Impact of a national β-thalassemia carrier screening program on the birth rate of thalassemia major

CONTEXT: Tay-Sachs disease is an autosomal recessive disease characterized by progressive neurologic degeneration, fatal in early childhood. In the Ashkenazi Jewish population the disease incidence is about 1 in every 3,500 newborns and the carrier frequency is 1 in every 29 individuals. Carrier screening programs for Tay-Sachs disease have reduced disease incidence by 90% in high-risk populations in several countries. The Brazilian Jewish population is estimated at 90,000 individuals. Currently, there is no screening program for Tay-Sachs disease in this population. OBJECTIVE: To evaluate the importance of a Tay-Sachs disease carrier screening program in the Brazilian Jewish population by determining the frequency of heterozygotes and the acceptance of the program by the community. SETTING: Laboratory of Molecular Genetics - Institute of Biosciences - Universidade de São Paulo. PARTICIPANTS: 581 senior students from selected Jewish high schools. PROCEDURE: Molecular analysis of Tay-Sachs disease causing mutations by PCR amplification of genomic DNA, followed by restriction enzyme digestion. RESULTS: Among 581 students that attended educational classes, 404 (70%) elected to be tested for Tay-Sachs disease mutations. Of these, approximately 65% were of Ashkenazi Jewish origin. Eight carriers were detected corresponding to a carrier frequency of 1 in every 33 individuals in the Ashkenazi Jewish fraction of the sample. CONCLUSION: The frequency of Tay-Sachs disease carriers among the Ashkenazi Jewish population of Brazil is similar to that of other countries where carrier screening programs have led to a significant decrease in disease incidence. Therefore, it is justifiable to implement a Tay-Sachs disease carrier screening program for the Brazilian Jewish population.

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DNA-based carrier screening in primary healthcare: screening for aspartylglucosaminuria mutations in maternity health offices

Clinical Chemistry ◽

10.1093/clinchem/42.9.1398 ◽

1996 ◽

Vol 42 (9) ◽

pp. 1398-1404 ◽

Cited By ~ 10

Author(s):

M Hietala ◽

P Aula ◽

A C Syvänen ◽

A Isoniemi ◽

L Peltonen ◽

...

Keyword(s):

Primary Healthcare ◽

Large Scale ◽

Solid Phase ◽

Screening Program ◽

Low Cost ◽

Carrier Screening ◽

Screening Programs ◽

One Step ◽

Laboratory Technology ◽

Maternity Health

Abstract Large-scale genetic screening programs are complex enterprises in which ethical, technical, medical, and socioeconomic aspects have to be handled with professional expertise. Establishment of automated, relatively robust, and inexpensive laboratory techniques is one step of this path. Here a pilot carrier-screening program for the mutations causing aspartylglucosaminuria was carried out for pregnant women in primary care maternity health offices. Women (1975) were tested before their 12th week of pregnancy, and 31 heterozygotes were detected. The sampling was based on dried blood strips, facilitating convenient handling and inexpensive mailing to the laboratory. The mutation detection technique, solid-phase mini-sequencing simplified by the use of scintillation microplates and automated equipment, proved to be rapid, simple, inexpensive, and reliable, with a low repeat rate (2.5%). In conclusion, we found that good collaboration between the primary healthcare unit, the laboratory, and counseling experts, combined with modern laboratory technology, facilitate reliable low-cost genetic testing.

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The Israeli national population program of genetic carrier screening for reproductive purposes. How should it be continued?

Israel Journal of Health Policy Research ◽

10.1186/s13584-019-0345-1 ◽

2019 ◽

Vol 8 (1) ◽

Cited By ~ 1

Author(s):

Joël Zlotogora

Keyword(s):

Genetic Screening ◽

Screening Program ◽

Severe Disease ◽

Carrier Screening ◽

Specific Population ◽

Arab Population ◽

Live Births ◽

Israeli Population ◽

Population Program ◽

Genetic Carrier Screening

AbstractThe Israeli population genetic screening program for reproductive purposes, is a population-specific screening that includes all known, severe diseases and relatively frequent in a specific population (carrier frequency at or above 1:60 and/or disease frequency at or above 1 in 15,000 live births). The carrier screening program is free of charge and offers testing according to disease frequency in the different groups within the population.The extraordinary technical changes that occurred in the last decade as well as the changes in the type of marriages within the Israeli population necessitate a revision in the basis of the program.The screening should include instead of only the relatively frequent variants, all the variants that were reported among patients causing a severe disease for which the natural history is well known without regard of their frequency. The population-specific screening that determine which variants are included according to the origin of the couple should be abandoned for a general screening including either all the Jewish population or all the Israeli Arab population.

