Premarital hemoglobinopathy screening program results of a province in the Black Sea region of Turkey: three years' experience.

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 ß-thalassemia (ß-thal) trait was 1.37% (n = 676), the frequency of the abnormal HbS was 0.04% (n = 20). The frequency of ß-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 ß-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.

Public awareness and attitude toward premarital screening program in Jazan region, Saudi Arabia, an endemic area for hemoglobinopathies: A cross-sectional study.

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.

Les hémoglobinopathies sont très répandues en Arabie saoudite, avec des taux d'incidence variables selon les régions. Les régions de l'Est et de Jazan ont les taux d'incidence les plus élevés. Pour prévenir les hémoglobinopathies, le programme de dépistage prénuptial (PMS) a été mis en place en Arabie saoudite pour identifier les couples à risque avant le mariage. Cette étude descriptive transversale visait à évaluer la sensibilisation et l'attitude des jeunes adultes envers le SPM à Jazan, en Arabie Saoudite, qui a impliqué 875 individus (560 hommes et 315 femmes). La présente étude rapporte une association significative entre le sexe, les antécédents personnels et familiaux de maladie et l'attitude envers le SPM chez les jeunes adultes (P < 0,05). L'étude conclut que bien qu'il existe un niveau substantiel de sensibilisation et d'attitude positive envers le SPM parmi la population, il est nécessaire de mener des campagnes de santé plus détaillées menées par les prestataires de soins de santé, les dirigeants et les dirigeants islamiques pour souligner l'importance du SPM en tant que mesure préventive. réduire l'incidence des hémoglobinopathies en Jazan, Arabie saoudite.

Thalassemia Status in Cambodia.

The population of Cambodia (in 2019) was approximately 16 million with an annual growth rate of 1.4% in which the prevalence of hemoglobinopathies was estimated at about 40.0% (range 30.0-50.0%) to be carriers, and 2240 annual births for ß-thalassemia major (ß-TM). The overall prevalence of ß-thalassemia (ß-thal) and α-thalassemia (α-thal) were 40.9 and 39.6%, respectively. Currently, the specific epidemiological data regarding the abnormal gene frequency/mutations among different ethnic groups is unknown. In 2011, national guidelines for the Clinical Management of Patients with Thalassemia in Cambodia were developed and published by the Ministry of Health (MoH). Packed red cells (PRCs) are available at most referral hospitals (provincial hospitals). Oral iron chelators [deferiprone (DFP) and deferasirox (DFX)] are only available from a private pharmaceutical company. The future needs for Cambodia are to develop a national policy on the prevention or control of ß-thal and α-thal, and a national registry of patients with thalassemia, to determine the gene frequency of α- and ß-thal in different regions of the country, and to place the iron chelators on the list of essential medicines.

ß-Thalassemia in Iran: Things Everyone Needs to Know About This Disease.

Iran, as a country located in the Thalassemia Belt, has made great progress in thalassemia prevention and treatment. The thalassemia prevention program was implemented in 1995 and the country-wide thalassemia treatment network, consisting of 64 medical universities and faculties, is active. The acknowledgment of the status of thalassemia treatment and prevention in Iran can be of significance to researchers of the countries affected with thalassemia. In the present research, the database of the Treatment Deputy Office of the Ministry of Health, Treatment and Medical Education and that of the Hemovigilance Network of the Iranian Blood Transfusion Organization, were used. The data were analyzed using the Statistical Package of the Social Sciences, version 23. The findings show 90.13% reduction in the expected cases of new ß-thalassemia (ß-thal) births in 2015. Moreover, out of 18,983 hemoglobinopathy patients, 17,342 are ß-thal major (ß-TM) and ß-thal intermedia (ß-TI) patients covered by 198 medical centers. Out of the total number of blood donations in Iran, 19.17% are allocated to thalassemia treatment. Iran has reached an acceptable level of success in thalassemia prevention and the preparation of safe and adequate blood. Iran's achievements can be adapted to other developing countries, particularly in the Middle East.

Current challenges in the management of patients with sickle cell disease - A report of the Italian experience.

