Performance Comparison Between Conventional Fluorescent Spot Test and Quantitative Assay in Detecting G6PD Deficiency in Neonates

Objectives: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is the most common enzymopathy worldwide. The fluorescent spot test (FST) is the conventional method for screening neonates for G6PD. However, it has limitations and quantitative assays such as the CareStart Biosensor 1 are being increasingly recommended. This study aimed to compare FST and CareStart Bioensor 1 in their ability to detect G6PD levels in neonates. Methods: This cross-sectional study involved 455 neonates between June and December 2020. Two milliliters of cord blood were analyzed with CareStart Biosensor 1 and dried cord blood spots with FST. Data was recorded and statistically analyzed. Sensitivity, specificity, positive predictive value, and negative predictive value were calculated to determine the performance of FST at specific G6PD cut-off values; Cohen’s kappa analysis assessed the agreement between the two methods. Results: The sensitivity of FST at 30% cut-off G6PD activity level was 91.0%, (95% CI: 57.0–100) and specificity of 97.0% (95% CI: 95.0–98.0). At 60% cut-off, the FST sensitivity sharply declined to 29.0% (95% CI: 19.0–40.0) with a specificity of 100% (95% CI: 98.0–100). The overall prevalence of G6PD deficiency was 5.1% as measured by FST and 17.8% by Biosensor 1 (p< 0.001). Conclusions: In this study, FST missed a significant proportion of cases of intermediate G6PD levels. FST also misclassified several G6PD intermediate individuals as normal, rendering them susceptible to oxidative stress. Biosensor 1 reported a significantly higher prevalence of G6PD deficiency

Blood transfusion knowledge among nurses in Malaysia:a university hospital experience

Blood transfusion is a fundamental and life-saving procedure where the consequence of errors can be fatal. Nurses’ knowledge plays an essential role in ensuring quality and safety in blood transfusion. The objective of this study was to assess blood transfusion-associated knowledge of tertiary hospital nurses on the east coast of Malaysia. This was a cross-sectional study with 200 registered nurses involved in blood transfusion procedures at Hospital Universiti Sains Malaysia. The knowledge of the nurses was evaluated by using the routine blood transfusion knowledge questionnaire based on five parts, and <50%, 50–74%, or ≥75% of the knowledge was considered as poor, moderate, or high, respectively. Based on the scoring system, the overall knowledge of blood transfusion among Malaysian nurses (33.2 ± 8.4 years) was estimated to be 54.9 ± 7.6%. In individual items, the scoring was 81.0%, 45.4%, 49.2%, 63.0%, and 90.0% in knowledge prior to blood transfusion, on pre-transfusion, on post-transfusion, on complications, and on transfusion policy, respectively. The findings of this study indicated that most of the nurses’ overall knowledge of blood transfusion was at a moderate level; therefore, training courses and continuous medical education are warranted to improve knowledge and skills of the nurses to ensure good practices of blood transfusion

Epigenetic insights and potential modifiers as therapeutic targets in β–thalassemia

Thalassemia, an inherited quantitative globin disorder, consists of two types, α– and β–thalassemia. β–thalassemia is a heterogeneous disease that can be asymptomatic, mild, or even severe. Considerable research has focused on investigating its underlying etiology. These studies found that DNA hypomethylation in the β–globin gene cluster is significantly related to fetal hemoglobin (HbF) elevation. Histone modification reactivates γ-globin gene expression in adults and increases β–globin expression. Down-regulation of γ–globin suppressor genes, i.e., BCL11A, KLF1, HBG-XMN1, HBS1L-MYB, and SOX6, elevates the HbF level. β–thalassemia severity is predictable through FLT1, ARG2, NOS2A, and MAP3K5 gene expression. NOS2A and MAP3K5 may predict the β–thalassemia patient’s response to hydroxyurea, a HbF-inducing drug. The transcription factors NRF2 and BACH1 work with antioxidant enzymes, i.e., PRDX1, PRDX2, TRX1, and SOD1, to protect erythrocytes from oxidative damage, thus increasing their lifespan. A single β–thalassemia-causing mutation can result in different phenotypes, and these are predictable by IGSF4 and LARP2 methylation as well as long non-coding RNA expression levels. Finally, the coinheritance of β–thalassemia with α–thalassemia ameliorates the β–thalassemia clinical presentation. In conclusion, the management of β–thalassemia is currently limited to genetic and epigenetic approaches, and numerous factors should be further explored in the future

Detection of anti-D and anti-G in a pregnant woman: a case report

Antibody identification in Rh-negative pregnant women is usually done to detect RhD alloimmunisation. The G antigen is part of the Rh blood group and is ubiquitous on most D-positive red cells. The detection of anti-G however is complicated. The objective of this case report is to highlight the importance of identifying anti G correctly especially in managing antenatal patients. We herein report a case of a 30-year-old pregnant woman, who was thought to have anti-D and anti-C on initial antibody identification, was subsequently found out to have anti-G and anti-D on further testing

