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Hemoglobinopathies in neonates constitute a group of disorders influenced by genetic mutations in the human globin genes. They are often broadly categorized into quantitative defects or qualitative defects, though they are not mutually exclusive. In quantitative defects, the mutation causes insufficient production of a normal globin chain, which can range from no production to mild deficiency. These are typically referred to as thalassemias. In qualitative defects, the structure of the hemoglobin is altered. The most common structural hemoglobinopathy is sickle cell disease. During fetal development, distinct globin chains are synthesized, which undergo a progressive switch to adult globin chains perinatally. This affects the timing of the clinical presentation of these disorders and thus, our ability to diagnose them. In this review, we focus on the epidemiology, genetic causes, clinical presentation, and general overview and management of common hemoglobin disorders that may be encountered in the neonatal period., (Copyright © 2024 by the American Academy of Pediatrics.)

Background: Haemoglobinopathy refers to a group of common monogenic inherited conditions associated with variations in the haemoglobin molecule; however, there is relatively limited reporting on abnormal haemoglobinopathy in the Chinese population, especially rare abnormal haemoglobin (Hb). The aim of this study was to explore the clinical characteristics of haemoglobinopathy to supplement data for the epidemiological investigation of Hb variants in Guangdong province of China., Methods: Peripheral blood was collected from five patients (including a family) for Complete blood count, Hb electrophoresis, High-performance liquid chromatography analysis and degenerative globin body testing. Hb variants were further analysed by PCR and DNA sequencing., Results: The research subjects were diagnosed with different types of abnormal Hb. The blood routine of the Hb Fukuyama (HBB:c.232C>T) diagnosed individual showed microcytic hypochromic anaemia, with a lower Hb level (64 g/L), mean corpuscular volume (MCV) of 71.5 fL and mean corpuscular haemoglobin (MCH) of 21.5 pg. Individuals diagnosed with Hb Port Phillip (HBA2:c.275T>C) exhibit a MCH level that is slightly below average, at 26.4 pg. The Hb Saint Etienne (HBB:c.279C>G) diagnosed individual showed macrocytic hypochromic anaemia, and the proband had a low Hb level (116 g/L), MCV of 102.2 fL and MCH of 29.4 pg., Conclusion: We confirmed the presence of Hb Fukuyama (HBB:c.232C>T) in China for the first time. Three rare patients with the Hb Saint Etienne (HBB:c.279C>G) phenotype and one patient with Hb Port Phillip (HBA2:c.275T>C) phenotype were included. Our research enriches the gene mutation map of haemoglobinopathy in Guangdong province and improves the detection system of haemoglobinopathy for population prevention and eugenics., (© 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.)

Background: Hemoglobinopathies are among the most prevalent inherited disorders globally, with carrier prevalence varying significantly across regions. In Saudi Arabia, high rates of consanguineous marriages amplify the risk of these disorders., Aim: This study aims to assess the burden of hemoglobinopathies by evaluating the prevalence and regional distribution of beta-hemoglobin variants, including rare variants, among couples participating in the national premarital screening program., Methods: Data were collected from the premarital genetic screening program and entered into the SEHA platform, covering the 13 administrative regions of Saudi Arabia. Blood samples underwent various screening tests for infectious and genetic diseases. Hemoglobin electrophoresis samples were analyzed using capillary electrophoresis, High-Performance Liquid Chromatography (HPLC), or a combination of both methods., Results: From 2011 to 2018, 1,871,184 individuals were included in the study, with 49.8% male and 50.2% female. The average age was 30.2 years. Hemoglobin S (HbS) was identified in 88,431 individuals (4.7% of the tested population and 78.5% of abnormal screening results), primarily as a sickle cell trait. β-thalassemia was the second most common disorder, identified in 22,420 individuals (1.2% of the population and 19.9% of hemoglobin disorders). HbC and HbD were each detected in 0.04% of cases, while HbO-Arab was identified in 0.007% and HbG in 0.006%. Hemoglobin E and hemoglobin Lepore were found to be extremely rare., Conclusion: The study demonstrates regional variation in the prevalence of hemoglobin genetic variants in Saudi Arabia. To effectively mitigate this risk, it is imperative to strengthen public education and awareness, particularly focusing on genetic screening and counseling., (© 2024. The Author(s).)

Hemoglobin (Hb) disorders are among the most prevalent inherited diseases. Despite a limited number of involved genes, these conditions represent a broad clinical and prognostic spectrum. The menu of laboratory tests is extensive. From widely available modalities, for example, complete blood count to rather sophisticated molecular technologies, the investigation of Hb disorders recapitulates an increasing complexity of laboratory workup in other medical fields. This review highlights a current state of biochemical and molecular investigation of Hb disorders and offers a glimpse on technologies that are yet to be fully embraced in clinical practice., Competing Interests: Disclosure The authors have nothing to disclose., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: This study aimed to determine the prevalence of total blood cell abnormalities, hemoglobinopathies and G6PD deficiency and evaluate the efficacy of red blood cell (RBC) indices, mentzer index (MI) and naked-eye single tube red cell osmotic fragility (NESTROF) test as screening tools for diagnosis of β thalassemia trait among Yemeni blood donors., Methods: A cross-sectional study was conducted with 106 volunteer blood donors who met the national standard criterion of blood donation. Various tests were performed, including complete blood count (CBC), serum ferritin, sickling test, G6PD assay, NESTROF test and high-performance liquid chromatography (HPLC)., Results: The prevalence of hematological abnormalities among blood donors reached 68.9%, with functional RBC abnormalities at 51.9%, leukopenia at 10.4%, thrombocytosis at 1.9%, and thrombocytopenia at 4.7%. Additionally, hemoglobinopathies were found in 21.7% of donors, with β-thalassemia trait at 3.8%, sickle cell trait at 1.9%, and suspected α-thalassemia trait at 16%, while G6PD deficiency and iron deficiency were present in 12.3% and 17.9% of donors, respectively. The NESTROF test, MCV and MCH demonstrated a sensitivity rate of 100%. MI and MCH exhibited the highest specificity followed by NESTROF test in the screening of β-thalassemia trait., Conclusions: The prevalence of hemoglobinopathies and G6PD deficiency appear to be common among Yemeni blood donors. These results emphasize the necessity of comprehensive blood donation screening programs to safeguard the blood supply and promote early detection and management of hemoglobinopathies and G6PD deficiency in Yemen.

