Β-thalassemia Carriers Research Articles

Screening of β-thalassemia carriers in high school students in Shebin El-Kom, Menoufia Governorate

ObjectiveTo identify the prevalence of β-thalassemia carriers among secondary school children for the prevention program of β-thalassemia and to update carrier rate data in Menoufia Governorate.Backgroundβ-thalassemia is the most prevalent hereditary disorder and is particularly prevalent among the Mediterranean people, and this geographical association is responsible for its naming.Patients and methodsThis study was conducted on 303 high school students aged 15–18 years from Shebin El-Kom, Menoufia Governorate, Egypt (62% women and 38% men). They were subjected to full history taking and clinical examination. Laboratory investigation included complete blood count, and serum ferritin level. High-performance liquid chromatography was done for samples with normal or high serum ferritin level.ResultsThe overall prevalence of anemia among the studied students was 38%. Microcytic type was the most common and represented 57% of anemic students. Men have higher mean hemoglobin values than women in different age groups. Three (1%) students of the total studied students were diagnosed to have the β-thalassemia trait. Moreover, there was a significant difference in ferritin level between β-thalassemia carriers and students diagnosed with iron-deficiency anemia. The mean value of hemoglobin A2 in students with β-thalassemia trait was 5.56 ± 0.42%.ConclusionThe prevalence of β-thalassemia carriers in high schools was about 1%. A full blood count with microcytosis, together with normal or high serum ferritin level, and hemoglobin A2 more than 3.5% were considered enough for the identification of β-thalassemia carriers in a screening process.

β-Hemoglobinopathies in the Lao People's Democratic Republic: Molecular diagnostics and implication for a prevention and control program.

A high frequency of β-thalassemia in Lao People's Democratic Republic necessitates the importance of complete molecular data before a prevention and control program could be established. Limited data are available for Lao PDR. We have now reported an extended information on the molecular basis of β-hemoglobinopathies in this population. The study was done on 519 unrelated Laos subjects requested for thalassemia investigation. Hematological data were recorded. Hb profiles were obtained using a capillary electrophoresis system. α-And β-globin genotyping was performed using PCR and related techniques. Among the 519 subjects, 287 (55.3%) were found to carry β-hemoglobinopathies based on Hb and DNA analyses. These included Hb E carriers (n=135), homozygous Hb E (n=47), β-thalassemia carriers (n=70), Hb E-β-thalassemia (n=25), homozygous β-thalassemia (n=4), heterozygous δβ0 -thalassemia (n=2), and carriers of the β-Hb variant (n=3). Mutation analysis identified in addition to the Hb E, 8 different β-thalassemia mutations including codon 17 (A-T), codons 41/42 (-TTCT), NT-28 (A-G), codons 71/72 (+A), IVS1-1 (G-T), 3.4kb deletion, an initiation codon (T-G) and IVS2-654 (C-T). Two δβ0 -thalassemia carriers (12.6kb deletion) and three subjects with Hb Hope (β136GGT-GAT ) were identified. Hematological features associated with these β-hemoglobinopathies were presented. β-hemoglobinopathies in the Laos population is heterogeneous. This information is relevant for setting up a molecular diagnostics and can provide a basis for genetic counseling and enable prenatal diagnosis.