Sickle cell disease (SCD) is an inherited red blood cell disorder caused by a structural abnormality of hemoglobin called sickle hemoglobin (HbS). Clinical manifestations of SCD are mainly characterized by chronic hemolysis and acute vaso-occlusive crisis, which are responsible for severe acute and chronic organ damage. SCD is widespread in sub-Saharan Africa, in the Middle East, Indian subcontinent, and some Mediterranean regions. With voluntary population migrations, people harboring the HbS gene have spread globally. In 2006, the World Health Organization recognized hemoglobinopathies, including SCD, as a global public health problem and urged national health systems worldwide to design and establish programs for the prevention and management of SCD. Herein we describe the historical experience of the network of hemoglobinopathy centers and their approach to SCD in Italy, a country where hemoglobinopathies have a high prevalence and where SCD, associated with different genotypes including ß-thalassemia, is present in the native population.

Trasplante de progenitores hematopoyéticos en niños con ß-talasemia y enfermedad drepanocítica: experiencia del grupo GETMON / Hematopoietic stem cell transplantation in pediatric patients with thalassemia and sickle cell disease: An experience of the Spanish Working Group for Bone Marrow Transplantation in Children (GETMON)

Antecedentes y objetivos: El incremento descrito en la prevalencia de hemoglobinopatías, de ß-talasemia mayor (TM) y de enfermedad drepanocítica (ED) que ha ocurrido en las últimas dos décadas en nuestro país ha generado nuevas necesidades en cuanto a recursos médicos tanto para la prevención como para el tratamiento de estos pacientes. El trasplante alogénico de progenitores hematopoyéticos (alo-TPH) es el tratamiento curativo disponible en nuestro medio para pacientes con hemoglobinopatías graves. El objetivo principal de este estudio fue conocer los resultados del alo-TPH en pacientes pediátricos con TM o ED realizados en unidades de trasplante hematopoyético pediátrico incluidas dentro del Grupo Español de Trasplante de Médula Ósea en Niños (GETMON). Material y métodos: Revisión retrospectiva de los pacientes sometidos a TPH en unidades de TPH del GETMON hasta el año 2015. Resultados: Se analizaron un total de 65 pacientes (43 pacientes afectados de TM y 22 de ED) que recibieron el alo-TPH en 6 unidades GETMON entre noviembre de 1989 y diciembre de 2014. La supervivencia libre de eventos 3años postrasplante fue del 81% y la supervivencia global del 92% en pacientes con TM. La supervivencia libre de eventos 3años postrasplante fue del 79% y la supervivencia global del 85% en pacientes con ED. Conclusiones: Los resultados de esta serie son comparables a los resultados de otras series internacionales y ofrecen un punto de partida para continuar intentando mejorar la evolución de estos pacientes

Background and objectives: A recently occurring increase of the prevalence of haemoglobinopathies, ß-thalassaemia major (TM) and sickle cell disease (SCD) over the last two decades in our country has generated new needs in terms of medical resources for both prevention and treatment of these patients. Allogeneic haematopoietic stem cell transplant (allo-HSCT) is a curative treatment available for patients who have severe haemoglobinopathies. The main objective of this study was to evaluate the results of allo-HSCT in paediatric patients with TM or SCD performed in paediatric hematopoietic transplant units within the Spanish Group of Bone Marrow Transplantation in Children (GETMON). Material and methods: Retrospective review of patients undergoing HSCT in the GETMON units until 2015. Results: A total of 65 patients were analysed (43 patients were affected with TM and 22 with SCD), who received allo-HSCT in 6 GETMON units between November 1989 and December 2014. Event-free survival three years post-transplant was 81% and overall survival 92% in patients with TM. Event-free survival three years post-transplant was 79% and overall survival 85% in patients with SCD. Conclusions: The results of this series are comparable to the results of other international series and offer a platform from which to continue trying to improve the evolution of these patients

Inherited blood disorders, genetic risk and global public health: framing 'birth defects' as preventable in India.

