Search results for: thalassemia

Authors: Ha T. T. Ly, Truc B. Truc, Hai N. Truong, Mai P. T. Nguyen, Ngoc D. Ngo, Khanh V. Tran, Hai T. Le

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Beta thalassemia is one of the most common inherited blood disorders, which is characterized by decreased or absent in beta globin expression. Patients with Beta thalassemia whose anemia is not so severe as to necessitate transfusions are said to have thalassemia intermedia. Objective: The goal of this study is prenatal diagnosis for pregnancy woman with Beta thalassemia intermedia and her husband with Beta thalassemia carrier at high risk of Beta thalassemia major in Northern of Vietnam. Material and method: The family has a 6 years-old compound heterozygous thalassemia major for CD71/72(+A) and Hbb:c. -78A>G/nt-28(A>G) male child. The father was heterozygous for CD71/72(+A) mutation which is Beta plus type and the mother was compound heterozygosity of two different variants, namely, Hbb: c. -78A>G/nt-28(A>G) and CD26(A-G) HbE. Prenatal Beta thalassemia mutation detection in fetal DNA was carried out using multiplex Amplification-refractory mutation system ARMS-PCR and confirmed by direct Sanger-sequencing Hbb gene. Prenatal diagnoses were perfomed by amniotic fluid sampling from pregnant woman in the 16-18th week of pregnancy after the genotypes of parents of the probands were identified. Result: When amniotic fluid sample was analyzed for Beta globin gene (Hbb), we found that the genotype is heterozygous for CD71/72(+A) and CD26(A-G) HbE. This genotype is different from the 1st child of this family. Conclusion: Prenatal diagnosis helps the parents to know the genotype and the thalassemia status of the fetus, so they can have early decision on their pregnancy. Genetic diagnosis provided a useful method in diagnosis for familial members in pedigree, genetic counseling and prenatal diagnosis.

Keywords: beta thalassemia intermedia, Hbb gene, pedigree, prenatal diagnosis

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Authors: Shahira El Shafie, Hanaa Eldash, Engy Ghabbour, Mohamed Eid

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Several immunologic defects can be found in patients with beta-thalassemia, among which the impairment of neutrophil phagocytic function is of utmost importance. Attention has been directed to the role of proinflammatory cytokines in neutrophil chemotaxis and phagocytosis. Interleukin-8 (IL-8) is an important chemotactic and activation peptide for neutrophils; changes in IL-8 level and potential correlation with neutrophil function can be relevant to immunomodulation pathophysiology in beta-thalassemia patients. This case-control study aimed to evaluate IL-8 level and to assess granulocyte recruitment, as markers of immunomodulation, in poly-transfused thalassemia patients attending Fayoum University Hospitals. The study was conducted on 50 patients with ß thalassemia and 32 age-matched controls. 21/50 patients were transfused more than ten times, and 29/50 were transfused in a lower frequency. Patients and controls were subjected to thorough history taking and clinical examination, measurement of IL-8 level using human IL-8 ELISA kit, and Rebuck skin window technique (RSWT) to assess granulocyte recruitment. Our data showed statistically significant higher levels of IL-8 in ß thalassemia patients compared to control with a much higher difference in patients transfused more than ten times. Neutrophil recruitment was significantly lower in ß thalassemia patients compared to control at 4 hours and 24 hours test time. Although IL-8, the main chemotactic pro-inflammatory cytokine showed a higher level in thalassemia patients, neutrophils recruitment was significantly lower, especially in those receiving more than ten transfusion times. Our findings suggest a possible role of other neutrophil chemotactic factors, defective neutrophil response, or increased IL-8 as compensation of abnormal function. We recommend the use of IL-8 and Rebuck skin window technique as useful markers of immunomodulation in thalassemia and further study for these biomarkers to assess their clinical implications and impact on the management of thalassemia patients.

