Sickle Cell Disease Carriers Research Articles

RETRACTION: [Carriers of sickle cell disease: reflections of the Black people history on access to the health

A Revista Eletrônica de Comunicação, Informação & Inovação em Saúde – Reciis comunica a publicação formal de retratação para extração do artigo: RAMOS, Edith Maria Barbosa; RAMOS, Paulo Roberto Barbosa; CARVALHO, Márcia Haydee Porto de; SILVA, Delmo Mattos da; DUTRA JÚNIOR, Paulo Henrique de Freitas. Portadores da doença falciforme: reflexos da história da população negra no acesso à saúde. Revista Eletrônica de Comunicação, Informação & Inovação em Saúde, Rio de Janeiro, v. 14, n. 3, p. 681-691, 2020. DOI: https://doi.org/10.29397/reciis.v14i3.1182. desde que foram identificadas inconformidades com a política editorial da revista. Christovam Barcellos Igor Sacramento Kizi Mendonça de Araújo Editores científicos

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.

Sickle cell disease (SCD) is a life-threatening disease requiring reliable early diagnosis. We assessed the acceptability and diagnostic performances of two rapid diagnostic tests (RDTs) to identify SCD (HbSS, HbSC, HbS/β-thalassaemia) or SCD carrier (HbS/HbC) in a pilot SCD newborn screening (NBS) strategy in Mali. All consenting delivering women were offered SCD NBS using cord blood sampling on two RDTs (SickleScan® and HemotypeSC®) compared to the high-performance liquid chromatography (HPLC) gold standard to detect SCD states. From April 2021 to August 2021, 4333 delivering women were eligible of whom 96.1% were offered NBS: 1.6% refused, 13.8% delivered before consenting and 84.6% consented; 3648 newborns were diagnosed by HPLC; 1.64% had SCD (0.63% HbSS, 0.85% HbSC, 0.16 HbS/β-plus-thalassaemia); 21.79% were SCD carrier. To detect accurately SCD, SickleScan® had a sensitivity of 81.67% (95% confidence interval [CI]: 71.88-91.46) and a negative predictive value (NPV) of 99.69% (95% CI: 99.51-99.87); HemotypeSC® had a sensitivity of 78.33% (95% CI: 67.91-88.76) and a NPV of 99.64% (95% CI: 99.44-99.83). To detect SCD carrier: SickleScan® sensitivity was 96.10% (95% CI: 94.75-97.45) and NPV, 98.90% (95% CI: 98.51-99.29); HemotypeSC® sensitivity was 95.22% (95% CI: 93.74-96.70) and NPV, 98.66% (95% CI: 98.24-99.03). Routine SCD NBS was acceptable. Compared with HPLC, both RDTs had reliable diagnostic performances to exclude SCD-free newborns and to identify SCD carriers to be further confirmed. This strategy could be implemented in large-scale NBS programmes.

Abstract 104: Cytochrome B5 Reductase 3 Regulates The Erythropoietin Response To Ischemic Stroke In A Mouse Model Of Chronic Anemia And Oxidative Stress

