High Prevalence Of Hemoglobinopathies Research Articles

Addressing the Thalassemia Burden in Pakistan: The urgent need for a mandate on premarital screening

Dear Editor, Hemoglobinopathies are the most common recessively inherited single-gene genetic disorders around the world. Thalassemia is a genetic blood disorder that can be prevented. It has a high incidence rate in Mediterranean, Middle Eastern, and South Asian populations, making it the most prevalent genetic blood disorder globally.(1) The high prevalence of hemoglobinopathies is a significant public health concern. Pakistan has an estimated 10 million carriers of B-Thalassemia, with 5-7% carrier rate.(2) Every year, around 5000 children are diagnosed with B-Thalassemia major. Poverty, early marriages, consanguinity, limited awareness, rapid population growth, insufficient healthcare resources, and the scarcity of safe blood supplies exacerbate this issue. Practical strategies for mitigating the thalassemia burden have been implemented worldwide, providing healthcare professionals and the public with accurate information, counseling families, and premarital screening. Thalassemia screening before marriage has proven to be successful in other regions. In the MENA region, various countries have implemented premarital screening programs to prevent hemoglobinopathies and viral infections, proving immensely successful.(3) In Saudi Arabia, a reduction of over 70% in the prevalence of B-Thalassemia was documented six years after the introduction of the premarital screening program.(4) Similarly, a premarital screening program in Kuwait prevented the marriage of 50.4% of couples at risk over eleven years by issuing unsafe marriage certificates.(5) The success of premarital thalassemia screening programs in other countries is a testament to the potential of preventive measures. These international examples offer valuable insights on how Pakistan can alleviate the burden of thalassemia within its population. While increasing awareness among parents and families is crucial, a more comprehensive approach is necessary. Pakistan must focus on preventing the disease and introduce strict laws mandating premarital screening nationwide. Given the gravity of the thalassemia crisis in Pakistan and the proven success of premarital screening in other regions, the imperative for a nationwide mandate on premarital thalassemia screening cannot be overstated. Such legislation has the potential to substantially reduce the incidence of thalassemia by identifying carrier couples early in their relationship, thereby preventing high-risk marriages. By enacting and enforcing these laws, Pakistan can proactively address the root causes of this health issue and pave the way for a healthier and more informed future.

Premarital Screening for Thalassemia Among Young Adults: A Study in Zabol, Sistan and Baluchistan Province of Iran

Introduction: There is a high prevalence of hemoglobinopathies, including thalassemia, in Sistan and Baluchistan province of Iran. It is important to appropriately screen young adults to control the birth of new cases of thalassemia. In many less-equipped centers, this practice only relies on cell blood count. This study investigated the hematological parameters of young adults referring to the Central Laboratory of Sistan, Zabol, for premarital screening for thalassemia. Methods: This was a descriptive cross-sectional study conducted in Zabol, Sistan and Baluchistan province of Iran from August 2020 to August 2021. Complete blood count (CBC) parameters of 2926 young adults were collected using a Sysmex KX-21 device and were compared with available reference intervals according to the Clinical and Laboratory Standard Institute. Results: The means of women’s and men’s age were 38.84±16.32 and 36.64±14.14 years, respectively. The average values for each parameter in the studied population were red blood cell (RBC) (4.78±0.55), hemoglobin (13.19±2.46 g/dL), hematocrit (40.11±3.57%), mean corpuscular volume (MCV) (85.16±28.33), neutrophil (52.12±9.98), lymphocyte (37.84±9.03), mixed leukocytes (10.00±3.51), platelets (244.02±62.32). The mean values of hemoglobin (14.48±5.17 vs. 12.69±1.39 g/dL), hematocrit (43.01±3.89 vs. 38.97±3.45%), serum ferritin (115.4±74.3 vs. 69.20±12.36 g/dL), total iron-binding capacity (316.84±1.38 vs. 320.95±41.01, P=0.01), and serum iron (85.05±28.51 vs. 76.25±28.22, P=0.02) were significantly lower in women than in men. Out of 2,926 people who entered this study, 195 (6.66%) were suspected of having thalassemia because of their low MCV (71.61±7.33 fL) and mean corpuscular hemoglobin (MCH) (23.67±2.66 pg). Conclusion: The relatively low hemoglobin in females referring for premarital screening for thalassemia awakens healthcare experts to carefully examine these cases for the possibility of thalassemia minor after excluding other common possible reasons such as iron deficiency anemia using iron studies and hemoglobin electrophoresis.