This paper engages critically with the global assemblage framing sickle cell and thalassaemia disorders as a 'global health crisis'; and the promise of genomics, largely DNA-based carrier/pre-conceptual screening, prenatal diagnosis with a view to terminations, deployed in framing a solution to these historically racialised spectrum of diseases as essentially preventable. Sickle cell and thalassaemia are recessively inherited, potentially life-threatening haemoglobin disorders with significant variation of severity, often needing life-long treatment. I argue that the re-classification of inherited blood disorders (IBDs) under 'prevention and management of birth defects' by the WHO in 2010 can be read as an ethical moment within the 'globalising turn' of IBDs and the use of genomics in addressing structural inequalities underpinning health in low- and middle-income countries. Using an Indian case study, the paper aims at first examining the language of risk through which genes and IBDs are mapped onto pre-existing populations (e.g. caste and tribe) as discrete, categories. Second, it discusses the likely social and ethical ramifications of classifying these recessive gene disorders as essentially preventable, despite cheaply available diagnostic tests and treatment options available in most countries in the South.

Pre-implantation genetic diagnosis.

The aim of pre-implantation genetic diagnosis (PGD) is to characterize the genetic status of the cells (usually single cells) that have been biopsied from oocytes/zygotes or embryos created in vitro during assisted reproductive treatment. PGD is a multi-step procedure that requires close collaboration between gynaecologists who are experts in assisted reproduction, embryologists who are experts in micromanipulation of germ cells and in embryo biopsy and geneticists who are experts in genetic analysis at the single-cell level. PGD can be applied as a form of early pre-natal diagnosis with the aim to establish a pregnancy unaffected by a haemoglobinopathy. In addition, PGD can identify embryos that are human leukocyte antigen compatible with an existing sibling affected by a haemoglobinopathy to support a haematopoietic stem cell transplantation. PGD has an advantage over conventional pre-natal diagnosis as it precludes the need to consider terminating an affected ongoing pregnancy. However, PGD is a multi-step, complex and costly procedure with an unpredictable outcome and thus is most suited for couples with an unsuccessful reproductive history or challenging reproductive status. In addition, PGD supports the cure of an affected child. Couples who decide to undergo a PGD cycle should be fully aware of the advantages and limitations. The three teams of health practitioners involved (gynaecologists, embryologists and geneticists) should thoroughly counsel the couples and provide support at all the stages: the initial evaluation of their genetic and reproductive status, all steps of assisted reproduction, embryo biopsy, genetic analysis and, when relevant, follow-up of pregnancy and baby(ies) delivered.

Molecular Epidemiology of Hemoglobinopathies in Cambodia.

Determining the magnitude of the thalassemia problem in a country is important for implementing a national prevention and control program. In order to acquire accurate thalassemia prevalence data, the gene frequency of α- and ß-thalassemia (α- and ß-thal) in different regions of a country should be determined. The molecular basis of thalassemia in Cambodia was performed by polymerase chain reaction (PCR)-based techniques in a community-based cross-sectional survey of 1631 unrelated individuals from three regions, Battambang, Preah Vihear and Phnom Penh. Thalassemia mutations were detected in 62.7% of the three studied population of Cambodia. Hb E (HBB: c.79G > A) was the most common ß-globin gene mutation with a frequency ranging from 0.139 to 0.331, while the most frequent α-globin gene mutation was the -α(3.7) (rightward) deletion (0.098-0.255). The other frequencies were 0.001-0.003 for ß-thal, 0.008-0.011 for α-thal-1 (- -(SEA)), 0.003-0.008 for α-thal-2 [-α(4.2) (leftward deletion)], 0.021-0.044 for Hb Constant Spring (Hb CS, HBA2: c.427T > C) and 0.009-0.036 for Hb Paksé (HBA2: c.429A > T). A regional specific thalassemia gene frequency was observed. Preah Vihear had the highest prevalence of Hb E (55.9%), α-thal-2 (24.0%) and nondeletional α-thal (15.1%), whereas Phnom Penh had the lowest frequency of thalassemia genes. Interestingly, in Preah Vihear, the frequency of Hb Paksé was extremely high (0.036), almost equivalent to that of Hb CS (0.044). Our results indicate the importance of micromapping and epidemiology studies of thalassemia, which will assist in establishing the national prevention and control program in Cambodia.

Population Screening and Prevention Strategies for Thalassemias and other Hemoglobinopathies of Eastern India: Experience of 18,166 cases.