Introduction: Cytochrome b5 reductase 3 (Cyb5R3) is a heme iron reductase that reverses oxidized soluble guanylate cyclase (sGC) heme iron (Fe 3+ Fe 2+ ) to preserve nitric oxide signaling. Under oxidative stress, such as occurs with sickle cell disease (SCD) and ischemic stroke, Cyb5R3 redox signaling provides resilience against tissue damage. A loss-of-function (roughly 50%) Cyb5R3 missense variant (T117S) occurs with high frequency (0.23 minor allele) in persons of African ancestry, who also suffer a greater burden of sickle cell anemia and ischemic stroke than other races. We hypothesized that Cyb5R3 regulates the erythropoietin response to ischemic stroke in a mouse model of SCD. Methods: Age-matched male SCD mice with wild-type Cyb5R3 (SS WT ) or T117S Cyb5R3 (SS T117S ) underwent middle cerebral artery occlusion (55 min) and reperfusion (48 hr). Blood was sampled at baseline and 48h reperfusion for hematology measurements. Brains were stained with 2,3,5-triphenyltetrazolium chloride to quantify infarct volume. Erythropoietin (EPO), heme oxygenase 1 (HMOX1) and sGC were assayed by Western blot. Results: We found brain infarct volume to be greater in SS T117S vs SS WT (63 vs 27 cm 3 , respectively; P=0.003). Red cells, hematocrit and hemoglobin decreased in SS T117S post-stroke, which was opposite to SS WT (red cells: -13% vs 13%, P=0.01; hematocrit: -20% vs 0%, P=0.03; hemoglobin: -18% vs 3%, P=0.02, respectively). In the absence of stroke (age-matched controls), SS WT had elevated HMOX1 protein compared to SS T117S , which normalized in post-stroke SS WT but was unchanged in post-stroke SS T117S . Kidney and plasma EPO levels significantly increased in SS WT post-stroke, but not in SS T117S . In vitro studies using HEK293 cells showed EPO and HMOX1 decrease with Cyb5R3 knockdown by siRNA. Conclusion: Our findings suggest a modifying role for Cyb5R3 in brain-kidney crosstalk during ischemic stroke, wherein loss of T117S Cyb5R3 activity negatively impacts renal and plasma EPO levels and resilience against infarct of ischemic brain tissue. The Cyb5R3 axis on which the brain-kidney-blood response to stroke in SCD turns represents a novel target for precision medicine approaches to managing stroke risk and pathology in SCD carriers of the T117S variant.

Effect of ABO Mismatch and RBC Alloimmunization on the Outcomes of Patients with Sickle Cell Disease Undergoing Hematopoietic Stem Cell Transplantation

Background: Hematopoietic stem cell transplantation (HSCT) remains the only well-established curative option for sickle cell disease (SCD) patients. Non-myeloablative (NMA) conditioning has been used to improve the outcomes and reduce toxicities in adult SCD patients. However, Recipient/Donor (R/D) ABO incompatibility and alloimmunization could be significant impediments to successful outcomes when transplanting SCD patients due to risks of hemolysis, delayed engraftment, poor graft function and graft failure (GF). Herein, we report our experience with allogeneic HSCT for SCD and the effects of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. Methods: We conducted a retrospective analysis of all adolescents and adult SCD patients (age >14 year) that underwent HSCT from January 2015 to February 2022 at our center. All patients received Intravenous alemtuzumab (1 mg/kg divided over 5 days on days -7 to -3) and 300 cGy TBI on day -2 or -1 for conditioning. Pre-transplant preparation consisted of hydroxyurea at maximum tolerated dose for 2-3 months and one session of exchange transfusion. Peripherally mobilized stem cells targeting 10x106 /kg of CD34 cells were used. For graft versus host disease (GVHD) prophylaxis sirolimus was started on day -1 and continued for one year with tapering if lymphoid chimerism was > 50%. For Patients with major ABO incompatibility, we administered 2 doses of rituximab (375 mg/m2) and 3 sessions of plasmapheresis before starting the conditioning regimen targeting an isoheamagglutinin titer < 1/32. The primary objective was to determine the impact of RBC groups mismatch and alloimmunization on the outcome of transplanted patients. The secondary objective was to assess the impact of GF on overall survival (OS). Logistic regression was done to evaluate predictors for GF. Kaplan-Meier method was used for survival analysis. Results: A total of 194 patients were included with a median age of 26 years and 55.6% being males. The median baseline Hgb and HbS were 93 g/L and 71.3%, respectively. Indications of stem cell transplantations were most commonly due to recurrent vaso-occlusive crisis in 52.57% of patients, CNS disease in 19.58%, and acute chest syndrome in 17.01%. Other indications included sickle nephropathy, sickle hepatopathy, priapism and AVN in 10.82% of patients collectively. Around 59% of donors were sickle cell disease carriers, and 41% were healthy donors. After a median follow up of 28.8 months (5-83), sixteen patients (8%) experienced graft failure (3 with primary GF and 13 with secondary GF). On univariate analysis (table 1a), ABO minor incompatibility (odds ratio (OR), 3.63; 95% confidence interval (CI), 1.13 -11.65, P=0.029, and RBC alloantibodies against donor non-ABO antigens (OR, 4.22; 95% CI, 1.17 -15.14, P=0.039) were predictive for GF. However, on multivariate analysis (table 2a), only RBC alloantibodies against donor non-ABO antigens (OR, 8.29; 95% CI, 2.01 to 34.05, P=0.0033) was predictive of GF. None of the 16 patients with major ABO incompatibility developed GF. Two-years OS for all patients was 95%. The median OS for patients with GF was 98% compared to 74% patients without GF, P<0.0001) (Figure 1). Conclusion: In our SCD transplanted patients, RBC alloantibodies against donor non-ABO antigens was an independent risk factor for GF. Patients with GF had an inferior survival and strategies for decreasing the risks are needed. Figure 1View largeDownload PPTFigure 1View largeDownload PPT Close modal