Celocentesis for early prenatal diagnosis of hemoglobinopathy

Celocentesis is an invasive technique that can provide prenatal diagnosis of single-gene disorders, from as early as 7 weeks' gestation. The objective of this study was to examine the safety of celocentesis. In this prospective study, celocentesis was performed for prenatal diagnosis of hemoglobinopathy in 402 singleton pregnancies in which both parents were carriers of β-thalassemia or sickle cell disease trait. We assessed procedure-related maternal discomfort or pain, success of sampling and obtaining results, pregnancy outcome and postnatal follow-up. First, celocentesis was carried out at a median gestational age of 8.6 (range, 6.9-9.9) weeks and celomic fluid was successfully aspirated in 99.8% of cases. Second, 67% of women had no or only mild discomfort, 18% had moderate discomfort, 12% had mild-to-moderate pain and 3% had severe pain. Third, prenatal diagnosis from analysis of the celomic fluid was successful in 93.8% cases, and in the last 121 cases, it was always successful. Fourth, in all cases of successful sampling and analysis of celomic fluid, the diagnosis was concordant with results obtained from additional prenatal or postnatal testing. Fifth, in addition to diagnosis of hemoglobinopathy, quantitative fluorescence polymerase chain reaction analysis, which was performed to evaluate maternal contamination using several markers for chromosomes X, Y, 21, 18 and 13, led to the accurate diagnosis of chromosomal aneuploidy. Sixth, in all cases of an affected fetus diagnosed by celocentesis in which the parents chose termination of pregnancy, this was carried out < 10 weeks' gestation. Seventh, in 97.1% (298/307) of the continuing pregnancies there was live birth, in seven (2.3%) there was miscarriage and in two (0.7%) there was loss to follow-up. Eighth, fetal abnormalities were diagnosed in three (1%) cases, including unilateral transverse amputation of the forearm, unilateral moderate hydronephrosis and small-bowel duplication. All neonates were examined by a pediatrician and were found to be phenotypically normal, except for the three cases with a prenatally diagnosed defect. Celocentesis can be used for early prenatal diagnosis of genetic abnormalities, and the procedure-related risk of pregnancy complications appears to be low. Copyright © 2020 ISUOG. Published by John Wiley & Sons Ltd.

Relationship between platelet counts, mean platelet volume, platecrit and Beta Thalassemia Carriers

Aim: β-thalassemia carriers (BTC) is generally asymptomatic;however, in clinical practice, there is hypochromic microcytic mildanemia caused by a hereditary reduction in beta globin synthesis.In the literature, there is also some information about plateletindices in BTC. The aim of this study was to evaluate platelet indicesin children with BTC. In addition, we compared platelet indicesbetween anemia (Hb&amp;lt;11 g/dl) and non-anemia BTC (Hb ≥11 g/dl).Material and Method: A cross sectional study included a totalof 153 subjects aged 1-16 years were recruited from GaziantepUniversity Hospital outpatient clinics electronic database.Results: Platelet counts were normal in 90 patients with BTC.Thrombocytosis and thrombocytopenia were detected in 59(38.5%) and four (2.6%) patients, respectively. This study groupwas divided into two groups as group 1, cases&amp;lt;11 g/dl (n=86), andgroup 2, cases≥11g/dl (n=67) according to the hemoglobin levels.The children with the group 1 had significantly higher mean levelsof platelet counts and platecrit than those with group 2 (p&amp;lt;0.05).In the logistic regression test, linear correlation between plateletcounts and platecrit (r=0.94, p&amp;lt;0.01) was observed, whereas therewere inverse correlations between platelet counts and age (r=-0.32, p&amp;lt;0.01), mean platelet volume (r=-0.18, p&amp;lt;0.05), hemoglobin(r =-0.18, p&amp;lt;0.05).Conclusion: We found that both thrombocytosis andthrombocytopenia may occur in BTC. Herein we also foundsignificantly elevated platelet counts in BTC with anemia.

Molecular Characterization of β- and α-Globin Gene Mutations in Individuals with Borderline Hb A2 Levels

Elevated Hb A2 level (≥4.0%) is considered to be reliable parameter to identify β-thalassemia (β-thal) carriers. However, some β-thal carriers have been misdiagnosed as their Hb A2 levels are below 4.0%. In addition, coinheritance of α-thalassemia (α-thal) and β-thal might affect Hb A2 levels. Therefore, the aim of this study was to investigate the mutations of β- and α-globin genes in individuals with borderline Hb A2 levels in Thailand. Three hundred samples from individuals with Hb A2 levels of 3.5–3.9% were collected for molecular diagnosis of β-globin gene mutations. In addition, the α0-thal, α+-thal, Hb Constant Spring (Hb CS, HBA2: c.427T>C), and Hb Paksé (HBA2: c.429A>T) diagnostics were also performed. Sixteen samples (5.33%) had β-globin gene mutations, and codon 41/42 (–TTCT) (HBB: c.126_129delCTTT) was the most prevalent mutation. Ninety-eight samples (32.67%) had α-globin gene mutations including four Hb H (β4)-Hb CS disease, two Hb H disease, 13 heterozygous α0-thal, 11 homozygous α+-thal, two α+-thal/Hb CS, one α+-thal/Hb Paksé, 61 heterozygous α+-thal, and four Hb CS. Furthermore, seven cases of β-thal carriers coinheriting α-thal were observed, and five of them carried Hb H disease. High prevalence of both α- and β-thal in subjects with borderline Hb A2 levels suggested that molecular diagnosis of α- and β-thal should be performed, especially in a high prevalence area of thalasssemia carriers, for accurate diagnosis and genetic counseling to prevent and control new severe thalassemia cases. Moreover, β-thal carriers who coinherited Hb H disease might have reduced Hb A2 levels, leading to a misdiagnosis of β-thal in analysis programs.