Background: Inherited hemoglobin disorders are common in clinical practice. While qualitative (i.e. sickle cell disease) and quantitative (thalassemia) hemoglobinopathies are usually diagnosed clinically and confirmed through simple laboratory assessments, hemoglobin variants with altered oxygen affinity often go undetected due to their typically silent clinical presentation. Hemoglobin (Hb) J-Auckland, a low oxygen affinity hemoglobin variant first described in 1987 in Auckland, New Zealand, is one such silent disorder., Case Presentation: We report for the first time a clinically evident case of previously undiagnosed Hb J-Auckland in an 8-year-old girl who presented with unexplained hypoxemia at high altitude. Her oxygen level was corrected with supplemental oxygen and when assessed at low altitude. A brief discussion of the diagnostic approach and clinical implications is provided., Conclusion: Standard hemoglobin analysis is essential for the evaluation of suspected altered affinity hemoglobinopathy, and genetic testing is often required for definitive diagnosis. Early recognition and diagnosis of these variants can prevent mismanagement and improve patient outcomes.

Introduction: Thalassemia and haemoglobinopathies are relatively common among Malaysians. One of the rare haemoglobinopathies reported is Haemoglobin (Hb) Arya, which occurs due to substitution of aspartic acid at residue 47 of the alpha chain by asparagine. Here, we report the detection of Hb Arya in a Malaysian family, which was detected incidentally during family screening., Case Report: A 16 years-old girl, clinically asymptomatic was noted to have low mean corpuscular haemoglobin (MCV) with normal Hb level. Hb analysis using capillary electrophoresis (CE) showed reduced Hb A of 76.5%, Hb A2 of 1.6% with presence of small peak at Zone 1 likely A2'. There was also a small peak noted at Hb D zone and Hb S zones which quantified as 1.5% and 20% respectively. Supplementary test by high performance liquid chromatography (HPLC) showed a prominent peak at D-window (19.6%) and a small peak at S-window (0.6%). DNA analysis revealed a heterozygous state of α2 codon 47 Hb Arya mutation. Subsequent family study showed a similar mutation in the father and sister of the index case., Conclusion: Very few reports are available up to date regarding Hb Arya. This report highlights the rare haemoglobinopathy in a Malay family in Malaysia that contributes to the growing literature of this rare haemoglobin variant.

Background: Hemoglobinopathies, the most common inherited blood disorder, are frequently underdiagnosed. Early identification of carriers is important for genetic counseling of couples at risk. The aim of this study was to develop and validate a novel machine learning model on a multicenter data set, covering a wide spectrum of hemoglobinopathies based on routine complete blood count (CBC) testing., Methods: Hemoglobinopathy test results from 10 322 adults were extracted retrospectively from 8 Dutch laboratories. eXtreme Gradient Boosting (XGB) and logistic regression models were developed to differentiate negative from positive hemoglobinopathy cases, using 7 routine CBC parameters. External validation was conducted on a data set from an independent Dutch laboratory, with an additional external validation on a Spanish data set (n = 2629) specifically for differentiating thalassemia from iron deficiency anemia (IDA)., Results: The XGB and logistic regression models achieved an area under the receiver operating characteristic (AUROC) of 0.88 and 0.84, respectively, in distinguishing negative from positive hemoglobinopathy cases in the independent external validation set. Subclass analysis showed that the XGB model reached an AUROC of 0.97 for β-thalassemia, 0.98 for α0-thalassemia, 0.95 for homozygous α+-thalassemia, 0.78 for heterozygous α+-thalassemia, and 0.94 for the structural hemoglobin variants Hemoglobin C, Hemoglobin D, Hemoglobin E. Both models attained AUROCs of 0.95 in differentiating IDA from thalassemia., Conclusions: Both the XGB and logistic regression model demonstrate high accuracy in predicting a broad range of hemoglobinopathies and are effective in differentiating hemoglobinopathies from IDA. Integration of these models into the laboratory information system facilitates automated hemoglobinopathy detection using routine CBC parameters., (© Association for Diagnostics & Laboratory Medicine 2024. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

REHem-AR was created in 2013. The progressive implementation of neonatal screening for haemoglobinopathies in Spanish autonomous communities where the registry had not been implemented, as well as the addition of new centres during this period, has considerably increased the sample of patients covered. In this study, we update our previous publication in this area, after a follow-up of more than 5 years. An observational, descriptive, multicentre and ambispective study of adult and paediatric patients with haemoglobinopathies and rare anaemias registered in REHem was performed. The data are from a cross-sectional analysis performed on 1 June, 2023. The study population comprised 1,756 patients, of whom 1,317 had SCD, 214 had thalassaemia and 224 were diagnosed with another condition. Slightly more than one third of SCD patients (37%) were diagnosed based on neonatal bloodspot screening, and the mean age at diagnosis was 2.5 years; 71% of thalassaemia patients were diagnosed based on the presence of anaemia. Vaso-occlusive crisis and acute chest syndrome continue to be the most frequent complications in SCD. HSCT was performed in 83 patients with SCD and in 50 patients with thalassaemia. Since the previous publication, REHem-AR has grown in size by more than 500 cases. SCD and TM are less frequent in Spain than in other European countries, although the data show that rare anaemias are frequent within rare diseases. REHem-AR constitutes an important structure for following the natural history of rare anaemias and enables us to calculate investment needs for current and future treatments., (© 2024. The Author(s).)

Sickle cell diseases, β-thalassemia, and other hemoglobinopathies are common in Africa. Their distribution differs from one region to another. There are higher frequencies in Western and Northern Africa. Their clinical complications presented a real public health problem in each country. For this, early treatment can improve the severity of these diseases. Hemoglobinopathies targeted by screening are associated with SCD, β, and α thalassemia. Our study aim is to report our experience with newborn screening for hemoglobinopathy in Tunis. The 156 newborn's cord blood was collected at the time of childbirth in the center region (Farhat Hached Hôspital). We opted for hemoglobin exploration to achieve maximum efficiency and effectiveness in screening. After that, all patients suspected to have hemoglobinopathies are affected by molecular investigation. Our findings showed the presence of some hemoglobinopathies such as β-thalassemia and α-thalassemia with the following frequencies: 12% and 0.33%. The molecular results show the presence of HBB: c.93-21G>A, IVS-I-110G>A, HBBc. -106G>A -56G>C, HBBc.404T>C, Hb Yaounde described for the first time in Tunisia and α 3,7 . In conclusion, newborn screening diagnoses neonates with different examples of hemoglobinopathies, which will be beneficial not only for the care of the child but also for genetic counseling of the potential risk's parents., Competing Interests: The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Aims: The importance of screening for hemoglobinopathies is well-documented in India. However, information on the distribution of hemoglobinopathies in Karnataka is lacking. The present study focuses on determining the spectrum of hemoglobinopathies for various districts of Karnataka., Materials and Methods and Results: A retrospective analysis of samples registered for hemoglobinopathies for a period of 5 years (2017-2021) was carried out. A total of 17066 records registered only from the Karnataka region, were anonymized and retrieved. The data included gender, age, district, and results of the tests. The results were based on complete blood count, peripheral smear, and capillary electrophoresis (CE) pattern. The data were revalidated by pathologists, and the unambiguous data were analyzed for the study. One-fourth of the records (25%) showed abnormal hematological parameters. The number of female records (66%) was twice that of males and both genders showed higher distribution of thalassemia, followed by variants and double heterozygotes (DH). Several cases of thalassemia major were identified below the age of 17 years. The majority of thalassemia cases were β thal and 93% of them were β thal trait. Among the variants, HbS was more prevalent than HbE. Among the districts, Hassan had a 35.2% thal, Mysuru had a 7.2% variant, and Chitradurga had a 5.5% DH. Thalassemia, variants, and DH were distributed across several districts of Karnataka to various levels., Conclusion: The comprehensive retrospective analysis of the spectrum of hemoglobinopathies in various districts of Karnataka serves as evidence to carry out a prospective study on population screening where the incidence of thalassemia and structural variants is high., (Copyright © 2023 Copyright: © 2023 Indian Journal of Pathology and Microbiology.)