High-performance liquid chromatography local reference ranges of hemoglobin fractions (HbA, HbA2, and HbF) in detection of hemoglobinopathies in western Kenya

High-performance liquid chromatography local reference ranges of hemoglobin fractions (HbA, HbA2, and HbF) in detection of hemoglobinopathies in western Kenya

A Different Look at Premarital Hemoglobinopathy Screening in Primary Care

Objective: Despite the high prevalence of hemoglobinopathies (HBP), the most common single-gene disorders in Turkey, data in some regions are lacking. 
 We aimed to evaluate the effectiveness of the hemoglobinopathy premarital screening program (PMS) and to investigate the contribution of efficient use of complete blood count (CBC) parameters on cost-effectivity.
 Method: Hemoglobinopathy diagnosed 49171 subjects in 4 years and CBC of subjects with hemoglobinopathy in a year were evaluated retrospectively.
 Result: The total incidence rate of HBP was 3.41%, β-thalassemia trait (β-TT) was 1.98%, Hemoglobinopathy incidence in the PMS group was 2.43%, β-TT was 1.08%. Moreover, HbF, HbD, HbC, HbS, HbE and HbJ were detected with the incidences of 0.49%, 0.14%, 0.05%, 0.04%, 0.007% and 0.009%, respectively. RDW/MCH ratio compared to other indices was the most successful for both sexes in diagnostic efficiency of HBP (AUC: male:0.922 - female:0.961) and β-TT (AUC: male;0.928 - female:0.961). 
 Conclusion: PMS was found to be an effective application program in hemoglobinopathy screening. RDW/MCH ratio was the most useful and easy parameter in detecting HBP and β-TT in PMS and in terms of reducing unnecessary test requests and cost-effectiveness in public health screenings.

Misleading HbA1c Measurement in Diabetic Patients with Hemoglobin Variants.

Background and Objectives: Hemoglobin A1c (HbA1c) is widely used for the monitoring and management of diabetes mellitus. The aim of this study is to investigate the influence of hemoglobin (Hb) variants on the measurement of HbA1c. Materials and Methods: HbA1c levels of 845 blood samples obtained from diabetic patients with various hemoglobin types were measured using a turbidimetric inhibition immunoassay and capillary electrophoresis. Results: Of 845 patients with diabetes, 65.7% (555/845) have the normal hemoglobin type (A2A) and 34.3% (290/845) have various abnormal hemoglobin types, including heterozygous HbE 30.2% (255/845), homozygous HbE 1.9 % (16/845), Hb Constant Spring (CS) trait 1.4% (12/845), CSEA Bart’s 0.2% (2/845), and beta-thalassemia trait 0.6% (5/845). In most of the patients with diabetes, HbA1c levels determined by two different methods, inhibition immunoassay and capillary electrophoresis, gave strong positive correlation (R = 0.901, P < 0.001), except for those with homozygous HbE (N = 16) and CSEA Bart’s (N = 2). In all 18 patients with homozygous HbE and CSEA Bart’s, the HbA1c was undetectable by capillary electrophoresis, meaning that their estimated average glucose was undeterminable, although their HbA1c levels could be measured using an inhibition immunoassay. The discrepancy of HbA1c results obtained from two different methods is noted in patients without HbA. Conclusions: We have demonstrated the erroneous nature of HbA1c measurement in patients with hemoglobin variants, especially in those without HbA expression. Therefore, in the population with a high prevalence of hemoglobinopathies, hemoglobin typing should be considered as basic information prior to HbA1c measurement.

Influence of hemoglobinopathies and glucose-6-phosphate dehydrogenase deficiency on diagnosis of diabetes by HbA1c among Tanzanian adults with and without HIV: A cross-sectional study.