Keywords: beta-thalassemia, Interleukin-8, Rebuck skin window technique, immunomodulation

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Authors: Roohallah Yousefi

Abstract:

Introduction: In beta-thalassemia, an imbalance in the production of beta subunits of hemoglobin leads to the oxidation and deposition of excess alpha-globin chains at the cell membrane, resulting in the hemolysis of erythrocytes and a disorder of erythropoiesis. Antioxidants, such as curcumin, may promote this progression. This study aims to investigate the antioxidant effect of curcumin on hemolysate samples from patients with beta-thalassemia. Materials and methods: Pure curcumin was extracted and purified for use in studying its effect on the visual light absorbance of hemoglobin in hemolysate samples from beta-thalassemia patients compared to control samples. Changes in light absorbance at 540 and 700 nm wavelengths during exposure to curcumin were analyzed to examine the shift from oxyhemoglobin to deoxyhemoglobin. Results: Curcumin was found to dissolve rapidly and to a high degree in ethanol at 1 mg/ml, but did not dissolve in distilled water at the same concentration. The curcumin addition to the hemolysate sample of a patient with beta-thalassemia resulted in a decrease in the light absorbance of the sample at 540 nm wavelength, with minimal changes observed in the control sample. Conclusion: Curcumin deoxygenated the hemolysate samples from both the patient and control, causing hemoglobin precipitation to occur slowly. The study suggests a greater potential role for curcumin in deoxygenating hemoglobin in the hemolysate samples of beta-thalassemia patients compared to those of the normal control.

Keywords: beta-thalassemia, hemoglobin, curcumin, alpha-globin

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Authors: Sanober Khanum, Barerah Siddiqui, Asim Qidwai

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Objective: To determine the risk factors and frequency of depressive trends in children and adolescents suffering from Beta-Thalassemia. Background: Thalassemia is a chronic disease affecting 10,000 people in 60 countries. Many studies show that prolonged medical conditions cause depression. Due to the invasive procedures and suffering, Beta-Thalassemia cause great psychological distress to both children and their caregivers. The study shows 14-24% prevalence of psychiatric problems in Thalassemic patients. Method: Sample consisted of 195 registered patients of A.M.T.F (Female=95 and Male=100). Based on age range the sample was divided into two groups, Group A = children (4-9 years) and Group B = adolescent (10-16 years). A detailed interview with a self-made screening measure was administered on parents to find out the level of depression in patients. Statistics: Chi-square and t-test was applied in order to analyze the data. Results show high prevalence of depression, depression n= 131(66.83%), no depression n=65(33.16%). Analyses reflect that age influences the level of depression Adolescent (71.05%) and Children (64.16%). The analysis also shows a difference in level of depression between both genders. (t=2.975, p < .05). Conclusion: There is a high possibility of developing depressive trend in children affected with Beta Thalassemia; especially females. Therefore, there is a dire need for psychological screening and appropriate treatment in order to improve physical; as well as mental health.

Keywords: childhood depression, chronic illness, psychopathology, Thalassemia

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Authors: Mohamed H. Kosba, Heba A. Ibrahim, H. Rozita

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Statement of the Problem: The life expectancy for transfusion-dependent thalassemia patients has increased dramatically with iron-chelation therapy and other modern management modalities. In these patients, the most dominant maxillofacial manifestations are protrusion of zygomatic bones and premaxilla due to the hyperplasia of bone marrow. The purpose of this study is to determine the prevalence of malocclusion and orthodontic treatment needs according to the Dental Aesthetic Index (DAI) among Malay transfusion-dependent thalassemia patients. Orientation: This is a cross-sectional study consist of 43 Malay transfusion-dependent thalassemia patients, 22 males, and 19 females with the mean age of 15.9 years old (SD 3.58). The subjects were selected randomly from patients attending Paediatrics and Internal Medicine Clinic at Hospital USM and Hospital Sultana Bahiyah. The subjects were assessed for malocclusion according to Angle’s classification, and orthodontic treatment needs using DAI. The results show that 22 of the subjects (51.1%) have class II malocclusion, 12 subjects (28%) have class І, while 9 subjects (20.9%) have class Ⅲ. The assessment of orthodontic treatment needs to reveal 22 cases (51.1%) fall in the normal/minor needs category, 12 subjects (28%) fall in the severe and very severe category, while 9 subjects (20.9%) fall in the definite category. Conclusion & Significance: Half of Malay transfusion-dependent thalassemia patients have Class Ⅱmalocclusion. About 28% had malocclusion and required orthodontic treatment. This research shows that Malay transfusion-dependent thalassemia may require orthodontic management; earlier intervention to reduce the complexity of the treatment later, suggesting functional appliance as a suitable treatment option for them, a twin block appliance together with headgear to restrict maxillary growth suggested for management. The current protocol implemented by the Malaysian Ministry of Health for the management of these patients seems to be sufficient since the result shows that about 28% require orthodontic treatment need, according to DAI.