Thalassemia and erythroid transcription factor KLF1 mutations associated with borderline hemoglobin A2 in the Thai population.

IntroductionElevated hemoglobin (Hb) A2 is an important diagnostic marker for β-thalassemia carriers. However, diagnosis of cases with borderline Hb A2 may be problematic. We described the molecular characteristics found in a large cohort of Thai subjects with borderline Hb A2.Material and methodsExamination was done on 21,657 Thai subjects investigated for thalassemia at Khon Kaen University, Thailand. A total of 202 subjects with borderline Hb A2 (3.5–4.0%) were selectively recruited and hematological parameters were recorded. DNA variants in α-, β-, δ-globin, and Krüppel-like factor 1 (KLF1) genes were examined using PCR.ResultsAmong 202 subjects, DNA analysis identified carriers of α+-thalassemia (n = 48; 23.8%), β-thalassemia (n = 22; 10.9%) and KLF1 mutations (n = 48; 23.8%). No molecular defect was observed in the remaining 84 (41.5%) subjects. Interaction of KLF1 and α-thalassemia was observed in 10 cases. Of the 22 β-thalassemia carriers, five β+-thalassemia mutations were identified with lower MCV and higher Hb A2. Seven KLF1 mutations were detected in 10 genotypes in subjects with higher MCV and Hb F. No β0-thalassemia, α-globin gene triplication or δ-globin gene mutation was detected.ConclusionsA large proportion of subjects with borderline Hb A2 are not β-thalassemia carriers and for those with β-thalassemia, only mild β+-thalassemia mutations were detected. Evaluation of the patients using Hb A2, Hb F and MCV values will help in selecting cases for further molecular analysis. The results should explain the unusual phenotype of the cases and facilitate a thalassemia screening program in the region.

Prevalence of β-haemoglobinopathies in Eastern India and development of a novel formula for carrier detection

Beta thalassemia is the commonest inherited monogenic disorder and India forms a major part of the thalassemia belt in the world. Effective screening programmes and proper prenatal diagnosis are the only ways to eradicate the disease. Haemoglobin high-pressure liquid chromatography (HPLC) is the screening method employed for detection of thalassemia carriers. The aim of this paper was to investigate the prevalence and demographic profiles of thalassemia carriers in Eastern India. Haemogram data was used to develop a novel haematological index for thalassemia carrier detection. This was a retrospective analysis of data collected from 21,695 individuals at thalassemia screening camps. The prevalence of the common hemoglobinopathies and their regional variations were noted. Using stepwise discriminant analysis, RBC indices were analysed to develop a novel formula to help distinguish β-thalassemia carriers from normal individuals. Out of the total population analysed, β-hemoglobinopathy carrier prevalence was around 10%. HbE was the commonest hemoglobinopathy in the region. There was no difference in the prevalence rates of thalassemia carriers amongst religious communities. The formula generated was expressed as outcome = RBCx6.59 + MCHx0.527 − (HCTx0.782 + MCHCx0.395 + RDWx0.02 + 1.365). Any integer value more than 0.5 indicated the probability of carrier status while a value less than 0.5 was normal. The formula had a negative predictive value of > 96% and an accuracy of 89%. This study provides an audit of the common β-hemoglobinopathies in Eastern India. The regional variations and prevalence of hemoglobinopathies highlighted here may guide public health efforts. The formula generated from RBC indices can be used to screen individuals prior to HPLC testing, thereby reducing overall costs of thalassemia screening in the country.

Detection of HBB:c.92+5G>C and HBB:c.108delC mutations in β-thalassemia carriers using high-resolution melting analysis.