We evaluated population screening programs (1999-2011), conducted by the Thalassaemia Foundation, Kolkata, India, for the first time in Eastern India in different districts of West Bengal, for prevention of thalassemia comprising screening of heterozygotes and ß-thalassemia intermedia (ß-TI) cases [ß(+), ß(++), ß(0)/ß(+), ß(E)/ß(E) (codon 26 or HBB: c.79G > A), Hb-E-ß-thalassemia (Hb E-ß-thal)]. Among 18,166 cases, we found 2092 heterozygotes and 2245 ß-TI individuals (who had no information about their disorders). Results were evaluated with standard hematological analyses including erythrocyte indices, hemoglobin (Hb) typing and quantification. Participants were divided into five groups (children, pre-marriage cases, pre-pregnancy cases, affected family members, pregnant women). The objectives of this evaluation were to fix cut-off values of red blood cells (RBCs), mean corpuscular volume (MCV), mean corpuscular Hb (MCH), red blood cell distribution width (RDW) and Hb A2, as the standard World Health Organization (WHO) guidelines were not strictly followed in mass-scale screening programs. We have observed many dilemmas in considering the status of the thalassemia subject, due to presence of some other clinical conditions such as iron deficiency anemia, α-thalassemia (α-thal), δ-thalassemia (δ-thal), clinically silent Hb variants, and some cases of non hemoglobinopathies (such as pregnancy) along with thalassemia. The MCV values varied greatly in different conditions of hemoglobinopathies, whereas MCH provided a more stable measurement. We found an MCH value of <27.0 pg is a suitable cut-off point for screening in this population. Participants with an MCH of <27.0 pg should be investigated further to confirm or exclude a diagnosis of ß-thal trait.

Premarital screening for hemoglobinopathies: experience of a single center in Kurdistan, Iraq.

BACKGROUND: A program for the prevention of major hemoglobinopathies was initiated in 2008 in the Kurdistan region of Iraq. This study reports on the achievements and challenges of the program. METHODS: A total of 102,554 individuals (51,277 couples) visiting a premarital center between 2008 and 2012 were screened for carrier status of hemoglobinopathies, and at-risk couples were counseled. RESULTS: A total of 223 (4.3/1,000) couples were identified and counseled as high-risk couples. Available data on 198 high-risk couples indicated that 90.4% proceeded with their marriage plans, and 15% of these married couples decided to have prenatal diagnosis (PND) in subsequent pregnancies with the identification of 8 affected fetuses; all were terminated as chosen by the parents. Thirty affected births were recorded among the high-risk couples. The premarital program managed to reduce the affected birth rate of major hemoglobinopathies by 21.1%. Of the 136 affected babies born during the study period, 77.9% were born to couples married prior to the start of the program, while 22.1% were born to couples identified as having a high risk. The main reason for not taking the option of PND was unaffordable costs. CONCLUSIONS: Financial support would have increased opting for PND by high-risk couples. Further reduction in affected birth rates could be achieved by including parallel antenatal screening programs to cover those married before the initiation of the premarital program and improving the public health education and counseling programs.

Haemoglobinopathies in Europe: health & migration policy perspectives.

BACKGROUND: Major haemoglobinopathies (MH), such as thalassaemia syndromes (Thal) and sickle cell disorders (SCD), are genetic defects associated with chronic anaemia and other complications. In Europe, MH are rare diseases (RD) but their prevalence is significantly growing in many countries due to mobility and migration flows. This creates a growing health problem in the EU that has not yet been effectively addressed by Member States (MS) authorities. The present study has been conducted with the aim of: (i) providing an overview of policies for MH in 10 EU member states (MS) (ii) analysing the challenges linked to these RD due to growing requirements imposed by population, mobility and migration trends and (iii) identifying gaps, proposing improvements on existing policies, or developing new ones to fit the identified needs. METHODS: The study has been undertaken by a group of members of the European Network for Rare and Congenital Anaemias (ENERCA) and the Thalassaemia International Federation (TIF), in collaboration with the public affairs firm Burson-Marsteller Brussels. Data from 10 EU countries have been gathered using targeted desk research and one-to-one interviews with local stakeholders, including healthcare professionals, patients and public health officers/providers. RESULTS: 1. MH are the most common RD in all the 10 countries, 2. Data on prevalence, overall burden, trends, and clinical follow up costs are lacking in most countries. 3. Neonatal screening practices show a wide variation across and within countries. 4. Awareness on MH and their related complications is very low, exception made of Italy, Greece, Cyprus and UK, 5. No disaggregated data is available to understand the impact of mobility and migration on the prevalence of haemoglobinopathies, and how healthcare delivery systems should adapt to respond to this situation. 6. Targeted policy measures and/or actions are generally lacking and/or delayed. CONCLUSIONS: Ten policy recommendations have been drawn from this study, building on 2006 WHO recommendations for MH to include haemoglobinopathies in National Plans of Actions for Rare Diseases.