Assessment of Factors Associated with the Effectiveness of Premarital Screening for Hemoglobinopathies in the South of Saudi Arabia.

PurposeSouthern region of Saudi Arabia has one of the highest prevalence of sickle cell disease and thalassemia in the kingdom. This study aims to assess the factors associated with the rejection of premarital clinical counselling in the Jazan region.MethodsThis is a cross-sectional investigation conducted in the Jazan region of Saudi Arabia. The investigation targeted subjects who performed premarital screening and, with their screened partners, were identified as high-risk couples and proceeded with their marriage. Data were collected via a web-based self-administered questionnaire. A section of the questionnaire targeted those who attended the premarital counselling clinic in the Jazan region and assessed the factors that led to the rejection of premarital counselling advice.ResultsA total of 413 participants were recruited. The mean age of the respondents was 33 years, and the majority of the respondents were female (62.5%). The majority of the respondents were related to their partners (66.8%) and were carriers of sickle cell disease (67.8%). Among the respondents, only 192 had attended premarital counselling clinics in the Jazan region. More than half of the attendees rejected the premarital counseling advice because they believed that their marriage was their unavoidable destiny. About 30% of the attendees reported that disease complications were not well explained during the counselling. Thirty-five attendees (18.2%) proceeded with the marriage because they thought the risk of transmitting the disease to their children was small and 10 attendees (5.2%) proceeded with their marriage because they believed their children’s lives would not be affected by the disease.ConclusionThe findings explain the limited influence of the premarital counselling advice in raising the awareness of the attendees about inherited blood disorders. The findings indicate a strong cultural influence leading to the reduced effectiveness of premarital counselling in the Jazan region.

College student’s attitudes about SCD carrier screening

ABSTRACT Sickle Cell Disease (SCD) is an inherited blood disorders that leads to several health problems ranging from delayed growths, recurrent infections, vision problems, chronic hemolysis, kidney disease to low quality of life and life expectancy. Beyond individuals and families, SCD has the potential of economically burdening communities and societies. A non-probability sampling approach using a convenience sample of college students was used for this study. Data were obtained through an online survey derived from a modified version of the Attitudes to Participation in Carrier Testing scale. Results indicated that overall participants had positive attitudes toward screening; however, only 26% knew their own carrier status highlighting the need for improved screening participation.