IntroductionHemoglobin A1c (HbA1c) is recommended for diagnosing and monitoring diabetes. However, in people with sickle cell disease (SCD), sickle cell trait (SCT), α-thalassemia or glucose-6-phosphate dehydrogenase (G6PD) deficiency, HbA1c may underestimate the prevalence of diabetes. There are no data on the extent of this problem in sub-Saharan Africa despite having high prevalence of these red blood cell disorders.MethodsBlood samples from 431 adults in northwestern Tanzania, randomly selected from the prospective cohort study, Chronic Infections, Comorbidities and Diabetes in Africa (CICADA), were analysed for SCT/SCD, α-thalassemia and G6PD deficiency and tested for associations with the combined prevalence of prediabetes and diabetes (PD/DM) by HbA1c, using the HemoCue 501 HbA1c instrument, and by 2-hour oral glucose tolerance test (OGTT).ResultsThe mean age of the participants was 40.5 (SD11.6) years; 61% were females and 71% were HIV-infected. Among 431 participants, 110 (25.5%) had SCT and none had SCD. Heterozygous α-thalassemia (heterozygous α+ AT) was present in 186 (43%) of the participants, while 52 participants (12%) had homozygous α-thalassemia (homozygous α+ AT). Furthermore, 40 (9.3%) participants, all females, had heterozygous G6PD deficiency while 24 (5.6%) males and 4 (0.9%) females had hemizygous and homozygous G6PD deficiency, respectively. In adjusted analysis, participants with SCT were 85% less likely to be diagnosed with PD/DM by HbA1c compared to those without SCT (OR = 0.15, 95% CI: 0.08, 0.26, P < 0.001). When using OGTT, in adjusted analysis, SCT was not associated with diagnosis of PD/DM while participants with homozygous α+ AT and hemizygous G6PD deficiency were more likely to be diagnosed with PD/DM.ConclusionsHbA1c underestimates the prevalence of PD/DM among Tanzanian adults with SCT. Further research using other HbA1c instruments is needed to optimize HbA1c use among populations with high prevalence of hemoglobinopathies or G6PD deficiency.

Genetic epidemiology of hemoglobinopathies among Iraqi Kurds.

Hemoglobinopathies are major health problems among Iraqi Kurds, who are a distinct ethnic group inhabiting North and Northeastern Iraq. We reviewed published literature on these disorders in this part of the world, and it was revealed that the most prevalent is β-thalassemia with carrier rates of 3.7-6.9%. Alpha thalassemia is less prevalent with carrier rates of0.03-1.22%, while the sickle cell gene is variably distributed with carrier rates of 0.06-1.2%. Other structural hemoglobinopathies and δβ-thalassemia are sporadic. Twenty-seven different β-thalassemia mutations were identified, with seven constituting 82% of 1039 chromosomes characterized, namely: IVS-II-1 (G>A), IVS-I-6 (T>C), IVS-I-I (G>A), codon 8 (-AA), codon 8/9 (+G), IVS-I-110 (G>A), and codon 5 (-CT). There were notable regional variations in the distribution of β-thalassemia mutations, with Cd44 being mainly prevalent in the North, while IVS-I-110 is mainly prevalent in the East. In relevance to α-thalassemia, ten different mutations were detected, with the four most frequent constituting 92.4% of 262 alleles characterized being: -α3.7, --MED, α-5ntα, and αPolyA1α. In relevance to sickle cell gene, it is seen in the northern part of the region bordering Turkey, with comparable prevalence rates, and is associated, similar to Turkey, mainly with the Benin haplotype, unlike that in Southern Iraq where it is associated with the Arab-Indian haplotype, similar to Eastern Arabian Peninsula. Given the high prevalence of hemoglobinopathies in the region, and the high rates of consanguineous marriages, a preventive program was initiated in 2008, and results of its first 5 years were promising, though there are still many outstanding challenges that require addressing.

Prevalence of Gaucher Disease in Patients of Unknown Cause of Splenomegaly and/or Thrombocytopenia in Saudi Arabia

Rationale: Gaucher disease (GD) is the most common amongst the lysosomal storage disorders. Prevalence of GD in Saudi Arabia is not available in published literature and it is expected to be high and remains undiagnosed. In 2004, a Saudi study reported that GD accounts for 6% of all genetic metabolic disorders. While acid sphingomyelinase deficiency (ASMD) is a rare progressive genetic disorder with no clear data about its incidence in Saudi Arabia. Consequently, this study proposes to determine the prevalence of GD and ASMD in outpatient settings in Saudi Arabia by screening patients with unknown causes of splenomegaly and/or thrombocytopenia. These data will change the local practice and increase the awareness towards GD and ASMD in Saudi Arabia. Objectives: To determine the prevalence of GD in high risk group (defined as patients with splenomegaly and/or thrombocytopenia of unknown cause) and describe their characteristics. We also aim to determine the prevalence of ASMD in high risk group. Methods: A multi-center, observational, study will be conducted in 25 specialty care centres across Saudi Arabia, these centres are mainly focusing on pediatric hematology, adult hematology and hemato-pathology. Female or male patients (aged 2-75 years) will deemed eligible if they have clinical, instrumental or laboratory signs of splenomegaly or thrombocytopenia over a period of 12 months without definitive cause. These patients will be tested for acid β-glucosidase and acid sphingomyelinase enzymes activity on dried blood spot (DBS) samples. Patients with hematological malignancies, hemolytic anemia, and/or thalassemia (except sickle cell disease) will be excluded. A total of 400 patients from Saudi Arabia who fulfill the eligibility criteria will be enrolled in the study. All patient data will be collected in a single visit. Each enrolled patient will visit the investigator for a baseline visit. The investigator will contact them later for sharing the investigation blood test results. During the baseline visit, data and blood sample for enzyme tests and genotyping will be collected by the investigator/designated person at the site. Discussion: Arab world represents one of the leading regions in terms of the incidence of congenital and genetic disorders; a growing body of published literature reported a notable trends towards higher incidence of congenital and genetic diseases, compared to other parts of the world(1). High consanguinity rates which reach up to 60% in some regions, high prevalence of haemoglobinopathies and metabolic disorders, relatively high maternal and parental age, and lack of proper genetic screening were reported as contributing factors for this high prevalence of genetic disorders in the Arab world(1-3). In Saudi Arabia, the situation appears to be no different as previous retrospective studies showed a relatively high incidence of genetic diseases such as inborn error of metabolism. The data of the present study will change the local practice and increase the awareness towards GD and ASMD in Saudi Arabia.