Thalassemias and hemoglobinopathies in Turkey.

Thalassemias and hemoglobinopathies are a serious health problem in Turkey. There is a 70-year history of thalassemia in Turkey. The first patient with ß-thalassemia major (ß-TM) was reported in 1941. The first clinical and hematological studies were published by Aksoy in 1958. The overall incidence of ß-thalassemia (ß-thal) was reported by Çavdar and Arcasoy to be 2.1% in 1971. Important steps such as written regulations, education and prevention campaigns, have been taken to prevent thalassemia in Turkey by the Ministry of Health (MOH), the Turkish National Hemoglobinopathy Council (TNHC) and the Thalassemia Federation of Turkey (TFT) since 2000. A national hemoglobinopathy prevention program was started in provinces with a high prevalence by the MOH in 2003. While the percentage of premarital screening test was 30.0% of all couples in 2003, it reached 86.0% in 2013. While the number of newborn with thalassemias and hemoglobinopathies was 272 in 2002, it had dropped to 25 in 2010. There has been a 90.0% reduction of affected births in the last 10 years.

The first five years of a preventive programme for haemoglobinopathies in Northeastern Iraq.

OBJECTIVE: To evaluate the feasibility and effectiveness of a preventive programme for haemoglobinopathies in a single centre in Northeastern Iraq. METHODS: Premarital screening, genetic counselling and prenatal diagnosis (PND) were implemented over a 5 year period. RESULTS: Among a total of 108,264 screened individuals (54,132 couples), ß-thalassaemia trait, δß-thalassaemia trait, and sickle cell trait were diagnosed in 3.98%, 0.11% and 0.07%, respectively. Of 130 at risk couples (2.4/1000), 107 (82%) were available for follow up, with 105 couples (98.1%) proceeding with their marriage after counselling. In the 125 registered pregnancies in the latter couples, PND was performed in 85 (in 80 couples, uptake 76%). Selective termination was chosen in 10 of the 11 pregnancies with an affected fetus. Six affected babies were born among couples who declined PND. At the same time 30 already married couples with at least one thalassaemic child underwent PND, revealing three affected fetuses; all three pregnancies were terminated. CONCLUSION: The programme revealed that most at risk couples diagnosed by premarital screening chose to proceed with their marriage, with 76% seeking PND followed by selective termination of an affected fetus. A 65% reduction in number of affected births was reported over the 5 year period. This regional programme could serve as a prototype for a national haemoglobinopathy prevention programme.

Resultados del programa de prevención de hemoglobinopatías SS y SC / Results of the program to prevent hemoglobinopathies SS and SC

Las hemoglobinopatías, y dentro de ellas la sicklemia, constituyen las alteraciones monogénicas más frecuentes en el mundo, con un patrón de herencia autosómica recesiva; es alta su frecuencia en la población mundial. El Programa de Prevención de hemoglobinopatías se basa en el pesquisaje mediante el estudio de electroforesis de Hemoglobina a todas las gestantes. El objetivo fue analizar los resultados del programa de prevención de hemoglobinopatías en las áreas de salud del municipio Minas de Matahambre. Se realizó un estudio descriptivo, retrospectivo y de corte longitudinal al total de gestantes captadas desde el año 2005 al 2012 a las que se les realizó la electroforesis de hemoglobina, determinándose portadoras de alguna hemoglobina anormal, a estos casos se estudió la pareja, los resultados se presentaron mediante tablas y gráficos. La frecuencia de portadoras de hemoglobina S fue de 1,47 por ciento presentando mayor número el área de salud de Minas 2,1 por ciento, seguida de Santa Lucia y Sumidero con 1,3 por ciento y 0.8 por ciento respectivamente. La frecuencia de portadoras de hemoglobina C fue de 0,11 por ciento, el 95,3 por ciento de los esposos fueron estudiados y solo existió una pareja de riesgo a la cual se le propuso estudio molecular fetal. Se determinó la frecuencia de hemoglobina AS y AC en las gestantes, lo que posibilitará brindarles asesoramiento genético y estudio molecular fetal a las parejas de riesgo además se corroboró la necesidad de mejorar la educación de la población sobre la enfermedad(AU)