Levels of angiotensin-converting enzyme 1 and 2 in serum and urine of children with Sickle Cell Disease

Introduction:Sickle cell nephropathy begins in childhood and presents early increases in glomerular filtration, which, over the long term, can lead to chronic renal failure. Several diseases have increased circulating and urinary angiotensin-converting enzyme (ACE) activity, but there is little information about changes in ACEs activity in children with sickle cell disease (SCD).Objective:We examined circulating and urinary ACE 1 activity in children with SCD.Methods:This cross-sectional study compared children who were carriers of SCD with children who comprised a control group (CG). Serum and urinary activities of ACE were evaluated, as were biochemical factors, urinary album/creatinine rates, and estimated glomerular filtration rate.Results:Urinary ACE activity was significantly higher in patients with SCD than in healthy children (median 0.01; range 0.00-0.07 vs median 0.00; range 0.00-0.01 mU/mL·creatinine, p < 0.001. No significant difference in serum ACE activities between the SCD and CG groups was observed (median 32.25; range 16.2-59.3 vs median 40.9; range 18.0-53.4) mU/m`L·creatinine, p < 0.05.Conclusion:Our data revealed a high urinary ACE 1 activity, different than plasmatic level, in SCD patients suggesting a dissociation between the intrarenal and systemic RAAS. The increase of urinary ACE 1 activity in SCD patients suggests higher levels of Ang II with a predominance of classical RAAS axis, that can induce kidney damage.

Carriers of sickle cell disease: reflections of the Black people history on access to the health

A Revista Eletrônica de Comunicação, Informação &amp; Inovação em Saúde – Reciis comunica a publicação formal de retratação para extração do artigo: RAMOS, Edith Maria Barbosa; RAMOS, Paulo Roberto Barbosa; CARVALHO, Márcia Haydee Porto de; SILVA, Delmo Mattos da; DUTRA JÚNIOR, Paulo Henrique de Freitas. Portadores da doença falciforme: reflexos da história da população negra no acesso à saúde. Revista Eletrônica de Comunicação, Informação &amp; Inovação em Saúde, Rio de Janeiro, v. 14, n. 3, p. 681-691, 2020. DOI: https://doi.org/10.29397/reciis.v14i3.1182. desde que foram identificadas inconformidades com a política editorial da revista. Christovam Barcellos Igor Sacramento Kizi Mendonça de Araújo Editores científicos Retratação do artigo: https://www.reciis.icict.fiocruz.br/index.php/reciis/article/view/4118/version/2737

An Evaluation of Three Ways of Communicating Carrier Status Results to the Parents of Children in a Neonatal Sickle Cell Screening Programme.

Aim: Sickle cell disease (SCD) is the most frequent monogenic disease worldwide; ~5–7% of the world population carry a hemoglobin disorder trait. In the US, one in every 1,941 newborns has SCD, whereas one in every 3,000 newborns in France is affected - resulting in 385 new cases and 5,883 newly identified carriers per year. The objective of the present study was to evaluate three different ways of providing information to parents at risk of having a child with SCD, with a view to increasing the parental screening rate and decreasing the number of new cases per year in France.Method: In a randomized study, we contacted 300 couples of parents after their child had been identified as a SCD carrier in the French national newborn screening programme: 100 couples received an information letter (the standard procedure in France: arm A), 100 couples received a letter and then a follow-up phone call (arm B), and 100 received a letter and then three follow-up text messages at 5-day intervals (arm C). The primary endpoint was the number of parents in each arm screened in the 120 days after the letter had been sent. In a modified intention-to-treat analysis, the screening rate was 17% in arm A, 35% in arm B, and 30% in arm C.Results: Telephone and text message follow-ups were associated with higher screening rates, compared with no follow-up. After being informed of their child's carrier status, some parents had consulted a healthcare professional but had not been referred for screening (16% in arm A, 19% in arm B, and 13% in arm C).Conclusion: A letter followed by a phone call or three text messages is more effective than a letter alone for informing parents at risk of having a child with SCD. The effective implementation of this follow-up programme probably requires better training of all the healthcare professionals involved.

A novel non-invasive prenatal sickle cell disease test for all at-risk pregnancies.