Keywords: prevalence, DAI, thalassaemia, angle classification

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Authors: Shervin Rashidinia, Sara Shahmoradi, Seyyed Shahin Eftekhari, Mohsen Talebizadeh, Mohammad Saleh Sadeghi

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Background: Beta-thalassemia Major (BTM) is a kind of hereditary hemolytic anemia which depended on regular monthly blood transfusion. However, iron deposition into the organs leads to multi-organ damage. The present study is the first study which aimed to evaluate the average of five-years serum ferritin level and compared by the prevalence of short stature and hypocalcemia. Materials/Methods: A cross-sectional retrospective study which a total of 140 patients with beta-thalassemia who were referred to Qom Thalassemia Clinic between February 2011 and July 2016 were enrolled to be reviewed. The exclusion criteria were consisting of incomplete medical records, diagnosis less than 2-years-ago and the blood transfusion less than every 4 weeks. The data including age, gender, weight, height, age of initial blood transfusion, age of initial chelation therapy, ferritin, and calcium were collected and analysis by SPSS version 24. Results: A total of 140 patients were enrolled. Of them, 75 (53.4%) were female. The mean age of the patients was 13.4±4.6 years.The mean age of initial diagnosis was 20.2±7.4 months. Hypocalcemia and short stature were occurred in 41 (29.3%) and 37 (26.4%) patients, respectively. The mean five-years serum ferritin level was significantly higher in the patients with short stature and hypocalcemia (P<0.0001). However, rise in serum ferritin level significantly increases the risk of short-stature and hypocalcemia (1.0004- and 1.0029 fold, respectively). Conclusion: We demonstrated that prevalence of short stature and hypocalcemia were significantly higher in the BTM.However, ferritin significantly increases the risk of short stature and hypocalcemia.

Keywords: beta-thalassemia, ferritin, growth retardation, hypocalcemia

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Authors: Sachiko Hosoya

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Objectives: The purpose of this paper is to investigate the social policy of preventive genetic medicine in Iran, by following the legalization process of abortion law and the factors affecting the process in wider Iranian contexts. In this paper, ethical discussions of prenatal diagnosis and selective abortion in Iran will be presented, by exploring Iranian social policy to control genetic diseases, especially a genetic hemoglobin disorder called Thalassemia. The ethical dilemmas in application of genetic medicine into social policy will be focused. Method: In order to examine the role of the policy for prevention of genetic diseases and selective abortion in Iran, various resources have been sutudied, not only academic articles, but also discussion in the Parliament and documents related to a court case, as well as ethnographic data on living situation of Thalassemia patients. Results: Firstly, the discussion on prenatal diagnosis and selective abortion is overviewed from the viewpoints of ethics, disability rights activists, and public policy for lower-resources countries. As a result, it should be noted that the point more important in the discussion on prenatal diagnosis and selective abortion in Iran is the allocation of medical resources. Secondly, the process of implementation of national thalassemia screening program and legalization of ‘Therapeutic Abortion Law’ is analyzed, through scrutinizing documents such as the Majlis record, government documents and related laws and regulations. Although some western academics accuse that Iranian policy of selective abortion seems to be akin to eugenic public policy, Iranian government carefully avoid to distortions of the policy as ‘eugenic’. Thirdly, as a comparative example, discussions on an Iranian court case of patient’s ‘right not to be born’ will be introduced. Along with that, restrictive living environments of people with Thalassemia patients and the carriers are depicted, to understand some disabling social factors for people with genetic diseases in the local contexts of Iran.

Keywords: abortion, Iran, prenatal diagnosis, public health ethics, Thalassemia prevention program

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Authors: Shenaz Ahmed, Hussain Jafri, Muhammed Faran, Wajeeha Naseer Ahmed, Yasmin Rashid, Yasmin Ehsan, Shabnam Bashir, Mushtaq Ahmed