Hemoglobinopathies, among them sickle cell anemia, constitute the most frequent monogenic alterations all over the world, having an autosomal recessive inheritance pattern; showing a high frequency in worldwide population. The Program for the Prevention of Hemoglobinopathies is based on hemoglobin electrophoresis to all pregnant women.The objective was to examine the results of the Program for the Prevention of Hemoglobinopathies in the health areas of Minas de Matahambre municipality. A descriptive, retrospective and longitudinal study was carried out to the total of pregnant women recruited from 2005 to 2012, performing hemoglobin electrophoresis, determining the carriers of some abnormal hemoglobin, investigating the couple and these results were presented in tables and graphics. The frequency of hemoglobin SS carriers was 1, 47 per cent where the greatest number belonged to Minas health area 2,1 per cent, followed by Santa Lucia and Sumidero with 1,3 per cent and 0.8 per cent respectively. The frequency of hemoglobin C carriers was 0, 11 per cent and 95,3 per cent of the husbands were studied, only a couple carried the risk, to whom fetal molecular assessment was proposed. The frequency of hemoglobin AS and AC in pregnant women was determined, which will make possible to offer them genetic counseling and fetal molecular assessment to the couples at risk; besides it corroborated the need of improving the education of the population about the disease(AU)

Genetic epidemiology, hematological and clinical features of hemoglobinopathies in Iran.

There is large variation in the molecular genetics and clinical features of hemoglobinopathies in Iran. Studying structural variants of hemoglobin demonstrated that the ß-chain variants of hemoglobin S and D-Punjab are more prevalent in the Fars (southwestern Iran) and Kermanshah (western Iran) provinces, respectively. Also, α-chain variants of Hb Q-Iran and Hb Setif are prevalent in western Iran. The molecular basis and clinical severity of thalassemias are extremely heterogenous among Iranians due to the presence of multiethnic groups in the country. ß-Thalassemia is more prevalent in northern and southern Iran. Among 52 different ß-thalassemia mutations that have been identified among Iranian populations, IVSII-1 G:A is the most frequent mutation in most parts of the country. The presence of IVS I-5 G:C mutation with high frequency in southeastern Iran might reflect gene flow from neighboring countries. A wide spectrum of α-thalassemia alleles has been detected among Iranians with -α(3.7 kb) as the most prevalent α-thalassemia mutation. The prevention program of thalassemia birth in Iran has reduced the birth rate of homozygous ß-thalassemia since the implementation of the program in 1997. In this review genetic epidemiology, clinical and hematological aspects of hemoglobinopathies, and the prevention programs of ß-thalassemia in Iran will be discussed.

Thirty-year experience in preventing haemoglobinopathies in Greece: achievements and potentials for optimisation.

OBJECTIVES: Beta thalassaemia major (ß-TM) and sickle-cell disease (SCD) are severe haemogobinopathies requiring life-lasting, advanced medical management. In the Mediterranean region, both conditions occur with high frequency. We assessed the efficacy of the National Program for the Prevention of Haemoglobinopathies in Greece during the last 30 yrs. METHODS: Data of affected births between 01/01/1980 and 31/12/2009 were collected in a nationwide scale, and expected vs. observed rates of new births were calculated and compared. In a subpopulation of affected births of Greek origin, the causes for occurrence of the new affected birth were also collected and analysed. RESULTS: Overall, the reduction in new cases was 81.1% and 84.6% for ß-TM and SCD, respectively. For ß-TM, a constant declining trend was recorded over the 30-yr period, whereas for SCD, a transient reversal was observed in the mid-1990s probably due to the significant influx of immigrants of African origin. Programme failure was 2.2 times more common among new ß-TM births of Greek origin compared to new SCD cases (P < 0.001). Unawareness and parental choice were more frequent in SCD compared to ß-TM (unawareness: OR = 1.4, P = 0.05, parental choice: OR = 1.9, P = 0.01). The main cause for programme failure was carrier misidentification and incorrect genetic advice for ß-TM and SCD, respectively. CONCLUSIONS: The ß-TM and SCD prevention programme in Greece has significantly reduced the numbers of new affected births. The outcomes could be optimised in groups of non-Greek origin, in carrier identification and by offering specialised genetic counselling.