The HBB:c.92+5G>C [known as IVSI-5 (GC)] and HBB:c.108delC [known as Cd 35 (del C)] are the β-globin gene mutations that commonly found in Indonesia. Detection of the mutation in the β-thalassemia carriers can be useful to prevent an increase in the number of β-thalassemia patients. High-Resolution Melting Analysis (HRMA) is the method that can detect the mutation rapidly. The aim of this study was to detect HBB:c.92+5G>C and HBB:c.108delC mutations of the β-thalassemia carriers using HRMA. DNA was isolated from blood archive of ten hematologically proved β-thalassemia carriers. Detection of mutations was carried out by HRMA and then confirmed by sequencing. HRMA was performed by using two pairs of specific primers. One pair of primer targeted the region of HBB:c.92+5G>C and the other targeted the region of HBB:c.108delC. The results of detection of mutation using HRMA then were confirmed by sequencing. A specific primer pair covering the region of HBB:c.92+5G>C to HBB:c.108delC were used for sequencing. The results of HRMA showed that the HBB:c.92+5G>C and HBB:c.108delC mutations found in 50% and 30% samples, respectively. The HRMA results can be confirmed by sequencing in all samples. It can be concluded that HRMA can be used to detect HBB:c.92+5G>C heterozygote and HBB:c.108delC heterozygote mutations.

Haplotype Analysis in Carriers of β-globin Gene Mutation Facilitates Genetic Counseling in β-thalassemia: A Cross-Sectional Study in Kerman Province, Iran

β-thalassemia is characterized by reduced synthesis of the hemoglobin beta chain that results in microcytic hypochromic anemia and reduced amounts of hemoglobin A (HbA) on hemoglobin analysis. β-thalassemias are caused by mutations in the β-globin gene, inherited in an autosomal recessive manner. Determining molecular defects in couples carrying β-thalassemia is a prerequisite for prenatal diagnosis of the disease. In this regards, database of β-globin gene haplotypes facilitates mutation detection of the gene and helps genetic counselors to reach the goals of β-thalassemia prevention program. In this cross-sectional study, 255 couples attended genetic counseling between December 2017 and January 2019 in Afzalipour Hospital, Kerman University of Medical Scinces, Kerman, Iran as suspicious of β-thalassemia carriers. Furthermore, they were investigated using amplification refractory mutations system-polymerase chain reaction and restriction fragment length polymorphism methods for mutation screening and haplotype analysis of polymorphic sites in β-globin gene cluster, respectively. We identified 20 different types of β-globin gene mutation in 449 β-thalassemia carriers. Analysis of the pattern of Hind III/Gγ, Hinf I/5'β, Hinc II/3'Ψβ, Rsa I/5'β, AvaII/β and Hind III/Aγ polymorphic sites in 257 alleles of informative families revealed 17 different haplotypes. Haplotype 1 (77.24%) showed strong linkage with the most common mutation IVSI-5 while haplotype 5 (66.67%) was associated with the second frequent mutation IVSII-1. To our knowledge, these β-globin haplotypes are reported for the first time which are different with those found in other parts of Iran. The current haplotypes pattern data makes the counseling of β-thalassemia carriers more straightforward and the process of mutation screening faster and more accurate.

Long-Molecule Sequencing: A New Approach for Identification of Clinically Significant DNA Variants in α-Thalassemia and β-Thalassemia Carriers

Multiple molecular tests are currently needed for accurate carrier testing for thalassemia. Therefore, long-molecule sequencing (LMS) was evaluated as an alternate on the PacBio Sequel platform for genotyping carriers of α-thalassemia or β-thalassemia. Multiplex long PCR was used to generate representative amplicons for the α (HBA1/2) and β (HBB) gene loci. Following LMS, circular consensus sequencing reads were aligned to the hg19 reference genome and variants called using FreeBayes software version 1.2.0. In a blinded study of 64 known carrier samples, all HBA1/2 and HBB variants detected by LMS were concordant with those independently assigned by targeted PCR assays. For HBA1/2 carrier samples, LMS accurately detected the common South East Asian, -α3.7, and -α4.2 deletions and four different rare single-nucleotide variants (SNVs). For HBB carrier samples, LMS accurately detected the most common Chinese insertion and deletion variant c.126_129delCTTT and 14 different SNVs/insertions and deletions and could discriminate compound heterozygous SNVs (trans configuration) and identify variants linked to benign SNPs (cis configuration). Overall, LMS displayed the hallmarks of a scalable, accurate, and cost-effective genotyping method. With further test coverage to additionally include detection of other clinically significant HBA1/2 copy number variations, such as the Thai, Mediterranean, and Filipino deletions, LMS may eventually serve as a comprehensive method for large-scale thalassemia carrier screening.