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Low uptake of cascade screening for βeta-Thalassaemia Major (β-TM) in the ‘Punjab Thalassaemia Prevention Project’ (PTPP) in Pakistan led to the development of a ‘decision support intervention for relatives’ (DeSIRe). This paper presents the experiences of relatives of children with β-TM of the DeSIRe following its use by PTPP field officers in routine clinical practice. Fifty-four semi-structured qualitative interviews were conducted (April to June 2021) with relatives in seven cities in the Punjab province (Lahore, Sheikhupura, Nankana Sahab, Kasur, Gujranwala, Multan, and Faisalabad). Thematic analysis shows that participants were satisfied with the content of the DeSIRe and its delivery by the field officers in a family meeting. They understood the main purpose of the DeSIRe was to improve their knowledge of β-TM and its inheritance, to enable them to make decisions about thalassemia carrier testing, particularly before marriage. While participants raised concerns about the stigma of testing positive, they believed the DeSIRe was an appropriate intervention, which supported relatives to make informed decisions. Our findings show the DeSIRe is appropriate for use by healthcare professionals in routine practice in a low-middle income country and has the potential to facilitate shared decision-making about cascade screening for thalassemia. Further research is needed to prove the efficacy of the DeSIRe.

Keywords: thalassemia, Pakistan, cascade screening, decision support

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Authors: Amna Imtiaz

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Aims: To correlate serum ferritin with left ventricular function in beta thalassemia major patients with increased transfusion dependence and to find out whether echocardiography can be used to assess pre clinical cardiac disease in these patients. Methods: The cross sectional study was conducted at Department of Pathology, Shaheed Zulfiqar Ali Bhutto Medical University, Pakistan Institute of Medical Sciences, Islamabad. 60 patients of beta thalassemia major with increased transfusion dependence were enrolled in this study. Serum ferritin levels of all patients were measured by using indirect enzyme linked immunosorbent assay (ELISA). Echocardiography was performed on all patients by a consultant cardiologist by linking conventional echocardiography with tissue Doppler imaging. Ejection fraction and E/A ratio were measured in all patients to assess left ventricular systolic and diastolic function. Results: On the basis of serum ferritin level, patients were divided into three groups. Group I consisted of patients having serum ferritin level equal to or less than 2500 ng/ml. A total of 25 patients were placed in this group. Group II included patients having serum ferritin level between 2500 to 5000 ng/ml. A total of 22 patients were placed in this group. Group III included patients having serum ferritin level more than 5000 ng/ml. This group consisted of 13 patients. All patients having serum ferritin below 2500ng/ml had normal systolic function, and only 16% of the patients in this group had diastolic dysfunction as reflected by abnormal E/A ratio. In group II, 27% of the patients had systolic dysfunction reflected by subnormal ejection fraction while 40% of the patients had diastolic dysfunction. In group III, 62% of the patients had abnormal systolic and diastolic function. Pearson correlation was used to find a correlation between serum ferritin and left ventricular function. A strong negative correlation was found which is reflected by a p value of less than 0.05 which is significant. Chi square test is used to correlate serum ferritin with E/A ratio. P value came out to be less than 0.05 which is significant.

Keywords: beta thalassemia major, left ventricular function, serum ferritin, transfusion dependence

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Authors: Gehan Hussein, Hala Agha, Rasha Abdelraof, Marina George, Antoine Fakhri

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Background: β-Thalassemia major (TM) and sickle cell disease (SCD) are inherited hemoglobin disorders resulting in chronic hemolytic anemia. Cardiovascular involvement is an important cause of morbidity and mortality in these groups of patients. The narrow border is between overt myocardial dysfunction and clinically silent left ventricular (LV) and / or right ventricular (RV) dysfunction in those patients. 3 D Speckle tracking echocardiography (3D STE) is a novel method for the detection of subclinical myocardial involvement. We aimed to study myocardial affection in SCD and TM using 3D STE, comparing it with conventional echocardiography, correlate it with serum ferritin level and lactate dehydrogenase (LDH). Methodology: Thirty SCD and thirty β TM patients, age range 4-18 years, were compared to 30 healthy age and sex matched control group. Cases were subjected to clinical examination, laboratory measurement of hemoglobin level, serum ferritin, and LDH. Transthoracic color Doppler echocardiography, 3D STE, tissue Doppler echocardiography, and aortic speckle tracking were performed. Results: significant reduction in global longitudinal strain (GLS), global circumferential strain (GCS), and global area strain (GAS) in SCD and TM than control (P value <0.001) there was significantly lower aortic speckle tracking in patients with TM and SCD than control (P value< 0.001). LDH was significantly higher in SCD than both TM and control and it correlated significantly positive mitral inflow E, (p value:0.022 and 0.072. r: 0.416 and -0.333 respectively) lateral E/E’ (p value.<0.001and 0.818. r. 0.618 and -0. 044.respectively) and septal E/E’ (p value 0.007 and 0.753& r value 0.485 and -0.060 respectively) in SCD but not TM and significant negative correlation between LDH and aortic root speckle tracking (value 0.681& r. -0.078.). The potential diagnostic accuracy of LDH in predicting vascular dysfunction as represented by aortic root GCS with a sensitivity 74% and aortic root GCS was predictive of LV dysfunction in SCD patients with sensitivity 100% Conclusion: 3D STE LV and RV systolic dysfunction in spite of their normal values by conventional echocardiography. SCD showed significantly lower right ventricular dysfunction and aortic root GCS than TM and control. LDH can be used to screen patients for cardiac dysfunction in SCD, not in TM