Haemoglobin disorders represent a heterogeneous group of inherited conditions that involve at least one genetic abnormality in one or more of the globin chains, resulting in changes in the structure, function, and/or amount of haemoglobin molecules, which are very important for their related clinical aspects. Detecting and characterizing these disorders depends primarily on laboratory methods that employ traditional approaches and, when necessary, newer methodologies essential for solving a number of diagnostic challenges. This review provides an overview of key laboratory techniques in the diagnosis of haemoglobinopathies, focusing on the challenges, advancements, and future directions in this field. Moreover, many haemoglobinopathies are benign and clinically silent, but it is not uncommon to find unexpected variants during routine laboratory tests. The present work reported a rare and clinically interesting case of identification of haemoglobin fractions in an adult man by the determination of glycated haemoglobin (HbA 1c ) during a routine laboratory assessment, highlighting how the correct use of laboratory data can modify and improve the patient's clinical management.

Aim: To develop a non-invasive prenatal test for beta-hemoglobinopathies based on analyzing maternal plasma by using next generation sequencing., Methods: We applied next generation sequencing (NGS) of maternal plasma to the non-invasive prenatal testing (NIPT) of autosomal recessive diseases, sickle cell disease and beta-thalassemia. Using the Illumina MiSeq, we sequenced plasma libraries obtained via a Twist Bioscience probe capture panel covering 4 Kb of chromosome 11, including the beta-globin (HBB) gene and >450 genomic single-nucleotide polymorphisms (SNPs) used to estimate the fetal fraction (FF). The FF is estimated by counting paternally transmitted allelic sequence reads present in the plasma but absent in the mother. We inferred fetal beta-globin genotypes by comparing the observed mutation (Mut) and reference (Ref) read ratios to those expected for the three possible fetal genotypes (Mut/Mut; Mut/Ref; Ref/Ref), based on the FF., Results: We bioinformatically enriched the FF by excluding reads over a specified length via in-silico size selection (ISS), favoring the shorter fetal reads, which increased fetal genotype prediction accuracy. Finally, we determined the parental HBB haplotypes, which allowed us to use the read ratios observed at linked SNPs to help predict the fetal genotype at the mutation site(s). We determined HBB haplotypes via Oxford Nanopore MinION sequencing of a 2.2 kb amplicon and aligned these sequences using Soft Genetics' NextGENe LR software., Conclusion: The combined use of ISS and HBB haplotypes enabled us to correctly predict fetal genotypes in cases where the prediction based on variant read ratios alone was incorrect.

The hemoglobin (Hb) variants are qualitative abnormalities due to production of structurally abnormal globin proteins. They are categorized based on the type of mutation present in the α1, α2, β, Gγ, Aγ and δ globin genes. So far, more than 1550 Hb variants are reported in the database. They could lead to Hb polymerization, Hb instability, altered oxygen affinity and decreased oxygen-carrying capacity of Hb or have no clinical manifestations. In India, ethnic diversity, consanguinity, regional variations and migration result in the presence of different Hb variants. We have compiled all the variants of α, β and δ globin chains in heterozygous, homozygous and in compound heterozygous forms reported from India in the last 52 years. Of the 63 rare and novel hemoglobin variants reported from India, 22 were α-globin chain variants, 37 were β-globin chain variants and 4 were δ-globin chain variants. Twelve novel Hb variants (Hb J Rajappan, Hb Koya Dora, Hb Rampa, Hb Godavari, Hb Chandigarh, Hb D Agri, Hb Lucknow, Hb Vellore, Hb Midnapore, Hb Bijnor, Hb A 2 Tianhe and Hb A 2 Saurashtra) were identified among persons of Indian origin. Majority of them were picked up on HPLC. Some of the variants like Hb Titusville, Hb Shimonoseki, Hb Chandigarh, Hb D Agri, Hb Yaizu and Hb Vellore eluted in the HbS window whereas variants like HbD Iran, Hb St. Louis, Hb G Coushata, HbM Saskatoon, Hb Lucknow, Hb Grange-Blanche and Hb Tianshui showed falsely elevated HbA 2 . Hence, careful and systematic investigations are required to identify them., (© 2024 John Wiley & Sons Ltd.)

We report a new low-affinity hemoglobinopathy (Hemoglobin Oviedo) in a family with isolated low oxygen saturation (89-92%) caused by a previously undescribed variant (NM_000518.5: c.115A > G;p.Thr39Ala) in the hemoglobin subunit β encoding gene ( HBB gene) located on chromosome 11.

Objective: In this study, we report a Tunisian newborn boy referred for neonatal hemolytic anemia with yellowish skin and enlarged spleen due to coinheritance of hemoglobin O (HbO) Arab and β-thalassemia., Study Design: Hematological parameters were collected using an automated blood cell counter. The amounts of Hb fractions were measured by capillary electrophoresis of Hb. Amplification and sequencing of the HBB gene were performed by Sanger's method., Results: Family study and genetic analysis revealed that the proband was a carrier of two hemoglobinopathies: HbO Arab and β 0 -thalassemia., Conclusion: The coexistence of these two pathologies complicated the general state of the newborn boy and led to a severe anemia at birth., Key Points: · Severe neonatal anemia can be caused by hemoglobinopathy.. · Coinheritance of HbO Arab/β0-thalassemia complicated the general state of the newborn.. · Diagnosing hemoglobinopathy at an early age improves patient care.., Competing Interests: None declared., (Thieme. All rights reserved.)