The evolution of clinical research in thalassaemia: where has all the funding gone?

In this issue of the British Journal of Haematology, a study is published on the various comorbidities and premature mortality of English patients with transfusion-dependent thalassaemia.1 A total of 612 such patients were identified, which is estimated to be approximately 85% of these patients who reside in England. Their crude 10-year mortality was over five times that of the general population (age- and sex-matched) and the median age at death was 45 years.1 Ethnicity data, available for 94% of the patients, most commonly showed an Asian origin (57% of the total), which included Pakistani, Indian, Bangladeshi and others. By way of comparison, three recent publications also describe the clinical outcome of patients with transfusion-dependent thalassaemia. One is from South India,2 in which 1 087 patients were studied. Their median survival was 26·9 years and they had many undertreated complications such as iron overload and transfusion-transmitted diseases. The mortality for children under 5 years of age was seven times higher than in the general population.2 The other two publications are from Italy. In one, the authors report that the median survival for Italian thalassaemia patients was not reached and the Kaplan–Meier analysis showed 75% survival at age approximately 50 years for both transfusion-dependent and non-transfusion-dependent patients.3 A more recent publication from Italy discusses the challenges of treating the ageing thalassaemia patient population.4 There are estimated to be around 6 000 patients with symptomatic thalassaemia in Italy who have a variety of health issues and require ongoing medical intervention which is given exclusively in specialized centres.4 These studies demonstrate that a major gap still exists in the care and prognosis of patients with thalassaemia, between regions of economic deprivation and regions with optimal health care. However, another significant difference in these studies is their funding. The study from India was funded by two philanthropic organizations based in India, as well as an international philanthropic organization and an Indian data management company. This company, which provided funding and co-authored the study, produces software for management of blood banking and haematological diseases. The study of Vitrano et al.3 was funded by a private Italian philanthropic organization which is dedicated to the care and research of thalassaemia. The study by Pinto et al.4 received no funding. The funding (and co-authorship) for the study published in this issue1 came from a biotechnology company which produces a retroviral vector for gene therapy. This group of studies highlights the diminishing resources for epidemiological and demographic studies of thalassaemia and its complications. Funding for medical research in general has decreased in the past years. Most sources of funding for thalassaemia have been channelled into either basic science or translational research or studies related to therapy, which are worthy areas for research. Nonetheless there is still a need for studies of outcome such as those cited above, for two reasons: (i) to highlight that globally, there is still much to strive for in terms of basic supportive care of thalassaemia patients, and disease prevention; and (ii) to evaluate the status of the thalassaemia patients residing in every country. Global migration is influencing the epidemiology of thalassaemia in the same way as has been documented for sickle cell anaemia.5 Countries such as the UK and USA have received a net influx of immigrants from countries with a high prevalence of haemoglobinopathies, such as Pakistan, Brazil and India,5 where thalassaemia is also common. Thus, the demography of patients is in a state of flux, and periodic re-evaluation is necessary in every country. Funding for such clinical studies is not readily available and some studies are performed by the researchers themselves without funding. Potential funding sources such as the Cooley’s Anemia Foundation in the USA and the Thalassemia Foundation of Canada generally support local research which is treatment-oriented (as can be seen from the list of projects funded, available on the organizations’ websites). Sizeable funding such as that from the National Institutes of Health is highly competitive and generally supports major projects in the fields of molecular biology and gene therapy.6 Thus, clinical studies of morbidity and survival in the developed world may be funded and even co-authored by corporate sources, as in the studies performed in India2 and England.1 The important consideration is not the funding source, but that the data is impartially presented and is made public for planning and resource allocation, both for the care of patients and for prevention of this serious disease. The manuscript was written entirely by Deborah Rund. No funding was received for the writing and preparation of the manuscript.