Keywords: thalassemia major, sickle cell disease, 3d speckle tracking echocardiography, LDH

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Authors: Rongrong Liu, Li Wang, Hui Xu, Jianpei Fang, Sixi Liu, Xiaolin Yin, Junbin Liang, Gaohui Yan, Yaoyun Li, Yali Zhou, Xinyu Li, Yue Li, Lei Shi, Yongrong Lai, Junjiu Huang, Xinhua Zhang

Abstract:

Background: Beta-Thalassemia is caused by reduced (β+) or absent (β0) synthesis of the β-globin chains of hemoglobin. Transfusions and oral iron chelation therapy have improved the quality of life for patients with Transfusion-Dependent thalassemia (TDT). Recent advances in genome editing platforms of CRISPR-Cas9 have paved the way for induction of HbF by reactivating expression of γ-chain.Aims: We performed CRISPR-Cas9-mediated genome editing of hematopoietic stem cells to mutate HBG1/HBG2 promoter sequence, thereby representing a naturally occurring HPFH-liked mutation, producing RM-001. Here, we present an initial assessment of safety and efficacy of RM-001 in patients with TDT. Methods: Patients (6–35 y of age) with TDT receiving packed red blood cell (pRBC) transfusions of ≥100 mL/kg/y or ≥10 units/y in the previous 2 y were eligible. CD34+ cells were edited with CRISPR-Cas9 using a guide RNA specific for the binding site of BCL11A on the HBG1/2 promoter. Prior to RM-001 product infusion (day 0), patients received myeloablative conditioning with Busulfan from day-7 to day-4. Patients were monitored for AEs Hb expression.Results: Data cut as of 28 Feb 2024, 16 TDT patients have been treated with RM-001 and followed ≥3 months. 5 of these 16 patients had finished their 24 months follow up. Eleven patients have β0/β0 genotype and five patients have β0/β+ genotype. In addition to β-thalassemia, two patients had α- deletion with the genotype of --/αα. Efficacy:All patients received a single dose intravenous infusion of RM-001 cells. 5 of them had been followed 24 months or longer. All patients achieved transfusion-independent (TI, total Hb continued ≥ 9g/dL) (Figure1). Patients demonstrated sustained and clinically meaningful increases in HbF levels since 4 month post-RM-001 infusion (Figure.2). Total hemoglobin in all patients was stable at 10-12g/dL during the follow-up period. Safety:The adverse events observed after RM-001 infusion were consistent with those that are typical of Busulfan-based myeloablation. The allelic editing analysis at 6-month visit showed that the on-target allelic editing frequency in bone marrow cells was 73.44% (64.65% to 84.6%, n=13).Summary/Conclusion: This interim analysis, in which all the 19 patients age from 7.9 to 25yo met the success criteria for the trial with respect to transfusion independence, showed that autologous HBG1/2 promoter-modified CD34+ HSPCs gene therapy resulted in an adequate amount of HbF as early as 2 months after infusion led to near-normal hemoglobin levels, remained transfusion-free through the reported period without product related SAE. After RM-001 infusion, high levels of HbF proportion and on-target editing in bone marrow cells were maintained. Submitted on behalf of the RM-001 Investigators.