Introduction. The first neonatal screening program in Colombia – PREGEN – was set up in the medical private sector of Bogotá in 1988. We report the results from recent years that, given the scarcity of similar information in our country, may help estimate the frequency of the evaluated neonatal disorders and which ones should be included in the neonatal screening programs in our country. Objective. To describe the results of PREGEN´s newborn screening program between 2006 and 2019. Materials and methods. We analyzed databases and other informative documents preserved in PREGEN from the 2006-2019 period. Results. One in every 164 newborns screened in our program had an abnormal hemoglobin variant, and one in every 194 carried some hemoglobin S variant. Glucose-6- phosphate dehydrogenase deficiency and congenital hypothyroidism are next as the more common disorders. Conclusions. Abnormal hemoglobin causes the most frequent monogenic disorder in the world. Glucose-6-phosphate dehydrogenase deficiency is the most common enzymopathy affecting nearly 400 million individuals worldwide. Since both disorders are more common in people of African descent and confer some resistance to malaria, we believe that screening for both disorders may be more relevant in the areas with African ancestry in our country.

In this report, we describe a 6-year-old girl with a medical history of pallor, mild icterus, anemia, blood transfusion and abnormal hemoglobin variant analysis on capillary electrophoresis. She was referred for further analysis. DNA sequencing of the proband revealed a de novo mutation in Codon 88 (CTG > CCG) of the β-globin gene ( HBB : c.266T > C) in a heterozygous state compatible with hemoglobin Santa Ana, an unstable hemoglobin. This is the first case of Hb Santa Ana from Iran associated with moderate to severe anemia who underwent splenectomy with clinical improvement.

Hemoglobin (Hb) disorders are among the most common monogenic diseases affecting nearly 7% of the world population. Among various Hb disorders, approximately 1.5% of the world population carries β -thalassemia ( β -Thal), affecting 40,000 newborns every year. Early screening and a timely diagnosis are essential for β -thalassemia patients for the prevention and management of later clinical complications. However, in Africa, Southern Europe, the Middle East, and Southeast Asia, where β -thalassemia is most prevalent, the diagnosis and screening for β -thalassemia are still challenging due to the cost and logistical burden of laboratory diagnostic tests. Here, we present Gazelle, which is a paper-based microchip electrophoresis platform that enables the first point-of-care diagnostic test for β -thalassemia. We evaluated the accuracy of Gazelle for the β -Thal screening across 372 subjects in the age range of 4-63 years at Apple Diagnostics lab in Mumbai, India. Additionally, 30 blood samples were prepared to mimic β -Thal intermediate and β -Thal major samples. Gazelle-detected levels of Hb A, Hb F, and Hb A 2 demonstrated high levels of correlation with the results reported through laboratory gold standard high-performance liquid chromatography (HPLC), yielding a Pearson correlation coefficient = 0.99. This ability to obtain rapid and accurate results suggests that Gazelle may be suitable for the large-scale screening and diagnosis of β -Thal.

Objectives: Hemoglobinopathies, including thalassemia and hemoglobin (Hb) variants, are common hematological disorders in tropical countries. Accurate and precise separation of hemoglobin types and reliable quantitation are necessary for differential diagnosis of these disorders., Methods: We have evaluated the analytical performances of premier resolution-high-performance liquid chromatography (PR-HPLC; Trinity Biotech, Co. Wicklow, Ireland) to assist in the presumptive diagnosis of thalassemia and Hb variants commonly found in Southeast Asian countries. HbA 0 , HbA 2 , HbE, and HbF levels were separated and quantified in 120 blood samples from unrelated adult subjects and compared with those analyzed by capillary zone electrophoresis (CZE; CAPILLARYS™ 2, Sebia, Norcross, GA, US). The Hb analysis patterns of Hb variants obtained from the PR-HPLC system were also compared to those obtained from HPLC (VARIANT II, β-thalassemia Short Program, Bio-Rad, Laboratories, Hercules, CA, US) and CZE systems., Results: The PR-HPLC had excellent precision with a coefficient of variation (CV) for HbA 2 quantitation of 3.8 % within-run and 5.2 % between-run. The levels of HbA 2 /E quantified by the PR-HPLC system correlated well with those of the CZE system ( r =0.997). In addition, thalassemia interpretation results obtained from the PR-HPLC and the CZE showed 100 % agreement. Moreover, chromatograms of the PR-HPLC were also comparable to those of VII-HPLC and CAP2-CZE electropherograms., Conclusions: The PR-HPLC system would be applicable to diagnose common forms of thalassemia and Hb variants in Southeast Asia., (© 2024 Walter de Gruyter GmbH, Berlin/Boston.)

Thalassemia major is one of the health problems in Iraq, especially in Kurdistan. Pre-marriage mandatory preventive screening program was established in Kurdistan in 2008, which allowed us to study the prevalence of different hemoglobinopathies among newly married young adults in this region. A total of 1154 subjects (577 couples) attending the Koya district, premarital Health center, were screened using red cell indices. Those who had mean corpuscular volume (MCV)<80 fl and mean corpuscular hemoglobin (MCH)<27 pg had high-performance liquid chromatography and iron studies. Out of 1154 individuals that were evaluated, 183 (11.9%) had low MCV and MCH. Of the former 183 subjects, 69 (5.97%) had β-thalassemia trait, 10 (0.86%) had δβ-thalassemia trait, and no other hemoglobinopathies were recorded in our study. There was second-degree consanguinity in 4.7% of all 577 couples. In two couples, both partners had β-thalassemia trait and both were consanguineous. Both couples decided to separate after counseling. Based on the current study, the role of the premarital screening program in decreasing the number of new thalassemia major cases among the Kurdish population is laudable. Therefore, mandatory premarital screening is advised in all parts of Iraq.

Unstable variant hemoglobinopathies are an uncommon cause of hemolysis in the pediatric patient and may cause a delay in diagnosis if there is not a high index of suspicion. Hemoglobin (Hb) Mizuho is a rare unstable hemoglobinopathy caused by a pathogenic variant of the HBB gene with a severe phenotype. Here we report on the first known case of Hb Mizuho in Australia, presenting with features of acute and chronic hemolysis. The morphological features on blood film review, in conjunction with biochemical findings and other clinical features, did not immediately suggest an alternative diagnosis and a Next Generation Sequencing gene analysis approach was taken to investigate genes associated with red blood cell disorders and atypical uremic syndrome. The HBB Mizuho variant was detected and established the diagnosis. This report highlights the challenge of diagnosing Hb Mizuho on conventional testing and the need for early genomic testing to clarify a diagnosis.