Sickle cell disease (SCD) is the most common genetic haematological disorder. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived procedure-related miscarriage risk. We report the development of a targeted massively parallel sequencing (MPS) assay for the NIPD of fetal SCD using fetal cell-free (cf)DNA from maternal plasma, with no requirement for paternal or proband samples. In all, 64 plasma samples from pregnant women were analysed: 42 from SCD carriers, 15 from women with homozygous (Hb SS) SCD and seven from women with compound heterozygous (Hb SC) SCD. Our assay incorporated a relative mutation dosage assay for maternal carriers and a wild type allele detection assay for affected women (Hb SS/Hb SC). Selective analysis of only smaller cfDNA fragments and modifications to DNA fragment hybridisation capture improved diagnostic accuracy. Clinical sensitivity was 100% and clinical specificity was 100%. One sample with a fetal fraction of <4% was correctly called as 'unaffected', but with a discordant genotype (Hb AA rather than Hb AS). Six samples gave inconclusive results, of which two had a fetal fraction of <4%. This study demonstrates that NIPD for SCD is approaching clinical utility.

Non-Invasive Prenatal Diagnosis (NIPD) of Sickle-Cell Disease By Massively Parallel Sequencing of Cell-Free Fetal DNA in Maternal Serum

Sickle cell disease (SCD) is the most common genetic haematological disorder worldwide. Around 300.000 affected infants are born every year, including at least 1000 in the United States. Prenatal diagnosis is currently carried out using amniotic fluid or chorionic villus sampling. These invasive procedures are perceived to have a small risk of miscarriage. The availability of non-invasive prenatal diagnosis (NIPD) is predicted to increase uptake of prenatal diagnosis for SCD, as it has no perceived miscarriage risk. NIPD may also be more readily implemented than invasive prenatal diagnosis in the low-resource countries in which SCD is the most prevalent. However, accurate NIPD of autosomal recessive disorders such as sickle cell disease has proven challenging as this requires detection of fetal inheritance of a maternal allele from a mixed maternal-fetal pool of cell-free DNA. We report the development of a targeted massively parallel sequencing assay for the NIPD of fetal SCD using cell-free fetal DNA from maternal plasma. No paternal or previous offspring samples were required. 44 clinical samples were analysed, including 37 plasma samples from pregnant SCD carriers and 7 plasma samples from women with SCD due to Hb SC. We used a relative mutation dosage based approach for the 37 samples from maternal SCD carriers (Hb AS or Hb AC), integrating Unique Molecular Identifiers (UMIs) into the analysis to improve the accuracy of wildtype and mutant allele counts. We used a separate wildtype allele detection approach for the 7 samples from women with compound heterozygous SCD, in whom the detection of wildtype cell-free DNA indicates the presence of a carrier fetus. The success of the assay was evaluated by comparing results with the established fetal sickle status as determined through either invasive prenatal diagnosis or newborn screening. During development, two key factors improved the accuracy of the results: i) Selective analysis of only smaller cell-free DNA fragments enhanced the fetal fraction for all samples, with greater effects observed in samples from earlier gestations. This approach improved diagnostic accuracy: for 3 out of 44 samples, the genotype was inconclusive or incorrect before size selection, but correct after size selection. ii) Modifications to DNA fragment hybridisation capture optimised the diversity of Unique Molecular Identifier-tagged molecules analysed. This led to improvements in the results obtained for 5 samples, with 3 previously inconclusive samples correctly called and 2 previously discrepant results moved into the inconclusive range. In total, 37 results were concordant with the established fetal sickle status; this included 30/37 samples from carrier women and 7/7 samples from women with sickle cell disease due to Hb SC. The remaining 7 carrier samples gave an inconclusive result, which for 3 samples was attributed to a low fetal fraction. Samples from as early as 8 weeks gestation were successfully genotyped. There were no false positive or false negative results. This study is the largest to use NGS-based NIPD on clinical plasma samples from pregnancies at risk of SCD. Efforts to validate the assay on a larger sample cohort and to reduce the inconclusive rate are warranted. This study shows that NIPD for SCD is approaching clinical utility and has the potential to provide increased choice to women with pregnancies at risk of sickle cell disease. Disclosures Silcock: Nonacus Ltd.: Employment.