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A universal mid-trimester transvaginal cervical length screening program and its associated reduced preterm birth rate

American Journal of Obstetrics and Gynecology ◽

10.1016/j.ajog.2015.12.020 ◽

2016 ◽

Vol 214 (3) ◽

pp. 365.e1-365.e5 ◽

Cited By ~ 46

Author(s):

Moeun Son ◽

William A. Grobman ◽

Nina K. Ayala ◽

Emily S. Miller

Keyword(s):

Preterm Birth ◽

Birth Rate ◽

Screening Program ◽

Cervical Length ◽

Preterm Birth Rate

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A targeted population carrier screening program for severe and frequent genetic diseases in Israel

European Journal of Human Genetics ◽

10.1038/ejhg.2008.241 ◽

2008 ◽

Vol 17 (5) ◽

pp. 591-597 ◽

Cited By ~ 37

Author(s):

Joël Zlotogora ◽

Rivka Carmi ◽

Boaz Lev ◽

Stavit A Shalev

Keyword(s):

Screening Program ◽

Genetic Diseases ◽

Carrier Screening

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Causes of Birth of More Than One Thalassemia Major Patient in Families in South-east of Iran: Lessons for Prevention Programs

Health Scope ◽

10.5812/jhealthscope.116634 ◽

2021 ◽

Vol 10 (3) ◽

Author(s):

Ghasem Miri-Aliabad ◽

Seyed Mohammad Nasiraldin Tabatabaei ◽

Zahra Vaezi ◽

Afshin Amini ◽

Leila Asgarzadeh

Keyword(s):

Screening Program ◽

Demographic Data ◽

Genetic Diseases ◽

Parental Knowledge ◽

Thalassemia Major ◽

Cross Sectional Study ◽

Screening Tests ◽

Beta Thalassemia ◽

Cross Sectional ◽

Thalassemia Minor

Background: Beta-thalassemia major (TM) is one of the most common genetic diseases in Iran. Despite some efforts to reduce the incidence of TM, its incidence is still relatively high in some areas of the country. Methods: This cross-sectional study was performed on 635 families who had children with TM. The families that had more than one child with TM were enrolled. A demographic data questionnaire and a checklist containing queries about the reasons for the birth of the second or subsequent TM children were completed by each family. Finally, the data were analyzed using SPSS version 16. Results: Among the families that had more than one child with TM, 90, 23, and three families had two, three, and four children with the disease, respectively. Of the 261 patients studied, 125 (47.9%) and 136 (52.1%) had been born prior and after the implementation of the pre-marital screening program for beta-thalassemia in Iran, respectively. Also, in 29.4% of these families, parents were unaware of having thalassemia minor. In other cases, factors such as lack of knowledge about screening tests (14.0%), lack of financial compliance (13.2%), late referral for genetic tests (11.8%), and not undergoing screening tests despite recommendations (9.6%) were among the reasons declared by the families. In addition to these, religious and cultural reasons should also be mentioned as effective factors. Conclusions: This study showed that in only about 30% of the studied families, the parents were unaware of having thalassemia minor, and in other families, miscellaneous reasons were involved in the birth of the second or subsequent child with TM. In some cases, despite sufficient parental knowledge about the possibility of giving birth to a child with TM, no action was taken to prevent this event.

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Modeling Future Blood Requirements in Patients with Transfusion-Dependent β-Thalassemia in Greece

Blood ◽

10.1182/blood-2021-145860 ◽

2021 ◽

Vol 138 (Supplement 1) ◽

pp. 2984-2984

Author(s):

Kyriakos Souliotis ◽

Christina Golna ◽

Ilias Gountas ◽

Maria Tsironi

Keyword(s):