Implications of Population Screening for Thalassemias and Hemoglobinopathies in Rural Areas of West Bengal, India: Report of a 10-Year Study of 287,258 Cases

Thalassemia and hemoglobinopathies are the most common cause of high morbidity and mortality in India. Detection of carriers and premarital counseling play an important role in preventing the birth of a thalassemic child. The present study aimed to detect large numbers of asymptomatic carriers in rural areas of West Bengal, India. The present cross-sectional study was conducted over a period of 10 years. Thalassemia awareness programs and detection camps were organized at the community level. After signed written consent was obtained, the collected blood samples were subjected to a complete blood count (CBC) in an automated blood cell counter and then analyzed by high performance liquid chromatography (HPLC); in difficult cases, samples were sent to the reference laboratory for molecular characterization. Out of 287,258 samples collected, 32,921 (11.46%) cases revealed abnormal hemoglobins (Hbs); of these, 31,782 (11.06%) carried heterozygous states (carriers/traits), and the remainder were either homozygous or compound heterozygous for different hemoglobinopathies. Two common variants were revealed in the study, namely β-thalassemia (β-thal) (7.23%) and Hb E [β26(B8)Glu→Lys, HBB: c.79G>A] (2.77%) traits. Among homozygous or compound heterozygous states, Hb E/β-thal (0.14%) and β-thal major (β-TM) (0.12%) were predominant. In rural areas of West Bengal, the most common Hb variants detected were β-thal and Hb E traits. In view of the high prevalence of hemoglobinopathies in this region, routine premarital screening and genetic counseling should be emphasized and encouraged to prevent the birth of a thalassemic child, and thus curtailing the burden on families and the health economy.

Prevalence of Hemoglobinopathies (β-Thalassemia and Sickle Cell Trait) in the Adult Population of Al Majma’ah, Saudi Arabia

Despite the high prevalence of hemoglobinopathies in Saudi Arabia, the prevalence data in some regions are lacking. Updating the epidemiological survey of hemoglobinopathies at regular intervals is necessary to develop effective prevention and control strategies. Therefore, the primary aim of this study was to determine the prevalence of selected hemoglobinopathies in Saudi adults attending premarital screening at the King Khaled General Hospital (KKGH), Al Majma’ah, Saudi Arabia. The current retrospective study was approved by the Central Institutional Review Board (IRB) of the Ministry of Health (with central IRB log #2019-0039E) and was carried out at the above hospital. The data of the premarital couples, who attended the premarital screening center at KKGH from 1 October 2016 to 30 September 2019, was included in this study. A cation exchange high performance liquid chromatography (HPLC) system was used for screening of the selected hemoglobinopathies. In total, 3755 cases including 1953 (52.01%) males and 1802 (47.99%) females, were screened for hemoglobinopathies. Abnormal hemoglobin (Hb) fractions were observed in 38 (1.01%) cases. The prevalence of β-thalassemia (β-thal) trait was 0.69% (26/3755) and that of sickle cell trait 0.32% (12/3755). Our results showed that the prevalence of β-thal trait is higher than that of sickle cell trait in the adult population of Al Majma’ah. Further comprehensive programs should be carried out to determine the prevalence of hemoglobinopathies in various provinces and cities of Saudi Arabia and other countries. This will help to maintain the updated records of the disease incidence for improving the control measures.