Keywords: thalassemian, genetherapy, CRISPR/Cas9, HbF

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Authors: Andrew Thayer, Courtney Rondeau, Paraskevi Papadopoulou

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The Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR) gene-editing technologies have generated considerable discussion about the applications and ethics of their use. However, no consistent guidelines for using CRISPR technologies have been developed -nor common legislation passed related to gene editing, especially as it is connected to genetically modified organisms (GMOs) in the European Union. The recent announcement that the first babies with CRISPR-edited genes were born, along with new studies exploring CRISPR’s applications in treating thalassemia, sickle-cell anemia, cancer, and certain forms of blindness, have demonstrated that the technology is developing faster than the policies needed to control it. Therefore, it can be seen that a reasonable and coherent regulatory framework for the use of CRISPR in human somatic and germline cells is necessary to ensure the ethical use of the technology in future years. The European Union serves as a unique region of interconnected countries without a standard set of regulations or legislation for CRISPR gene-editing. We posit that the EU would serve as a suitable model in comparing the legislations of its affiliated countries in order to understand the practicality and effectiveness of adopting majority-approved practices. Additionally, we present a proposed set of guidelines which could serve as a basis in developing a consistent regulatory framework for the EU countries to implement but also act as a good example for other countries to adhere to. Finally, an additional, multidimensional framework of smart solutions is proposed with which all stakeholders are engaged to become better-informed citizens.

Keywords: CRISPR, ethics, regulatory framework, European legislation

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Authors: Naser Shagerdi Esmaeli, Mohsen Hamidpour, Parisa Hasankhani Tehrani

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Background And Objective: Haematopoietic stem cell transplant is a potentially curative treatment option in various benign and malignant haematological diseases. Patients undergoing stem cell transplant procedure require blood transfusion on a daily basis. Currently, there is paucity of data from developing countries on transfusion practices. This audit was undertaken to determine the consumption of packed red blood cells (PRBCs) transfusion in the bone marrow transplant unit of the Shahid Ghazi Tabatabaei Hospital, Tabriz, Iran. Subjects And Methods: A retrospective audit was conducted for packed red cell transfusion ordering practice over a period from March 2017 to march 2018. All consecutive patients admitted for stem cell transplant procedure for various underlying diseases were included. Outcome measures used in this study were (i) cross match to transfusion (C: T) ratio and (ii) transfusion trigger. Results: During the study period, n=13 patients underwent a haematopoietic stem cell transplant. There were n=10 males and n=3 females. One patient was less than 15 years of age, while rests were adults. Median age±SD was 26.5±14.5 years (12∼54 years). The underlying diagnosis included Aplastic anemia (n=4), Thalassemia major (n=1), Multiple Myeloma (n=3), Acute leukemia (n=3), Hodgkin's lymphoma (n=1), PRCA (n=1). Grand total consumption of PRBCs during the study period was 204, while 258 products were crossmatch. The C:T ratio was 1.26. The transfusion trigger was Hb level of less than 8 gr/dl. Conclusion: The results of our BMT unit indicate that the C:T ratio and transfusion trigger is comparable to the international criteria and pioneer country in BMT transplantation. Also, we hope that our blood consumption become less than it is now.

Keywords: blood consumption, C: T ratio, PRBCs, stem cell transplant, tabriz, Iran

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Authors: Wafa Al Jabri

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Background: In Middle Eastern Islamic Countries (MEICs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern, especially with the increase in affected populations along with the associated psychological, social, and financial cost of management. Despite the availability of premarital screening services (PSS) that aim to identify the asymptomatic carriers of GBDs and provide genetic counseling to couples in order toreduce the prevalence of these diseases; yet, the success rate of PSS is very low due to religious and socio-cultural concerns. Purpose: This paper aims to highlight the factors that affect the success of PSS in MEICs. Methods: A literature review of articles located in CINAHL, PubMed, SCOPUS, and MedLinewas carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders.” Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MEICs countries and published in the last five years were included. Studies that were not published in English were excluded. Results: Fourteen articles were included in the review. The results showed that PSS in most of the MEICs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meetitsultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, religious beliefs, availability of prenatal diagnosis and therapeutic abortion, emotional factors, and availability of genetic counseling services. However, poor public awareness, late timing of the screening, and unavailability of adequate counseling services were the most common barriers identified. Conclusion: Overcoming the identified barriers by providing effective health education programs, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling would be crucial steps to provide a framework for an effective PSS in MEICs.