Accurate laboratory screening for sickle cell disease and other haemoglobin disorders is expanding worldwide. Two new reports describe different methods and strategies for screening in Mali and Denmark, respectively, and their encouraging results suggest that countries should tailor their screening programmes according to local needs, resources and opportunities. Commentary on: Guindo et al. Potential for a large-scale newborn screening strategy for sickle cell disease in Mali: a comparative diagnostic performance study of two rapid diagnostic tests (SickleScan® and HemotypeSC®) on cord blood. Br J Haematol 2024;204:337-345 and Gravholt et al. The Danish national haemoglobinopathy screening programme: report from 16 years of screening in a low-prevalence, non-endemic region. Br J Haematol 2024;204:329-336., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

Introduction: Beta thalassemia and hemoglobin (HbE)-related hemoglobinopathies are common public health problems in developing countries. High-performance liquid chromatography (HPLC) is currently the diagnostic test of choice for carrier detection, but it is costly. Hence, some initial screening and complementary tests are required, which can be affordable., Aims: To find out the distribution of different red blood cell (RBC) indices in beta thalassemia trait (BTT) and HbE-related hemoglobinopathies and to determine their significance as screening tests to distinguish between these hemoglobinopathies., Study Settings and Design: This observational cross-sectional study has been carried out at an NABL (National Accreditation Board for Testing and Calibration Laboratories)-accredited Laboratory of Eastern India with approval from the concerned Institutional Ethics Committee from January 2021 to March 2021., Methods and Material: : HPLC tests and complete hemograms were performed on 2247 ethylenediaminetetraacetic acid anti-coagulated blood samples over 3 months. Patients <1 year of age or having a history of blood transfusion within the past 06 months were excluded., Statistical Analysis: : One-way analysis of variance along with Bonferroni post-hoc test was performed to find out significant differences of means of mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), hemoglobin%, red blood cell (RBC) count, and red cell distribution width (RDW-CV) among concerned hemoglobinopathies., Results: The results show a significant difference of total RBC count, RDW, MCV, MCH, and MCHC between BTT and E-trait. No significant difference of mean was found between HbE homozygous and E-beta. E-trait differs from both HbE homozygous and E-beta significantly in three parameters, namely, RDW, MCV and MCH. A value of MCV at ≤73.8 fl and MCH at ≤21.9 pg may be a clue of diagnosis for BTT rather than E-trait with >90% sensitivity and >80% specificity., Conclusion: RBC indices vary significantly between BTT and other HbE-related hemoglobinopathies. They can specially be utilized to differentiate BTT and E-trait as supportive tests in addition to the gold standard test of HPLC.

The Danish national haemoglobinopathy screening programme seeks to determine parental haemoglobinopathy carrier state antenatally. In this retrospective register-based study, we evaluated the 16-year trajectory of this programme, utilising the Danish Red Blood Cell Centre's laboratory database, covering approximately 77% of the Danish population. During the study period, we observed a substantial increase in annual diagnostic examinations performed, from 389 in 2007 to 3030 in 2022. Women constituted 88% of these cases, aligning with the emphasis of the screening programme. Of these, 54% of women of reproductive age (15-40 years) and 10% of women >40 years were specified as pregnant. During our study period, 61 children were born with a severe haemoglobinopathy, out of which 23 children were born from mothers not residing in Denmark during their first trimester thus not included in the screening programme. Prenatal invasive testing was performed for 60 fetuses, identifying 12 with homozygous or compound heterozygous haemoglobinopathy. The Danish haemoglobinopathy screening programme has provided screening, information and reproductive choices for numerous families. During the study period, screening for haemoglobinopathies has been steadily increasing and is expected to continue to increase. Awareness of and adherence to the screening programme is subject of further investigation and optimisation., (© 2023 The Authors. British Journal of Haematology published by British Society for Haematology and John Wiley & Sons Ltd.)

For this paper, cases reported formally and anecdotally to the authors in their screening and diagnostic roles have been selected to demonstrate areas where errors have occurred, and caution should be exercised. The cases demonstrate that it is vital that the performance and limitations of the techniques used, along with the phenotypic presentation of cases where haemoglobin variants and/or thalassaemias are coinherited are understood by those performing result interpretation. Those who deliver the service as well as those who receive reports and give results and counselling should be aware of the complexity of the topic., (© 2023 British Society for Haematology and John Wiley & Sons Ltd.)

The genetic regulation of hemoglobin is complex and there are a number of genetic abnormalities that result in clinically important hemoglobin disorders. Here, we review the molecular pathophysiology of hemoglobin disorders and review both old and new methods of diagnosing these disorders. Timely diagnosis of hemoglobinopathies in infants is essential to coordinate optimal life-saving interventions, and accurate identification of carriers of deleterious mutations allows for genetic counseling and informed family planning. The initial laboratory workup of inherited disorders of hemoglobin should include a complete blood count (CBC) and peripheral blood smear, followed by carefully selected tests based on clinical suspicion and available methodology. We discuss the utility and limitations of the various methodologies to fractionate hemoglobin, including cellulose acetate and citrate agar hemoglobin electrophoresis, isoelectric focusing, high-resolution high-performance liquid chromatography, and capillary zone electrophoresis. Recognizing that most of the global burden of hemoglobin disorders exists in low- and middle-income countries, we review the increasingly available array of point-of-care-tests (POCT), which have an increasingly important role in expanding early diagnosis programs to address the global burden of sickle cell disease, including Sickle SCAN, HemoTypeSC, Gazelle Hb Variant, and Smart LifeLC. A comprehensive understanding of the molecular pathophysiology of hemoglobin and the globin genes, as well as a clear understanding of the utility and limitations of currently available diagnostic tests, is essential in reducing global disease burden., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Hemoglobin (Hb) abnormalities, such as thalassemia and structural Hb variants, are among the most prevalent inherited diseases and are associated with significant mortality and morbidity worldwide. However, there were not comprehensive reviews focusing on different clinical analytical techniques, research methods and artificial intelligence (AI) used in clinical screening and research on hemoglobinopathies. Hence the review offers a comprehensive summary of recent advancements and breakthroughs in the detection of aberrant Hbs, research methods and AI uses as well as the present restrictions anddifficulties in hemoglobinopathies. Recent advances in cation exchange high performance liquid chromatography (HPLC), capillary zone electrophoresis (CZE), isoelectric focusing (IEF), flow cytometry, mass spectrometry (MS) and polymerase chain reaction (PCR) etc have allowed for the definitive detection by using advanced AIand portable point of care tests (POCT) integrating with smartphone microscopic classification, machine learning (ML) model, complete blood counts (CBC), imaging-based method, speedy immunoassay, and electrochemical-, microfluidic- and sensing-related platforms. In addition, to confirm and validate unidentified and novel Hbs, highly specialized genetic based techniques like PCR, reverse transcribed (RT)-PCR, DNA microarray, sequencing of genomic DNA, and sequencing of RT-PCR amplified globin cDNA of the gene of interest have been used. Hence, adequate utilization and improvement of available diagnostic and screening technologies are important for the control and management of hemoglobinopathies., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