Greatalys: Generating Real World Evidence across Italy in Sickle Cell Disease

Background: Sickle Cell Disease (SCD) is a severe, potentially life threatening hereditary hemoglobin disorder requiring multidisciplinary care including screening, prevention, health education and management of acute and chronic complications. [ME Houwing et al, Blood Rev 2019] Although it affects millions of people throughout the world mainly individuals of African descent, Mediterranean (Caucasian) and Asiatic population, global migration from regions where the disease is endemic are changing its geographical distribution with a significant impact on patient survival, quality of life and costs for health systems requiring new treatment and preventive approaches. Data on epidemiological and clinical profiles of SCD have deeply changed also in Italy, a country with a high prevalence of hemoglobinopathies and where SCD is already present in the native population, due to an increasing number of immigrants from countries with high disease prevalence. Currently, approximately 2,000 SCD patients live in Italy. The creation of an Italian National Registry of Thalassemia and Hemoglobinopathies - was approved in 2017 thanks to a strong joint initiative of the Italian Society of Thalassemias and Hemoglobinopathies (SITE) and national patients associations. However the Registry is not yet completed, thus, the information currently available is very limited. [G Russo et al, Orphanet J Rare Dis. 2019] The Italian National Health Service is organized in Regions and Local Health Units (LHU). Each LHU reimburses health providers (eg, public and private hospital, general practitioners, outpatient services providers) for health assistance provided to citizens referring to the LHU, and uses specific databases to track the health assistance provided containing useful data to describe the type of assistance (eg, patient beneficiary, date of assistance) and to calculate the related charge. The main purpose of GREATalyS trial (CSEG101AIT01) is to collect data on SCD which may be representative of the national picture to better understand the burden of illness in terms of patient population, key disease features and resources consumption in Italy. Methods: Observational retrospective analyses will be carried out by integrating administrative databases for healthcare resources consumption (pharmaceuticals database, hospitalizations database, diagnostic tests and specialist visits database) from a sample of Italian Regions and LHUs, geographically distributed across the National territory (balanced between regions and number of covered residents). A representative sample of the whole national landscape through the involvement of approximately 11 LHUs and Regions will allow capture of approximately 23 million covered residents, representing about 38% of the entire Italian population. Patient Socio-Demographic characteristics (age, gender), all hospitalizations (SCD related and not related), previous SCD treatment type, co-morbidity profiles, patient treatment patterns, resources use and health services cost will be collected and analyzed. Anonymized patient data will be extracted into the Hospitalization database searching the relevant International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM codes). All analyses will be performed by STATA SE, version 12.0. The Local Ethics Committee of each participating Region/LHU has been notified about the study. Objectives: Composite objectives will collect both epidemiological and burden of illness data. Primary study objective is to estimate SCD prevalence and incidence rate from January 2010 to December 2018. Key secondary objectives include description of demographic and clinical characteristics, therapeutic pathways, health care resource use and direct costs (derived from health care resource utilization in term of drug treatments, diagnostic tests, specialist visits and hospitalizations) for patients affected by SCD. Conclusions: GREATalyS is to our knowledge the first SCD real world evidence study in Italy leveraging National Health System administrative databases to collect epidemiological and burden of illness data, and represents a useful health assessment model to better understand the evolving scenario in Italy, a country where SCD is becoming an emerging health problem. Figure Disclosures Castiglioni: Novartis Farma SpA: Employment. Condorelli:Novartis Farma SpA: Employment. Amore:Novartis Farma SpA: Employment. Perrone:CliCon srl: Employment. Alessandrini:CliCon srl: Employment. Veronesi:CliCon srl: Employment. Degli Esposti:CliCon srl: Employment. Premoli:Novartis Farma SpA: Employment. Fiocchi:Novartis Farma SpA: Employment.

Prevalence of Various Hemoglobinopathies-An Experience from Tertiary Care Centre

Objective: To find out the prevalence of thalassemias and various other hemoglobinopathies in state of Haryana and to assess the role of High performance liquid chromatography (HPLC) for accurate and quick diagnosis of various hemoglobin disorders. Methods: This study was conducted in Pt. B. D. Sharma, PGIMS, Rohtak from July 2010 to October 2016 for hemoglobin variant screening by HPLC of total of 4275 patients, selected through multistage random sampling technique. Results: Among 4275 total cases surveyed, normal hemoglobin pattern was observed in 3862 (90.3%) and abnormal hemoglobin fractions on HPLC were detected in 413 (9.7%). Βeta (β) thalassemia trait was predominant abnormality found in a total of 318 cases (7.4%). There were 19 cases of β-thalassemia major and 24 of β-thalassemia intermedia. Other abnormal patterns found were HbE (trait in 11 and HbE disease in 6 cases), Hb S (2 cases each of sickle cell disease and sickle cell trait), 2 cases of high Hb F (1 case each of heterozygous and homozygous HPFH), 11 cases of Hb D Punjab along with 2 cases of Hb D Iran, 1 case of Hb C and 2 cases each of double heterozygotes for Hb E/ β-thalassemia and Hb S/ β-thalassemia. Conclusion: There is high prevalence of hemoglobinopathies in this region and HPLC forms a rapid and accurate tool in early detection and management of various hemoglobinopathies.