Sickle cell disease in Western Nepal

Introduction: Since 2003, only few cases of sickle cell disease have officially been reported in Nepalese medical journals, and all reported patients belong to the Tharu ethnic group of Nepal. This is the first study that details sickle cell disease and carrier in 1250 individuals in western Nepal.&#x0D; Methods: This is a retrospective review of the patients and carriers of sickle cell disease diagnosed by either a positive haemoglobin electrophoresis report or a positive high performance liquid chromatography (HPLC) report. Analysis was done using SPSS 20.&#x0D; Results: Out of the 1250 individuals, 51.4% were females. 601 (48.08%) were patients with a form of sickle cell disease, the mean age was 24.5  12 yrs years. Most patients came from Bardiya district. Most common symptoms were related to joint pain. The patients and carriers of sickle cell disease were mostly from Tharu ethnic group (97.7%).&#x0D; Conclusion: These data suggest that sickle cell disease and other haemoglobinopathies are more prevalent than previously reported among members of the Tharu ethnic group and other residents of western Nepal. More research is imperative to assess the burden of the sickle cell disease and other haemoglobinopathies in Nepal.

Premarital screening of college students for carrier detection in thalassemia and sickle cell disease: need of the hour

Background: Hemoglobinopathies are a group of inherited conditions characterized by quantitative and qualitative abnormalities in the synthesis of hemoglobin. In India, the most prevalent hemoglobinopathies are thalassemia and sickle cell anemia. To reduce the burden of highly prevalent monogenic disorders, it is essential that disease progression be halted at the carrier stage. This can be done by carrier detection and genetic counseling in young individuals. In Central India, where prevalence of thalassemia and sickle cell anemia is high, premarital screening is being implemented for the first time in medical students for identification of asymptomatic carriers of these hemoglobinopathies and possible prevention of future high-risk marriages by genetic counseling. Objectives: The objectives of this study were to (1) determine the prevalence of asymptomatic carriers of sickle cell disease and thalassemia in first-year MBBS students; and (2) know the frequency of hemoglobinopathy carriers in different ethnic groups of this study group. Materials and Methods: This study was conducted at a Regional Hemoglobinopathy Detection and Management Centre of a tertiary-care hospital in central India in newly admitted medical students and was approved by the institutional ethics committee. Venous blood samples were analyzed for blood counts and solubility test positivity. Electrophoresis for pattern analysis and high-performance liquid chromatography for confirmation of diagnosis were used on each student. Results were analyzed with the help of statistical analysis. Results: Overall prevalence of hemoglobinopathies was 10%. Beta-Thalassemia trait was the most prevalent hemoglobinopathy followed by sickle cell trait. Presence of hemoglobinopathies was seen in varied ethnic groups. Conclusion: Importance of screening in young asymptomatic individuals is highlighted.

Newborn Blood Spot Screening for Sickle Cell Disease by Using Tandem Mass Spectrometry: Implementation of a Protocol to Identify Only the Disease States of Sickle Cell Disease

The currently recommended technologies of HPLC and isoelectric focusing for newborn blood spot screening for sickle cell disease (SCD) identify both the disease and carrier states, resulting in large numbers of infants being followed up unnecessarily. Analysis of blood spot tryptic peptides performed by using tandem mass spectrometry (MS/MS) is an alternative technology to detect hemoglobin (Hb) variant disorders. We analyzed 2154 residual newborn blood spots and 675 newborn blood spots from infants with Hb variants by using MS/MS after trypsin digestion. Screening cutoffs were developed by using the ratio between the variant peptide-to-wild-type peptide abundance for HbS, C, D(Punjab), O(Arab), Lepore, and E peptides. A postanalytical data analysis protocol was developed using these cutoffs to detect only the disease states of SCD and not to identify carrier states. A parallel study of 13 249 newborn blood spots from a high-prevalence SCD area were analyzed by both MS/MS and HPLC. Screening cutoffs developed distinguished the infants with the disease states of SCD, infants who were carriers of SCD, and infants with normal Hb. In the parallel study no false-negative results were identified, and all clinically relevant cases were correctly identified using the MS/MS protocol. Unblinding the data revealed a total of 328 carrier infants that were successfully excluded by the protocol. The screening protocol developed correctly identified infants with the disease states of SCD. Furthermore, large numbers of sickle cell carrier infants were successfully not identified, thereby avoiding unnecessary follow-up testing and referral for genetic counseling.