Objective: The capillary zone electrophoresis (CZE) and high-performance liquid chromatography (HPLC) methods were compared in terms of HbA2 measurement for the assessment of hemoglobinopathies., Materials and Methods: CZE was compared with HPLC for the evaluation of patients without hemoglobinopathy (n=321), with β-thalassemia trait (n=113), and with common (HbD-Punjab, E, C, S/A, and S/S) and rare (HbS/D, O-Arap, Lepore, G-Coushata, Setif, Hamadan, Q-Iran, and H) variants (n=21). The reference range for HbA2 was determined by CZE., Results: Among patients without hemoglobinopathy, the median (2.5 th -97.5 th percentiles) values were 97.4% (97.0-98.0%) and 97.5% (96.6-98.4%) for HbA (p=0.060) and 2.4% (1.6-3.0%) and 2.5% (1.6-3.1%) for HbA2 (p<0.001) by HPLC and CZE, respectively. The reference range for HbA2 was 1.6-3.1% by CZE. In the comparison of methods for HbA2, there was a constant error of 0.255 (confidence interval: 0.062-0.448) and bias of 0.10% (limit of agreement: 0.33-0.53), and higher values were obtained with CZE. A strong correlation was observed between the methods (r=0.782). Interrater agreement was almost perfect for clinical diagnosis (ϰ=0.911). The two methods detected and identified the common variants similarly. All rare variants, except HbH by HPLC and HbS/D by CZE, were detected as separate peaks by both methods., Conclusion: The two methods were in agreement regarding the preliminary identification of β-thalassemia patients. Different Hb variants were detected by both methods but with possible methodological interference for HbA2 measurements. CZE is a reliable and simple alternative for the evaluation of hemoglobinopathies. The standardization of HbA2 measurements should be prioritized as more techniques become available in routine laboratory practice., Competing Interests: Conflict of Interest: No conflict of interest was declared by the authors., (©Copyright 2023 by Turkish Society of Hematology Turkish Journal of Hematology, Published by Galenos Publishing House.)

Haemoglobinopathies are among the most common inherited disorders around the world. In the United States the diagnosis of haemoglobinopathy or a carrier state is made by universal newborn screening. However, many individuals of childbearing age do not know they are a haemoglobinopathy carrier. Screening for common haemoglobinopathies is generally offered as a part of pregnancy planning so that prospective parents can be counselled regarding the risk of having a child with a haemoglobinopathy. Multiple tests exist to screen patients for presence of haemoglobinopathy carrier or disease state; however, it is crucial to order and interpret the results correctly to appropriately counsel couples. In this case series, we describe clinical scenarios where prospective parents were surprised to unexpectedly have a child with sickle cell disease, a haemoglobinopathy that causes severe clinical complications. Through these cases we demonstrate that deficiencies in testing can occur at different levels which may lead to incorrect estimation of the risk of having a child affected by a haemoglobinopathy. Consultation with a haematologist, laboratory medicine specialist, or genetic counsellor should be considered to select the appropriate test and interpret its results.

Objectives: Hemoglobinopathies are the commonest inherited blood disorders and form a serious burden worldwide, affecting communities, patient quality of life and healthcare resources. The Kingdom of Bahrain has issued a law obligating couples to undergo premarital screening to detect those at risk of having children affected with these disorders. The aim of this study was to analyze the marital decisions of couples at risk for hemoglobinopathies and follow up the outcomes., Methods: A retrospective study was conducted on couples at risk for hemoglobinopathies identified during the premarital screening program at local health centers in the Kingdom of Bahrain and referred to the genetics department in the Salmaniya Medical Complex for genetic counselling in 2018-2020., Results: A total of 189 couples were found to be at risk for hemoglobinopathies, of whom 159 completed the survey. Of these, 107 (67%) decided to proceed with their marriage and 26 couples achieved pregnancy. Out of 24 at-risk pregnancies with known outcome, 83.3% were spontaneous whereas only 16.7% underwent in-vitro fertilization (IVF) with preimplantation genetic diagnosis (PGD). Eight out of 20 infants born to couples after spontaneous conception were affected. A positive attitude toward IVF with PGD was held by 60% of at-risk couples., Conclusions: Despite undergoing premarital screening and genetic counselling, a large percentage of at-risk couples proceeded with their marriage. Most of them justified their decision due to the availability of advanced methods that aid in the prevention of having an affected child. However, the cost of such intervention was a major barrier for the majority of couples., Competing Interests: Declaration of conflicting interestsThe author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.

Background: In this study, we evaluated the impact of hemoglobin (Hb) variants on the performance of the Abbott Alinity c and Bio-Rad Variant II Turbo 2.0 HPLC Hb A1c assays., Methods: The analytical performance of the Abbott Alinity c Hb A1c (enzymatic) assay was compared to the Bio-Rad Variant II Turbo 2.0 HPLC method using leftover whole blood EDTA samples with and without the presence of a hemoglobin variant. Assay precision was determined from an analysis of controls. Bias was estimated from analysis of a set of 40 samples analyzed by a Tosoh G8 HPLC instrument at the University of Missouri Diabetes Diagnostic Laboratory, an NGSP Secondary Reference Laboratory., Results: Between-day precision was excellent for both methods (<3%). Bias met NGSP criteria of ±5% to target value. Correlation between the Alinity and Bio-Rad methods was good for patient samples without a hemoglobinopathy (y = 1.028x - 0.38, standard error of the estimate (SEE) = 0.16, n = 36, mean bias = -0.22). A total of 700 hemoglobin variant samples were evaluated on the 2 methods. Of the hemoglobin variants, 640/700 gave results on both methods: hemoglobin (Hb) S trait (n = 452), C trait (n = 131), D trait (n = 23), E trait (n = 26), and a mixture of other hemoglobinopathies (n = 8) including beta thalassemia, high hemoglobin F, transfused Hb SC, transfused Hb SD, and transfused Hb SS, or unknown variant. There was good agreement for the 640 Hb variants between the methods with a range of mean differences of -0.10 to +0.06 depending on the variant, but more variability (SEE 0.25 to 0.39). Sixty samples did not have paired results., Conclusions: To our knowledge, this study was the largest investigation of the effect of hemoglobinopathies on the Abbott Alinity c Hb A1c assay. Analytical performance varied depending on the specific hemoglobin variant trait when compared to the Bio-Rad Variant II Turbo 2.0 HPLC method., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hemoglobinopathies are one of the most widespread hereditary disorders in Turkey. The present study aimed to determine the prevalence of hemoglobinopathies in the Nigde province of Turkey. This study was conducted with 2013 individuals who applied for the premarital screening, between January 2019 and December 2021. The complete blood count was measured by an automated hematology analyzer. The types of hemoglobin were determined by high-performance liquid chromatography. A total of 2013 individuals including 951 (47.2%) females and 1062 (52.8%) males, were screened within the premarital screening program, and 67 (3.3%) of them were migrants. 53 out of 2013 (2.63%) individuals were identified as β thalassemia carriers, and five of them were migrants including two from Afghanistan, two from Iran, and one from Georgia. HbC was observed in two cases, a couple from Syria (0.1%), HbD in two cases (0.1%), HbE in one case from Thailand (0.05%), HbS-β-thalassemia in one case (0.05%), delta-β thalassemia in one case (0.05%), and unidentified structural variant in one case (0.05%). Moreover, 183 individuals (9.1%) were considered to have iron deficiency, α-thalassemia, or silent β-thalassemia carrier. These results indicate that the province of Nigde is a relatively risky region regarding hemoglobinopathies. Geographic location and immigrant population may have slightly affected the local prevalence of hemoglobinopathies and could be taken into consideration to ensure the effective implementation of the hemoglobinopathy prevention program.