The first Malay database toward the ethnic-specific target molecular variation

BACKGROUND:The Malaysian Node of the Human Variome Project (MyHVP) is one of the eighteen official Human Variome Project (HVP) country-specific nodes. Since its inception in 9(th) October 2010, MyHVP has attracted the significant number of Malaysian clinicians and researchers to participate and contribute their data to this project. MyHVP also act as the center of coordination for genotypic and phenotypic variation studies of the Malaysian population. A specialized database was developed to store and manage the data based on genetic variations which also associated with health and disease of Malaysian ethnic groups. This ethnic-specific database is called the Malaysian Node of the Human Variome Project database (MyHVPDb). FINDINGS:Currently, MyHVPDb provides only information about the genetic variations and mutations found in the Malays. In the near future, it will expand for the other Malaysian ethnics as well. The data sets are specified based on diseases or genetic mutation types which have three main subcategories: Single Nucleotide Polymorphism (SNP), Copy Number Variation (CNV) followed by the mutations which code for the common diseases among Malaysians. MyHVPDb has been open to the local researchers, academicians and students through the registration at the portal of MyHVP ( http://hvpmalaysia.kk.usm.my/mhgvc/index.php?id=register ). CONCLUSIONS:This database would be useful for clinicians and researchers who are interested in doing a study on genomics population and genetic diseases in order to obtain up-to-date and accurate information regarding the population-specific variations and also useful for those in countries with similar ethnic background

Next-Generation Sequencing (NGS) and Third-Generation Sequencing (TGS) for the Diagnosis of Thalassemia

Thalassemia is one of the most heterogeneous diseases, with more than a thousand mutation types recorded worldwide. Molecular diagnosis of thalassemia by conventional PCR-based DNA analysis is time- and resource-consuming owing to the phenotype variability, disease complexity, and molecular diagnostic test limitations. Moreover, genetic counseling must be backed-up by an extensive diagnosis of the thalassemia-causing phenotype and the possible genetic modifiers. Data coming from advanced molecular techniques such as targeted sequencing by next-generation sequencing (NGS) and third-generation sequencing (TGS) are more appropriate and valuable for DNA analysis of thalassemia. While NGS is superior at variant calling to TGS thanks to its lower error rates, the longer reads nature of the TGS permits haplotype-phasing that is superior for variant discovery on the homologous genes and CNV calling. The emergence of many cutting-edge machine learning-based bioinformatics tools has improved the accuracy of variant and CNV calling. Constant improvement of these sequencing and bioinformatics will enable precise thalassemia detections, especially for the CNV and the homologous HBA and HBG genes. In conclusion, laboratory transiting from conventional DNA analysis to NGS or TGS and following the guidelines towards a single assay will contribute to a better diagnostics approach of thalassemia

Next-Generation Sequencing (NGS) and Third-Generation Sequencing (TGS) for the Diagnosis of Thalassemia

Thalassemia is one of the most heterogeneous diseases, with more than a thousand mutation types recorded worldwide. Molecular diagnosis of thalassemia by conventional PCR-based DNA analysis is time- and resource-consuming owing to the phenotype variability, disease complexity, and molecular diagnostic test limitations. Moreover, genetic counseling must be backed-up by an extensive diagnosis of the thalassemia-causing phenotype and the possible genetic modifiers. Data coming from advanced molecular techniques such as targeted sequencing by next-generation sequencing (NGS) and third-generation sequencing (TGS) are more appropriate and valuable for DNA analysis of thalassemia. While NGS is superior at variant calling to TGS thanks to its lower error rates, the longer reads nature of the TGS permits haplotype-phasing that is superior for variant discovery on the homologous genes and CNV calling. The emergence of many cutting-edge machine learning-based bioinformatics tools has improved the accuracy of variant and CNV calling. Constant improvement of these sequencing and bioinformatics will enable precise thalassemia detections, especially for the CNV and the homologous HBA and HBG genes. In conclusion, laboratory transiting from conventional DNA analysis to NGS or TGS and following the guidelines towards a single assay will contribute to a better diagnostics approach of thalassemia

Global Globin Network Consensus Paper: Classification and Stratified Roadmaps for Improved Thalassaemia Care and Prevention in 32 Countries

The Global Globin Network (GGN) is a project-wide initiative of the Human Variome/Global Variome Project (HVP) focusing on haemoglobinopathies to build the capacity for genomic diagnosis, clinical services, and research in low- and middle-income countries. At present, there is no framework to evaluate the improvement of care, treatment, and prevention of thalassaemia and other haemoglobinopathies globally, despite thalassaemia being one of the most common monogenic diseases worldwide. Here, we propose a universally applicable system for evaluating and grouping countries based on qualitative indicators according to the quality of care, treatment, and prevention of haemoglobinopathies. We also apply this system to GGN countries as proof of principle. To this end, qualitative indicators were extracted from the IthaMaps database of the ITHANET portal, which allowed four groups of countries (A, B, C, and D) to be defined based on major qualitative indicators, supported by minor qualitative indicators for countries with limited resource settings and by the overall haemoglobinopathy carrier frequency for the target countries of immigration. The proposed rubrics and accumulative scores will help analyse the performance and improvement of care, treatment, and prevention of haemoglobinopathies in the GGN and beyond. Our proposed criteria complement future data collection from GGN countries to help monitor the quality of services for haemoglobinopathies, provide ongoing estimates for services and epidemiology in GGN countries, and note the contribution of the GGN to a local and global reduction of disease burden