Zinc supplements for treating thalassaemia and sickle cell disease.

Zinc supplements for treating thalassaemia and sickle cell disease.

Research in athletes with sickle cell trait: just do it

the sickle cell trait (SCT) genotype, a condition found in an estimated 300 million people worldwide and 8–9% of African Americans is characterized by the heterozygous inheritance of a single defective beta globin gene. Inherited in the homozygous form, the beta globin gene mutation leads to

Phenotype and Genotype Frequency of β-Thalassemia and Sickle Cell Disease Carriers in Halkidiki, Northern Greece

A decade of screening (years 2000 to 2010) for hemoglobinopathies in 3,931 patients was performed at the General Hospital of Poligiros, Halkidiki, Northern Greece. Among the patients examined, 10.8% heterozygotes for β-thalassemia (β-thal) were found, as well as 4.1% with sickle cell disease and 1.2% with double β-thal/Hb S [β6(A3)Glu→Val] heterozygosity. Iron deficiency was observed in 23.4%.The geographical distribution in the region revealed a substantial incidence of hemoglobinopathies even in mountainous areas. This pattern did not follow the typical distribution according to the malaria hypothesis, as incidence did not dovetail with swamp locations recorded in the past.The HBB gene mutations for 85 patients were also analyzed. Most prevalent in Halkidiki, Northern Greece, was the codon 39 (C>T) mutation (27.1%) followed by the IVS-I-110 (G>A) mutation (22.4%); this was in direct contrast to the current distribution of the same mutations seen in the rest of Greece (Greek National Genetic Database, GNGD). This frequency inversion was statistically significant, with the difference from the GNGD being 20.6% for the IVS-I-110 mutation (p <0.0005) and 7.6% for the codon 39 mutation (p = 0.0238). The history of Halkidiki, denoting a clear example of geographical isolation from the rest of the country, may possibly account for a potentially diverse genetical identity of the disease in this region.

Providing Genetic Risk Information to Parents of Newborns with Sickle Cell Trait: Role of the General Practitioner in Neonatal Screening

In 2007, the neonatal screening program in the Netherlands was expanded to include hemoglobinopathies. Newborns with sickle cell disease (SCD), as well as SCD carriers are identified. The benefit of reporting SCD carriers includes detection of more couples at risk (both parents are carriers) who can be informed about future reproductive choices, a responsibility of their general practitioner (GP). We evaluated knowledge, ideas, and actions of GPs after reporting SCD carriers and explored and analyzed potential barriers. A questionnaire study. A total of 139 GPs responded to our questionnaire (49%). Ninety GPs (90%) stated they informed parents of the test result. In only 23 cases (23%) both parents had themselves tested for hemoglobinopathies. Eighty-one GPs (64%) stated that they did not have enough clinical experience with SCD. Almost half of the GPs indicated that they did not experience any barriers in counseling patients (n=60, 48%). At the moment, the goal of the neonatal screening for SCD carriers has not been achieved as the majority of parents were not tested for hemoglobinopathies after disclosure of carrier status in their newborn. With GPs reporting few barriers in counseling parents and only indicating a lack of knowledge and clinical experience, more effort is required to provide better information to GPs to help facilitate their work.

Counterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity

Counterpoint: Sickle cell trait should not be considered asymptomatic and as a benign condition during physical activity

Point:Counterpoint: Sickle cell trait should/should not be considered asymptomatic and as a benign condition during physical activity

Sickle cell trait (SCT) is found in ∼8% of African Americans and may be found in up to 40% of West Africans. However, most of them are unaware of their status. This observation suggests that SCT may be asymptomatic and remains a benign condition for daily life activities ([5][1]). Indeed, numerous