Patient Population ◽

Conflicts Of Interest ◽

Screening Program ◽

Reduction Rate ◽

Target Population ◽

Thalassemia Major ◽

National Registry ◽

Annual Reduction ◽

Incident Cases ◽

Related Mortality

Abstract Introduction : In Greece, official data confirm that blood supply is consistently declining, primarily because of decreased voluntary blood donations. At this rate, it is unclear whether there will be sufficient red blood cell (RBC) units to meet future demand for patients with β-thalassemia. We modeled future blood demand in patients with transfusion-dependent β-thalassemia (TDT) over the next 15 years to assess whether such a demand can be met. Methods: A discrete time, stochastic, individual-based model, was developed to assess future blood needs of patients with TDT in Greece. The model adopted a cohort approach and patients enter the model shortly after birth and exit at death. The model was seeded with data from the National Registry for Hemoglobinopathies in Greece (NRHG; patient population) and data from the National Blood Centre (RBC units) (Table). To quantify the decrease in TDT incidence, a linear regression model was fitted to the incident cases as described by Voskaridou (Voskaridou E, et al. Ann Hematol 2019;98:55-66). The calculated annual reduction rate was then applied to the observed thalassemia major (TM) and thalassemia intermedia (TI) incident cases for 2012 (Voskaridou E, et al. Ann Hematol 2012;91:1451-1458). The model assumes the reduction would continue through to 2020, from which time the incidence curve would be constant. Results: The model estimates a decrease in both target population, primarily due to the implementation of the national prenatal screening program and TM related mortality, (9.2%, 18.6%, and 26.0% in 2025, 2030, and 2034, respectively) and in demand for RBC units (100,665, 89,428 and 80,565, respectively) over the next 15 years. After accounting for any blood donated, based on latest (2017) data as projected to 2020, Greece is expected to be short of 56,716 RBC units to meet needs of patients with TDT in 2020. By 2025, 2030, and 2034, cumulative required RBC units for patients with TDT are estimated to be 307,150, 501,698, and 617,074, respectively. Assuming RBC units are divided among patients ≥ 18 years and those < 18 years in line with the population mix in the NRHG, cumulative RBC units required for adult patients with TDT are estimated to be 292,837, 464,337, and 554,083 by 2025, 2030, and 2034, respectively. Conclusions: Though blood demand for patients with TDT is expected to decrease in line with a decrease in the patient population, it will remain a challenge for the healthcare system in Greece to meet the demand, primarily due to a continuing shortage of available RBC units from voluntary donations. This annual deficit is estimated to accumulate to over 600,000 units over the next 15 years. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

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Thalassemia carrier detection among pregnant women

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2021.003 ◽

2020 ◽

Vol 13 (1) ◽

pp. e2021003

Author(s):

Edhyana Sahiratmadja ◽

Merry M.V. Seu ◽

Ita M. Nainggolan ◽

Johanes C. Mose ◽

Ramdan Panigoro

Keyword(s):

Pregnant Women ◽

Dna Analysis ◽

Screening Program ◽

Thalassemia Major ◽

Erythrocyte Indices ◽

Low Resource ◽

Resource Setting ◽

Low Resource Setting ◽

Different Genetic Background ◽

Catastrophic Disease

Thalassemia major becomes the fifth catastrophic disease in Indonesia, however, national wide screening program is not mandatory. This study aimed to re-assess the validity of the various erythrocyte indices in determining ?-thalalssemia carrier among pregnant women in a low resource setting area. An analytic study was performed, comparing conventional cut-off various erythrocyte indices with new modified cut-offs by Kumar et al. The concordance analysis was calculated with Mentzer Index (MI) as reference. The validity of erythrocyte indices against hemoglobin (Hb) A2 were analysed, confirmed by molecular examination for ?- and common ?-Globin South East Asia population. Of 102 pregnant women, 34% was still anemic after completion of 90 iron pills. The concordance of conventional cut-off Shine & Lal index (<1530) was none to slight in agreement (kappa 0.097) to conventional cut-off MI (<13). The concordance of SLI increased significantly to substantial agreement when both used modified cut-offs (kappa 0.729). However, both SLI and MI had missed most of HbE carriers and ?-thalassemia carriers which seemed to be prevalent in this population as shown by DNA examination. In contrary, simple MCV<80fl and MCH<27pg had covered those carriers. This is the first study from Nusa Tenggara Timur, a low resource area in Indonesia in attempt to mass screen thalassemia carriers in this area where a simple MCV<80 fL and MCH<27pg have been used for preliminary screening rather than other indices. Since the population in eastern part of Indonesia has different genetic background compared to the west, DNA analysis is of great interest to map the spectrum of globin mutations.

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