The Effect of 12-weeks of Daily Iron Supplementation on Non-transferrin Bound Iron Concentrations in Women with a High Prevalence of Hemoglobinopathies (P10-113-19)

ObjectivesOur aim was to assess serum NTBI concentrations in non-pregnant Cambodian women who received daily iron supplements (60 mg elemental iron as ferrous sulfate) in accordance with the 2016 global World Health Organization (WHO) guidelines. MethodsSerum NTBI concentration was measured with the use of the FeROS™ eLPI assay (Afferix Ltd., Israel) in fasting venous blood samples collected during a 2015 supplementation trial among predominantly anemic Cambodian women (18–45 years). Samples were randomly selected from sub-groups of women who received 60 mg daily elemental iron as ferrous sulfate (n = 50) or a placebo (n = 50) for 12-weeks. ResultsOverall, n = 17/100 (17%) of women had an elevated serum NTBI concentration (≥0.1 μmol/L) at 12-weeks; n = 9 in the Fe group and n = 8 in the placebo group. Of the n = 100 women, a total of 82% of the women were iron-replete (n = 82/100, inflammation-adjusted ferritin >15 μg/L) and 67% (n = 67/100) had some form of a hemoglobinopathy (namely, Hb E variants or α-thalassemia). Elevated serum NTBI concentration was not associated with age, iron supplementation, transferrin saturation or severe hemoglobinopathies (P >0.05). ConclusionsIn this population of Cambodian women with a high prevalence of hemoglobinopathies, we found that daily iron supplementation was not associated with elevated serum NTBI concentrations at 12-weeks, as compared to placebo. Funding SourcesInternational Life Sciences Institute (ILSI) North America.

The Effect of Daily Iron Supplementation with 60 mg Ferrous Sulfate for 12 Weeks on Non-Transferrin Bound Iron Concentrations in Women with a High Prevalence of Hemoglobinopathies.

There is a lack of evidence for the safety of untargeted daily iron supplementation in women, especially in countries such as Cambodia, where both anemia and hemoglobinopathies are common. Our aim was to assess serum non-transferrin bound iron (NTBI), a toxic biochemical that accumulates in blood when too much iron is absorbed, in Cambodian women who received daily iron supplements in accordance with the 2016 global World Health Organization (WHO) guidelines. We used fasting venous blood samples that were collected in a 2015 supplementation trial among predominantly anemic Cambodian women (18–45 years). Serum NTBI was measured with use of the FeROS™ eLPI assay (Aferrix Ltd., Tel-Aviv, Israel) in randomly selected sub-groups of women who received 60 mg daily elemental iron as ferrous sulfate (n = 50) or a placebo (n = 50) for 12 weeks. Overall, n = 17/100 (17%) of women had an elevated serum NTBI concentration (≥0.1 μmol/L) at 12 weeks; n = 9 in the Fe group and n = 8 in the placebo group. Elevated serum NTBI concentration was not associated with age, iron supplementation, transferrin saturation or severe hemoglobinopathies (p > 0.05). In this population of women with a high prevalence of hemoglobinopathies, we found that daily iron supplementation was not associated with elevated serum NTBI concentrations at 12 weeks, as compared to placebo.

New Challenges in Diagnosis of Haemoglobinopathies: Migration of Populations

The current influx of economic migrants and asylum seekers from countries with a high prevalence of haemoglobinopathies creates new challenges for health care systems and diagnostic laboratories. The migration of carriers introduces new and novel haemoglobinopathy mutations to the diagnostic repertoire of a laboratory, often creating new pressures to improve and update the carrier screening technology and diagnostic scope. For antenatal screening programmes, the marriage of partners from different ethnic groups can lead to the risk of compound heterozygote children being born novel mutation combinations, creating problems in the provision of accurate advice regarding the expected phenotype of the thalassaemia or haemoglobinopathy disorder. In the UK, the impact of immigration required the National Haemoglobinopathy Reference laboratory to change the strategy and techniques used for the molecular diagnosis of thalassaemia and the haemoglobinopathies. In 2005, due to the increasingly large range of β-thalassaemia mutations that needed to be diagnosed, the laboratory switched from a three-step screening procedure using ARMS-PCR to a simpler but more expensive one-step strategy of DNA sequencing of the beta and alpha globin genes for all referrals. After ten years of employing this strategy, a further 57 novel thalassaemia and haemoglobionpopthy alleles were discovered (11 new β-chain variants, 15 α-chain variants, 19 β-thalassaemia mutations and 12 α+-thalassaemia mutations), increasing further the extremely heterogeneous spectrum of globin gene mutations in the UK population.