A proficiency testing program of hemoglobin analysis in prevention and control of severe hemoglobinopathies in Thailand.

BACKGROUND: No external quality assessment program for hemoglobin (Hb) analysis in the prevention and control of thalassemia has been established in Thailand. To improve the first line provisional diagnostics, the first proficiency testing (PT) program has been established. METHODS: External Hb controls prepared at our center were sent to Hb analysis laboratories all over the country. Three cycles per year were performed in 2010 and 2011. In each cycle, two control samples with corresponding hematological parameters, designated as husband and his pregnant wife were supplied for Hb analysis. Each member analyzed the control samples in their routine practices. The results of Hb analysis, laboratory interpretation and risk assessment of the expected fetus for severe thalassemia diseases targeted for prevention and control were entered into the report form and sent back to our center. Participants reports were analyzed and classified into four different quality groups; Excellent (when all the three parameters are correct), Good (correct Hb analysis and interpretation but incorrect risk assessment), Fair (correct Hb analysis but incorrect interpretation and risk assessment) and Needs improvement (incorrect Hb analysis). RESULTS: It was found that most participants could report correct Hb types and quantifications but some misinterpretations and risk assessments were noted. These were clearly seen when control samples with more complexity were supplied. CONCLUSIONS: These results indicate a further improvement is required in the laboratory interpretation and knowledge of the laboratory diagnosis of thalassemia. The established system should facilitate the prevention and control program of thalassemia in the region.

Immigration and changes in the epidemiology of hemoglobin disorders in Italy : an emerging public health burden.

BACKGROUND: In the last years Italy is confronting with massive migratory movements from developing countries where hemoglobinopathies are widespread. This is causing a large diffusion and a changing spectrum in the epidemiology of hemoglobin disorders in Italy. METHODS: Investigations recently published in Italy on hemoglobinopathies among immigrants were revised in order to appreciate the impact of immigration from developing countries on epidemiology of these pathologies and to outline adequate guidelines of prevention. RESULTS: Although in Italy there is a limited number of investigations regarding the relation between immigration and hemoglobin disorders, published data show that in our Nation there is a changing and increasing spectrum of hemoglobinopathies linked to immigration. CONCLUSIONS: Prospective and retrospective actions of public healthy preventive policy are requested, based upon information (health educational programs for immigrants and caregivers), screenings among immigrants (school screening, pre-marital, preconception and early pregnancy screening, newborn screening), counseling for foreign at-risk couples and healthy carriers.

A national registry of haemoglobinopathies in Greece: deducted demographics, trends in mortality and affected births.

Haemoglobinopathies are the most common hereditary disorders in Greece. Although there is a successful national prevention program, established 35 years ago, there is lack of an official registry and collection of epidemiological data for haemoglobinopathies. This paper reports the results of the first National Registry for Haemoglobinopathies in Greece (NRHG), recently organized by the Greek Society of Haematology. NRHG records all patients affected by thalassaemia major (TM), thalassaemia intermedia (TI), "H" Haemoglobinopathy (HH) and sickle cell disease (SCD). Moreover, data about the annual rate of new affected births along with deaths, between 2000 and 2010, are reported. A total of 4,506 patients are registered all over the country while the number of affected newborns was significantly decreased during the last 3 years. Main causes for still having affected births are: (1) lack of medical care due to financial reasons or low educational level; (2) unawareness of time limitations for prenatal diagnosis (PD); due either to obstetricians' malpractice or to delayed demand of medical care of couples at risk; and (3) religious, social or bioethical reasons. Cardiac and liver disorders consist main causes for deaths while life expectancy of patients lengthened after 2005 (p < 0.01). The NRHG of patients affected by haemoglobinopathies in Greece provides useful data about the haemoglobinopathies in the Greek population and confirms the efficacy of the National Thalassaemia Prevention Program on impressively decreasing the incidence of TM and sickle cell syndromes.