Pengetahuan Tentang Talasemia pada Mahasiswa Kedokteran dan Dokter Umum di Bandung serta Prevalensi Karir β-Thalassemia

Latar Belakang: Talassemia mayor menempati urutan ke-5 beban BPJS. Pengetahuan tenaga kesehatan yang baik tentang talasemia mendorong masyarakat melakukan deteksi dini karir talasemia. Tujuan penelitian ini adalah mengeksplorasi pengetahuan tentang talasemia pada mahasiswa kedokteran dan dokter umum di Bandung, serta mengetahui prevalensi karir β-talasemia. Metode: Desain penelitian analitik menggunakan kuesioner untuk membandingkan pengetahuan. Prevalensi anemia defisiensi besi dan karir β-thalassemia dideskripsikan dengan indeks Mentzer (MCV/RBC) dan Shine&amp;Lal (MCV*MCV*MCH/100). Hasil: Pengetahuan mahasiswa kedokteran (n597) dan dokter umum (n171) cukup baik. Walaupun demikian, terdapat perbedaan signifikan; dokter umum usia &gt;30 tahun memiliki pengetahuan lebih rendah dari mahasiswa. Pemeriksaan darah dihadiri mahasiswa dengan pengetahuan yang lebih baik (p 0,036). Tipe anemia pada mahasiswa (7,9%) memiliki distribusi berbeda menurut indeks Mentzer vs. Shine&amp;Lal, yaitu defisiensi besi (5,3% vs. 3,2%) dan karir β-talasemia (2,6% vs. 4,7%). Kesimpulan: Pengetahuan tenaga kesehatan tentang talasemia perlu ditingkatkan, mengingat 6-10% penduduk Indonesia adalah karir talasemia. Diperlukan pemeriksaan lanjutan untuk skrining karir talasemia.

Advances in genome editing: the technology of choice for precise and efficient β-thalassemia treatment.

Beta (β)-thalassemia is one of the most significant hemoglobinopathy worldwide. The high prevalence of the β-thalassemia carriers aggravates the disease burden for patients and national economies in the developing world. The survival of β-thalassemia patients solely relies on repeated transfusions, which eventually results into multi-organ damage. The fetal γ-globin genes are ordinarily silenced at birth and replaced by the adult β-globin genes. However, mutations that cause lifelong persistence of fetal γ-globin, ameliorate the debilitating effects of β-globin mutations. Therefore, therapeutically reactivating the fetal γ-globin gene is a prime focus of researchers. CRISPR/Cas9 is the most common approach to correct disease causative mutations or to enhance or disrupt the expression of proteins to mitigate the effects of the disease. CRISPR/cas9 and prime gene editing to correct mutations in hematopoietic stem cells of β-thalassemia patients has been considered a novel therapeutic approach for effective hemoglobin production. However, genome-editing technologies, along with all advantages, have shown some disadvantages due to either random insertions or deletions at the target site of edition or non-specific targeting in genome. Therefore, the focus of this review is to compare pros and cons of these editing technologies and to elaborate the retrospective scope of gene therapy for β-thalassemia patients.

Molecular analysis of α-thalassemia and β-thalassemia in Quanzhou region Southeast China

AimsThalassemia is one of the most prevalent inherited disorders in south China. However, there still has no comprehensive research on molecular characterisation of α-thalassemia and β-thalassemia in the Quanzhou region...

Genetic epidemiology of beta-thalassemia in the Maldives: 23years of a beta-thalassemia screening program.