Keywords: premarital screening, success, effectiveness, and genetic blood disorders

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Authors: Lesley Northrop, Justin DeGrazia, Jessica Greenwood

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ASPIRA Labs now offers an en-suit and ready-to-implement technology transfer solution to enable labs and hospitals that lack the resources to build it themselves to offer in-house genetic testing. This unique platform employs a patented Molecular Inversion Probe (MIP) technology that combines the specificity of a hybrid capture protocol with the ease of an amplicon-based protocol and utilizes an advanced bioinformatics analysis pipeline based on machine learning. To demonstrate its efficacy, two independent genetic tests were validated on this technology transfer platform: expanded carrier screening (ECS) and hereditary cancer testing (HC). The analytical performance of ECS and HC was validated separately in a blinded manner for calling three different types of variants: SNVs, short indels (typically, <50 bp), and large indels/CNVs defined as multi-exonic del/dup events. The reference set was constructed using samples from Coriell Institute, an external clinical genetic testing laboratory, Maine Molecular Quality Controls Inc. (MMQCI), SeraCare and GIAB Consortium. Overall, the analytical performance showed a sensitivity and specificity of >99.4% for both ECS and HC in detecting SNVs. For indels, both tests reported specificity of 100%, and ECS demonstrated a sensitivity of 100%, whereas HC exhibited a sensitivity of 96.5%. The bioinformatics pipeline also correctly called all reference CNV events resulting in a sensitivity of 100% for both tests. No additional calls were made in the HC panel, leading to a perfect performance (specificity and F-measure of 100%). In the carrier panel, however, three additional positive calls were made outside the reference set. Two of these calls were confirmed using an orthogonal method and were re-classified as true positives leaving only one false positive. The pipeline also correctly identified all challenging carrier statuses, such as positive cases for spinal muscular atrophy and alpha-thalassemia, resulting in 100% sensitivity. After confirmation of additional positive calls via long-range PCR and MLPA, specificity for such cases was estimated at 99%. These performance metrics demonstrate that this tech-transfer solution can be confidently internalized by clinical labs and hospitals to offer mainstream ECS and HC as part of their test catalog, substantially increasing access to quality germline genetic testing for labs of all sizes and resources levels.

Keywords: clinical genetics, genetic testing, molecular genetics, technology transfer

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Authors: Wafa Al Jabri

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Background: In Middle Eastern Countries (MECs), there is a high prevalence of genetic blood disorders (GBDs), particularly sickle cell disease and thalassemia. The GBDs are considered a major public health concern that place a huge burden to individuals, families, communities, and health care systems. The high rates of consanguineous marriages, along with the unacceptable termination of at-risk pregnancy in MECs, reduce the possible solutions to control the high prevalence of GBDs. Since the early 1970s, most of MECs have started introducing premarital screening services (PSS) as a preventive measure to identify the asymptomatic carriers of GBDs and to provide genetic counseling to help couples plan for healthy families; yet, the success rate of PSS is very low. Purpose: This paper aims to highlight the factors that affect the success of PSS in MECs. Methods: An integrative review of articles located in CINAHL, PubMed, SCOPUS, and MedLine was carried out using the following terms: “premarital screening,” “success,” “effectiveness,” and “ genetic blood disorders”. Second, a hand search of the reference lists and Google searches were conducted to find studies that did not exist in the primary database searches. Only studies which are conducted in MECs and published after 2010 were included. Studies that were not published in English were excluded. Results: Eighteen articles were included in the review. The results showed that PSS in most of the MECs was successful in achieving its objective of identifying high-risk marriages; however, the service failed to meet its ultimate goal of reducing the prevalence of GBDs. Various factors seem to hinder the success of PSS, including poor public awareness, late timing of the screening, culture and social stigma, lack of prenatal diagnosis services and therapeutic abortion, emotional factors, religious beliefs, and lack of genetic counseling services. However, poor public awareness, late timing of the screening, religious misbeliefs, and the lack of adequate counseling services were the most common barriers identified. Conclusion and Implications: The review help in providing a framework for an effective preventive measure to reduce the prevalence of GBDs in MECS. This framework focuses primarily in overcoming the identified barriers by providing effective health education programs in collaboration with religious leaders, offering the screening test to young adults at an earlier stage, and tailoring the genetic counseling to consider people’s values, beliefs, and preferences.

Keywords: premarital screening, middle east, genetic blood disorders, factors

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