings indicated that 41 of 44 responding programs (93%) report some form of alpha-thalassemia results and 57% used a two-method screening protocol. However, the percentage of Hb Bart's used for thalassemia classification, the types of alpha-thalassemia reported, and the recipients of this information varied widely. These survey findings highlight the opportunity for newborn screening programs to revisit their policies as they reevaluate their practices in light of the recently released guideline from the Clinical and Laboratory Standards Institute (CLSI) on Newborn Screening for Hemoglobinopathies (1). Although deferring to local programs for policies, the report used a cutoff of 25% Hb Bart's in its decision tree, a value many programs do not use. Standardization of screening and reporting might lead to more timely diagnoses and health care services and improved outcomes for persons with a clinically significant alpha-thalassemia.
Α-地中海贫血包括一组遗传性疾病，其中 α-血红蛋白链产生减少。根据基因型，α-地中海贫血导致中度至重度贫血、溶血、生长延迟、脾肿大和血栓栓塞事件风险增加; 某些患者可能需要长期输血。虽然 α-地中海贫血不是美国推荐的州新生儿筛查项目的统一筛查小组 * 的核心条件，但一些新生儿筛查项目用于检测镰状细胞病的方法，这是一个核心小组条件，也检测 α-地中海贫血的定量标记物血红蛋白 (Hb) bart's，一种异常类型的血红蛋白。检测到的Hb Bart百分比与 α-地中海贫血严重程度相关。公共卫生实验室协会血红蛋白病工作组对州新生儿筛查项目的 α-地中海贫血筛查方法以及报告和随访实践进行了调查。调查结果表明，44个应答项目中的41个 (93%) 报告了某种形式的 α-地中海贫血结果，57% 使用了两种方法的筛查方案。然而，用于地中海贫血分类的Hb Bart's的百分比、报告的 α-地中海贫血的类型以及该信息的接受者差异很大。这些调查结果强调了新生儿筛查项目重新审视其政策的机会，因为他们根据临床和实验室标准协会 (CLSI) 最近发布的新生儿血红蛋白病筛查指南 (1) 重新评估其实践。尽管在政策上推迟了当地的项目，该报告在决策树中使用了25% Hb Bart的截止值，这是许多程序不使用的值。筛查和报告的标准化可能导致更及时的诊断和医疗保健服务，并改善具有临床意义的 α-地中海贫血患者的结局。
METHODS:BACKGROUND:Thalassemia is one of the most common monogenetic diseases in the south of China and Southeast Asia. Hemoglobin Bart's hydrops fetalis syndrome was caused by a homozygous Southeast Asian deletion (-/-) in the HBA gene. Few studies have proved the potential of screen for Bart's hydrops fetalis using fetal cell-free DNA. However, the number of cases is still relatively small. Clinical trials of large samples would be needed. OBJECTIVE:In this study, we aimed to develop a noninvasive method of target-captured sequencing and genotyping by the Bayesian method using cell-free fetal DNA to identify the fetal genotype in pregnant women who are at risk of having hemoglobin Bart hydrops fetalis in a large-scale study. STUDY DESIGN:In total, 192,173 couples from 30 hospitals were enrolled in our study and 878 couples were recruited, among whom both the pregnant women and their husbands were detected to be carriers of Southeast Asian type (-/αα) of α-thalassemia. Prenatal diagnosis was performed by chorionic villus sampling, amniocentesis, or cordocentesis using gap-polymerase chain reaction considered as the golden standard. RESULTS:As a result, we found that the sensitivity and specificity of our noninvasive method were 98.81% and 94.72%, respectively, in the training set as well as 100% and 99.31%, respectively, in the testing set. Moreover, our method could identify all of 885 maternal samples with the Southeast Asian carrier and 36 trisomy samples with 100% of sensitivity in T13, T18, and T21 and 99.89% (1 of 917) and 99.88% (1 of 888) of specificity in T18 and T21, respectively. CONCLUSION:Our method opens the possibility of early screening for maternal genotyping of α-thalassemia, fetal aneuploidies in chromosomes 13/18/21, and hemoglobin Bart hydrops fetalis detection in 1 tube of maternal plasma.
METHODS:OBJECTIVES:Sickle cell disease (SCD) is a serious illness with disabling acute and chronic pain that needs better therapies, but insufficient patient participation in research is a major impediment to advancing SCD pain management. The purpose of this article is to discuss the challenges of conducting an SCD study and approaches to successfully overcoming those challenges. DESIGN:In a repeated-measures, longitudinal study designed to characterize SCD pain phenotypes, we recruited 311 adults of African ancestry. Adults with SCD completed 4 study visits 6 months apart, and age- and gender-matched healthy controls completed 1 visit. RESULTS:We recruited and completed measures on 186 patients with SCD and 125 healthy controls. We retained 151 patients with SCD with data at 4 time points over 18 months and 125 healthy controls (1 time point) but encountered many challenges in recruitment and study visit completion. Enrollment delays often arose from patients' difficulty in taking time from their complicated lives and frequent pain episodes. Once scheduled, participants with SCD cancelled 49% of visits often because of pain; controls canceled 30% of their scheduled visits. To facilitate recruitment and retention, we implemented a number of strategies that were invaluable in our success. CONCLUSION:Patients' struggles with illness, chronic pain, and their life situations resulted in many challenges to recruitment and completion of study visits. Important to overcoming challenges was gaining the trust of patients with SCD and a participant-centered approach. Early identification of potential problems allowed strategies to be instituted proactively, leading to success.
METHODS:OBJECTIVES:Sickle cell anemia is the commonest genetic disorder in India, and the frequency of the sickle cell gene is very high in the remote tribal areas where facilities are generally limited. Therefore, a rapid and affordable point-of-care test for sickle cell disease is needed. METHODS:The diagnostic accuracy of HemoTypeSC was evaluated against automated high-performance liquid chromatography (HPLC) as the gold standard for its efficacy in a newborn screening program. RESULTS:A total of 1,559 individuals (980 newborns and 579 adults) from four participating centers were analyzed by both methods. HemoTypeSC correctly identified 209 of 211 total hemoglobin (Hb) SS cases, for a 99.1%/99.9% total HbSS sensitivity/specificity. Overall, HemoTypeSC exhibited sensitivity and specificity of 98.1% and 99.1% for all possible phenotypes (HbAA, HbAS, and HbSS) detected. HPLC is relatively expensive and not available in most laboratories in remote tribal areas. CONCLUSIONS:We conclude that the rapid, point-of-care testing device HemoTypeSC test is suitable for population and newborn screening for the HbS phenotype.