The Maldives is an archipelago of 407,660 people according to population census of 2014, made up of 20 atolls, which has one of the highest prevalence of β-thalassemia worldwide. However, there is a dearth of studies related to β-thalassemia in the Maldives; therefore, in this study, we aimed to investigate the genetic epidemiology of β-thalassemia in Maldives. Blood samples were collected from 110,504 participants (1992-2015). Hemoglobin and RBC indices were measured on automated hematology analyzers. The quantitation of hemoglobin, HbA2, Hb F, and other abnormal Hb variants were assessed by HPLC. Molecular analysis was performed for the most common mutations in Southeast Asia for only 874 individuals either heterozygous or homozygous for these mutations using reverse dot blot hybridization. We screened 110,504 individuals for β-thalassemia between 1992 and 2015, which is~30% of the entire population. The β-thalassemia carrier frequency was estimated to be 16.2%. Molecular diagnosis of 874 β-thalassemia carriers/major was performed for the most common seven mutations in Southeast Asia; of these, 139 patients were diagnosed as β-thalassemia major. This analysis showed that the most common mutations were IVS1+5G>C, (678; 77.6%), followed by the CD 30 (136; 15.6%). The least frequent mutation was FS8/9, (1, 0.001%), followed by IVS1+1G>T and CD15 (2; 0.2%). The frequency of β-thalassemia varies significantly among the 20 different atolls in Maldives. This study is expected to improve genetic counseling, creating awareness, enhance premarital screening, and customize the prevention and treatment strategies based on the needs of each atoll.

Multi-Locus Models to Address Hb F Variability in Portuguese β-Thalassemia Carriers

Hb F production is under the influence of major quantitative trait loci (QTL). The present study aims: i) to replicate the association with Hb F for representative genetic variants in the three major Hb F QTLs in a Portuguese sample of β-thalassemia (β-thal) carriers; and ii) to test different genetic multi-locus models to account for the genetic component of Hb F variation. A population sample of 79 Portuguese β-thal carriers (39 males, 40 females), aged between 2 to 70 years old, were genotyped for polymorphisms in the locus control region (LCR)-5’ hypersensitive site 4 (5’HS4) rs16912979, XmnI-HBG2 rs7482144, BCL11A rs1427407 and HMIP rs66650371, using standard biomolecular procedures. Univariate linear regression models were used to test for genetic associations with Hb F. The minor alleles of the individual variants BCL11A rs1427407 (T) (0.165), HMIP rs66650371 (3 bp del) (0.247) and XmnI-HBG2 rs7482144 (T) (0.196), were found to be significantly associated with increased levels of Hb F (p = 0.029, p = 0.002 and p = 0.0004, respectively), explaining about 6.0, 12.0 and 15.0% of Hb F variation, respectively. In a multiple linear regression approach, the three loci accounted for about 30.0% of Hb F variance. Two genetic risk scores (GRS), rationalizing the number of minor alleles into a single genetic variable, explained about 30.0 and 32.0% of the Hb F variation. In conclusion, we replicated in β-thal carriers previously reported associations with Hb F. Multi-locus models combining three representative variants of Hb F influencing QTLs can explain a larger amount of Hb F variability.

Mean corpuscular volume/mean corpuscular hemoglobin values are not reliable predictors of the β-thalassemia carrier status among healthy diverse populations of Himachal Pradesh, India.

BACKGROUND:Himachal Pradesh is a hill state in North India in the Western Himalayas. β-thalassemia is a genetic disorder of hemoglobin inherited in an autosomal recessive manner that results in defective globin production leading to the early destruction of red blood cells. β-thalassemia has long been neglected in Himachal Pradesh due to popular belief that it runs along “Lahore-Gujarat-Punjab” belt in India. Therefore, there is no β-thalassemia testing facility currently in the state.METHODS:To estimate the prevalence of β-thalassemia carriers, we calculated the sample size based on probability proportional to size self-weighing design. In each of 20 selected colleges, 111 students having an age of 18–25 were tested for high-performance liquid chromatography (HPLC) and complete blood count. Some were further tested for the mutations. We computed sensitivity, specificity, positive predictive value (PPV) and negative predictive value, and receiver operating characteristic curve for mean corpuscular volume (MCV) and mean corpuscular hemoglobin (MCH) red cell parameters.RESULTS:Of the 2220 students, 57 were found to be β-thalassemia carrier by HPLC. The overall prevalence rate was 2.6% which translates to probable 180,000 β-thalassemia carriers in Himachal Pradesh. Six districts bordering highly endemic Punjab had a higher prevalence. Hemoglobin D-Punjab, Heterozygous-Iran Trait, and raised fetal hemoglobin were found. Thalassemia major and sickle cell disease were not found. Anemic status or MCV/MCH parameters were not found to be reliable predictors of thalassemia carrier status among the healthy populations of HP. The predominant mutation found was IVS 1–5 G > C.CONCLUSION:Popular ongoing strategy for screening with MCV and MCH has low-PPV and can miss upto 37% of true thalassemia carriers. HPLC is better strategy for screening carriers and reduces further spread of thalassemia.