The ‑α3.7 deletion in α‑globin genes increases the concentration of fetal hemoglobin and hemoglobin A2 in a Saudi Arabian population

The regions of Al‑Qatif and Al‑Ahssa in the Eastern Province of Saudi Arabia are known for their high prevalence of hemoglobinopathies, including β‑thalassemia and sickle cell anemia. Previously, the α‑gene deletion has been demonstrated as highly prevalent among populations residing in these two regions. The present study was conducted in order to investigate the implications of the α‑globin gene deletion on fetal hemoglobin (HbF) and hemoglobin α2 (HbA2) concentrations in patients with transfusion‑dependent β‑thalassemia. A total of 166 Saudi patients with transfusion‑dependent β‑thalassemia and 337 healthy Saudi patients were included in the study. The ‑α3.7, ‑α4.2, -‑FIL, -‑SEA, -‑MED and -‑(20.5) gene deletions were identified using multiplex α‑globin deletion polymerase chain reaction. The present study revealed that the ‑α3.7 gene deletion is the most prevalent (43.5%) in the Saudi populations that were analyzed and is characterized by the deletion of 3,804 base pairs. Numerous genotypes, namely ‑3.7α2/α1α2, ‑3.7α2/α1α12, ‑3.7α2/‑3.7α2, ‑3.7α2HphI/α1α2HphI, ‑3.7α2/α1‑4.2, ‑3.7α2/α1polyA‑1α2, ‑3.7α12/α1α12, ‑‑FIL/‑3.7α2 and ‑3.7α2/‑3.7α2Hb Villiers le Bel were also identified in the investigated population. Furthermore, a gradual increase in the concentration of HbF and HbA2 in patients with β‑thalassemia and the number of α‑gene deletions was demonstrated; whereas in healthy patients the level of HbA2 was demonstrated to decrease as the number of α‑gene deletions increased. Therefore, it can be concluded that the high HbF concentration in the present study is predominantly associated with other mutations associated with β‑thalassemia rather than α‑globin deletions. Furthermore, the results of the present study also revealed novel α‑gene deletion genotypes prevalent in the population studied, namely α1α2/α1α2HphI, α1α2HphI/α1α2HphI, α1α2/α1α2Hb Handsworth, ‑3.7α2HphI/α1α2HphI, ‑3.7α2/‑3.7α2Hb Villiers le Bel and ‑-MED/α1α2HphI.

Co-inheritance of α-thalassaemia and β-thalassaemia in a prenatal screening population in mainland China.

To determine the prevalence of α-thalassaemia in β-thalassaemia individuals in a Chinese population. The standard diagnostic marker for β-thalassaemia was elevation of the Hb A2 level (>3.5%) with low mean corpuscular volume. The common α-thalassaemia mutations were studied by molecular analysis in all identified β-thalassaemia carriers. A prevalence rate of 3.3% for β-thalassaemia was found in our population; α- and β-thalassaemia interactions were found to co-exist in 17.8% of the β-thalassaemia carriers. The -SEA deletion was the most common α-thalassaemia mutation co-inherited with β-thalassaemia, followed by the -α3.7 deletion, the -α4.2 deletion, Hb Quong Sze, and Hb Constant Spring. Our results suggest that it could be valuable to study co-existing α-globin mutations in subjects with β-thalassaemia trait in a prenatal screening programme, especially in populations with a high prevalence of haemoglobinopathies.

Characterizing a Cohort of α-Thalassemia Couples Collected During Screening for Hemoglobinopathies: 14 Years of an Iranian Experience

Our study aimed to determine the number of couples with normal hemoglobin (Hb) electrophoresis and low-borderline hematological values, which may come up with a clinically critical status in their offspring. The number of couples at risk for severe α-thalassemia (α-thal) needed to be estimated before recommending genetic counseling and prenatal diagnosis (PND). During the past 14 years, from at least 7000 referrals, 754 couples were investigated for α-thal by direct mutation detection methods followed by reverse strip assay and α-globin gene sequencing for inconclusive cases. Detection of silent β-thalassemia (β-thal) mutations was done in suspected cases by complete β-globin gene sequencing. We were able to provide a molecular diagnosis in 87.3% (658/754) of couples. A total of 9.1% (60/658) may have a clinically significant hemoglobinopathy in their offspring. Significant conditions included hydrops fetalis (20.0%; 12/60), certain Hb H (β4) genotypes (78.3%; 47/60) and β-thal intermedia (β-TI) (1.7%; 1/60). The diagnostic flowchart for couples with microcytic hypochromic anemia in countries with a high prevalence of hemoglobinopathies should include α and β gene sequencing. As our results indicate, every nine out of 100 of these couples will face significant hemoglobinopathies and every two out of 100 can carry Hb Bart’s (γ4) hydrops fetalis in their pregnancies. For such cases, PND should be utilized to allow the carrier couples to decide whether or not to abort the fetus.

Screening for Type 1 and Type 2 Diabetes

Screening for Type 1 and Type 2 Diabetes