Hemoglobinopathies are the most common single-gene disorders in humans. There are 1,424 variants of human hemoglobin described with 951 involving the β-globin gene. Ancestry and geography play a significant role in the incidence and nature of hemoglobinopathies, with African, Asian, and Mediterranean populations and their descendants being amongst the most affected. Investigation of variants in individuals of Hispanic descent is needed to reflect the changing demographics of the United States. Hemoglobin β-globin evaluation through gel electrophoresis, high-performance liquid chromatography, and HBB gene sequencing was performed on patients from Texas hospitals between 2010 and 2015 and demographic parameters (age, sex, ethnicity) was subsequently analyzed. A total of 846 patients underwent hemoglobinopathy evaluation. A β chain variant was detected in 628 of the 846 total patients. Hispanic patients represented 37% (314/846 patients), which were equally distributed between females (50%; 156/314) and males (50%; 156/314). A β-globin chain variant was found in 67% of Hispanic patients with a distribution across 10 variants seen in greater than 1% of patients. For hemoglobin variants, an understanding of the regional and ethnic prevalence will improve patient care through more effective screening and identification of the variant, early diagnosis, and appropriate treatment if necessary, and better genetic counseling.

Objectives: Hemoglobinopathies are a global public health problem with high mortality and morbidity and very expensive treatment. Disease can be reduced and prevented with hemoglobinopathy screening tests. It is possible to identify carriers with the hemoglobinopathy screening program applied in many countries of the world and in Turkey. This study aims to evaluate the results of the national premarital hemoglobinopathy screening program carried out in primary healthcare institutions., Methods: The research is of epidemiological and cross-sectional type. Electrophoresis results examined within the scope of the premarital hemoglobinopathy screening program in Samsun between 1 January 2019 and 31 December 2021 were evaluated retrospectively. Age, gender, year of screening, and hemoglobinopathy screening results were obtained from the records. In the statistical analysis of the data, p  < 0.05 was accepted., Results: The median age of 52,338 people screened under the hemoglobinopathy screening program was 29.0 (16.0-86.0) years. About 54.1% ( n  = 28,309) of those who were screened were female, and it was found that the least screening was done in 2020 ( n  = 15,765 (30.1%)). As a result of the screening, the frequency of the β-thalassemia (β-thal) trait was 1.37% ( n  = 676), the frequency of the abnormal HbS was 0.04% ( n  = 20). The frequency of β-thal trait was statistically significantly higher in 2020 (1.5%) compared to other years ( p  = 0.029). When the results were analyzed by gender, the rate of women with abnormal HbS (3.7%) was significantly higher than the others ( p  = 0.017)., Conclusions: This study presents the results of the national hemoglobinopathy screening program in Northern Turkey and the β-thal and the abnormal HbS rates were found to be low. The data obtained will be useful in monitoring hemoglobinopathy disorders and evaluating the current program's effectiveness in the future. It will allow decision-makers to implement policy changes and prioritize new programs.

Hemoglobin (Hb) Hammersmith, formed by serine substitution for phenylalanine at residue 42 in the beta-globin chain, is a very rare variant of unstable hemoglobin with low oxygen affinity. For patients with hemoglobinopathies, it is well-established that hematopoietic stem cell transplantation provides a complete cure, but the literature on its role for those with Hb Hammersmith is limited. A seven-month-old girl who was examined for anemia and splenomegaly was followed up for congenital hemolytic anemia. The patient with visible cyanosis of the lips and whose p50 was low in blood gas was diagnosed with Hb Hammersmith through the DNA sequence analysis. During the follow-up, frequent blood transfusions had to be given due to anemia aggravated by infections. Following a successful hematopoietic stem cell transplant from an HLA-matched sibling, the patient completely recovered from Hb Hammersmith. The case is presented because of its rarity.

Hemoglobinopathies are genetic disorders that affect the hemoglobin (Hb) molecule. Mutations in the alpha or beta chains altering the Hb tetramer may modify the molecule's oxygen-binding capacity. Hemoglobinopathies with low oxygen affinity may occur with cyanosis and an altered pulse oximetry reading, leading to unnecessary and sometimes invasive tests to rule out cardiovascular and respiratory conditions. In the case report described here, we present an asymptomatic pediatric patient who consulted for desaturated pulse oximetry. Her initial laboratory tests showed normocytic, normochromic anemia. Venous blood gas samples showed an elevated p50. After using extensive diagnostic tools, a variant of Hb with low oxygen affinity was diagnosed: Hb Denver., (Sociedad Argentina de Pediatría.)

Background: Oxford Nanopore Technology (ONT) third-generation sequencing (TGS) is a versatile genetic diagnostic platform. However, it is nonetheless challenging to prepare long-template libraries for long-read TGS, particularly the ONT method for analysis of hemoglobinopathy variants involving complex structures and occurring in GC-rich and/or homologous regions., Methods: A multiplex long PCR was designed to prepare library templates, including the whole-gene amplicons for HBA2/1, HBG2/1, HBD, and HBB, as well as the allelic amplicons for targeted deletions and special structural variations. Library construction was performed using long-PCR products, and sequencing was conducted on an Oxford Nanopore MinION instrument. Genotypes were identified based on integrative genomics viewer (IGV) plots., Results: This novel long-read TGS method distinguished all single nucleotide variants and structural variants within HBA2/1, HBG2/1, HBD, and HBB based on the whole-gene sequence reads. Targeted deletions and special structural variations were also identified according to the specific allelic reads. The result of 158 α-/β-thalassemia samples showed 100% concordance with previously known genotypes., Conclusions: This ONT TGS method is high-throughput, which can be used for molecular screening and genetic diagnosis of hemoglobinopathies. The strategy of multiplex long PCR is an efficient strategy for library preparation, providing a practical reference for TGS assay development., (© American Association for Clinical Chemistry 2023. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Hemoglobinopathies are highly prevalent in Saudi Arabia, with varying incidence rates across different regions. The Eastern and Jazan regions have the highest incidence rates. To prevent hemoglobinopathies, the premarital screening program (PMS) has been established in Saudi Arabia to identify at-risk couples before marriage. This cross-sectional descriptive study aimed to evaluate the awareness and attitude of young adults towards PMS in Jazan, Saudi Arabia, which involved 875 individuals (560 men and 315 women). The current study report significant association between sex, personal and family history of disease, and attitude towards PMS among young adults (P< 0.05). The study concludes that while there is a substantial level of awareness and positive attitude towards PMS among the population, there is a need for more detailed health campaigns led by healthcare providers, rulers, and Islamic leaders to highlight the importance of PMS as a preventative measure to reduce the incidence of hemoglobinopathies in Jazan, Saudi Arabia., Competing Interests: The Authors declared no conflict of interest, (African Journal of Reproductive Health © 2023.)

Background: We conducted a health technology assessment to evaluate the safety, effectiveness, and cost-effectiveness of carrier screening programs for cystic fibrosis (CF), fragile X syndrome (FXS), hemoglobinopathies and thalassemia, and spinal muscular atrophy (SMA) in people who are considering a pregnancy or who are pregnant. We also evaluated the budget impact of publicly funding carrier screening programs, and patient preferences and values., Methods: We performed a systematic literature search of the clinical evidence. We assessed the risk of bias of each included study using the Cochrane Risk of Bias tool and the Risk of Bias Assessment tool for Non-randomized Studies (RoBANS), and the quality of the body of evidence according to the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) Working Group criteria. We performed a systematic economic literature search and conducted cost-effectiveness analyses comparing preconception or prenatal carrier screening programs to no screening. We considered four carrier screening strategies: 1) universal screening with standard panels; 2) universal screening with a hypothetical expanded panel; 3) risk-based screening with standard panels; and 4) risk-based screening with a hypothetical expanded panel. We also estimated the 5-year budget impact of publicly funding preconception or prenatal carrier screening programs for the given conditions in Ontario. To contextualize the potential value of carrier screening, we spoke with 22 people who had sought out carrier screening., Results: We included 107 studies in the clinical evidence review. Carrier screening for CF, hemoglobinopathies and thalassemia, FXS, and SMA likely results in the identification of couples with an increased chance of having an affected pregnancy (GRADE: Moderate). Screening likely impacts reproductive decision-making (GRADE: Moderate) and may result in lower anxiety among pregnant people, although the evidence is uncertain (GRADE: Very low).We included 21 studies in the economic evidence review, but none of the study findings were directly applicable to the Ontario context. Our cost-effectiveness analyses showed that in the short term, preconception or prenatal carrier screening programs identified more at-risk pregnancies (i.e., couples that tested positive) and provided more reproductive choice options compared with no screening, but were associated with higher costs. While all screening strategies had similar values for health outcomes, when comparing all strategies together, universal screening with standard panels was the most cost-effective strategy for both preconception and prenatal periods. The incremental cost-effectiveness ratios (ICERs) of universal screening with standard panels compared with no screening in the preconception period were $29,106 per additional at-risk pregnancy detected and $367,731 per affected birth averted; the corresponding ICERs in the prenatal period were about $29,759 per additional at-risk pregnancy detected and $431,807 per affected birth averted.We estimated that publicly funding a universal carrier screening program in the preconception period over the next 5 years would require between $208 million and $491 million. Publicly funding a risk-based screening program in the preconception period over the next 5 years would require between $1.3 million and $2.7 million. Publicly funding a universal carrier screening program in the prenatal period over the next 5 years would require between $128 million and $305 million. Publicly funding a risk-based screening program in the prenatal period over the next 5 years would require between $0.8 million and $1.7 million. Accounting for treatment costs of the screened health conditions resulted in a decrease in the budget impact of universally provided carrier screening programs or cost savings for risk-based programs.Participants value the perceived potential positive impact of carrier screening programs such as medical benefits from early detection and treatment, information for reproductive decision-making, and the social benefit of awareness and preparation. There was a strong preference expressed for thorough, timely, unbiased information to allow for informed reproductive decision-making., Conclusions: Carrier screening for CF, FXS, hemoglobinopathies and thalassemia, and SMA is effective at identifying at-risk couples, and test results may impact preconception and reproductive decision-making.The cost-effectiveness and budget impact of carrier screening programs are uncertain for Ontario. Over the short term, carrier screening programs are associated with higher costs, and also higher chances of detecting at-risk pregnancies compared with no screening. The 5-year budget impact of publicly funding universal carrier screening programs is larger than that of risk-based programs. However, accounting for treatment costs of the screened health conditions results in a decrease in the total additional costs for universal carrier screening programs or in cost savings for risk-based programs.The people we spoke with who had sought out carrier screening valued the potential medical benefits of early detection and treatment, particularly the support and preparation for having a child with a potential genetic condition., (Copyright © King's Printer for Ontario, 2023.)

Background: δ-hemoglobinopathies may lead to misdiagnosis of several thalassemia syndromes especially β-thalassaemia carrier, it is important to evaluate the δ-globin gene defects in areas with high prevalence of globin gene disorders. We describe a prospective screening for δ-hemoglobinopathies in a routine setting in Thailand., Methods: Study was done on a cohort of 8,471 subjects referred for thalassemia screening, 317 (3.7%) were suspected of having δ-globin gene defects due to reduced hemoglobin (Hb) A 2 levels and/or appearance of Hb A 2 -variants on hemoglobin analysis. Hematologic and DNA analysis by PCR and related assays were carried out., Results: DNA analysis of δ-globin gene identified seven different δ-globin mutations in 24 of 317 subjects (7.6%). Both known mutations; δ -77(T>C) (n = 3), δ -68(C>T) (n = 1), δ -44(G>A) (n = 8), Hb A 2 -Melbourne (n = 5), δ IVSII-897(A>C) (n = 5), and Hb A 2 -Troodos (n = 1) and a novel mutation; the Hb A 2 -Roi-Et (n = 1) were identified. This Hb A 2 -Roi-Et, results from a double mutations in-cis, δ CD82(AAG>AAT) and δ CD133(GTG>ATG) , was interestingly found in combination with an in trans, 12.6 kb deletional δβ 0 -thalassemia in an adult Thai woman who had no Hb A 2 and elevated Hb F. A multiplex-allele-specific PCR was developed to detect these novel δ-globin gene defects., Conclusions: The result confirms a diverse heterogeneity of δ-hemoglobinopathies in Thailand which should prove useful in a prevention and control program of thalassemia in the region., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)