Double heterozygous for hemoglobin E and Beta thalassemia: A case study

Haemoglobinopathies and thalassemias are inherited conditions, being diagnosed with increasing prevalence in India. An accurate diagnosis of β-thalassemia carriers, homozygous patients, double heterozygous patients and identification of different structural hemoglobin variants is important for epidemiological studies as well as for management and prevention of the major hemoglobin disorders. The phenotypic variability of Hb E/β-thalassaemia and the paucity of long-term clinical data, present challenges in providing definitive diagnosis and management of such patients. This case was clinically labelled as Thalassaemia intermedia and was confirmed as Double heterozygous for HbE and Thalassaemia. Family study was also done.

Association of Consanguinity and ABO Blood Groups with β-thalassemia major in District Dadu and Hyderabad, Pakistan

Consanguineous marriages are the deeply rooted social trend in Pakistan, which lead to the high prevalence of inherited diseases. Thalassemia is an inherited disorder characterized by the abnormal synthesis of hemoglobin leading to anemia. β-thalassemia is the most common inherited disorder in Pakistan particularly in Sindh. The patients of β-thalassemia need repeated transfusion, which might cause complications causing the high rate of mortality in blood transfusion dependent β-thalassemia patients. Several studies have previously reported the high prevalence of β-thalassemia in Pakistan, however, the prevalence of β-thalassemia in the siblings borne from β-thalassemia carrier parents and association of ABO blood group with β-thalassemia have not been extensively studied. The purpose of this study was to find out the prevalence of β-thalassemia in the siblings of β-thalassemia carriers parents. This study was also set to find out the association of β-thalassemia with ABO blood groups. This was a cross sectional study carried out from August 2016 to July 2017 in the Thalassemia centers of district Dadu and district Hyderabad. In this study, 168 children from 50 families were selected for the study. The results indicate that almost half of the births 44.64% from β-thalassemia carriers are the β-thalassemia patients. B blood group was found to be higher in both in male and female β-thalassemia patients. Male had higher prevalence of β-thalassemia than female children. The pattern of ABO blood group distribution was B > O > A > AB, and for the RH factor it was RH + ve > Rh –ve. Conclusively, this study indicates the higher prevalence of β-thalassemia in siblings borne from β-thalassemia carrier’s parents. β-thalassemia was higher in male children and B blood group was higher than other blood groups.

Analysis on the Genotype of 5018 Cases of Thalassemia in Hunan Area

To investigate the type and distritution of thalassemia gene mutaitons in Hunan area, so as to provide evidence for prenatal screening, diagnosis and reduction of birth defects. A total of 5018 cases from Maternal and Children Health Hospital of Hunan from June 2017 to Dec 2018 were undergone thalassemia gene mutation analysis. The reverse dot blot hydridization was used to detect 6 kinds of genotypes of α-thalassemia and 17 kinds of point mutations of β-thalassemia, and the detected data were analyzed statistically. 889 cases (55.9%) of α-thalassemia carriers were found, including 385 cases of silent α-thalassemia, 488 cases of α-thalassemia trait, 16 cases of Hb H disease. --SEA/αα was the most common genotype in α thalassemia. 664 cases (41.7%) were diagnosed as β-thalassemia carriers, heterozygotes accounted for 99.8% (663/664), IVS-Ⅱ-654, CD41-42M and CD17M were the main genotypes, and compound heterozygote accounted for 0.2% (1/664). 38 cases were diagnosed as α-thalassemia combined β-thalassemia. The constituent ratio of thalassemia gene mutations in Hunan has regional characteristics, --SEA/αα is the most common genotype in α-thalassemia carrier. IVS-Ⅱ-654, CD41-42 and CD17 are common ones in β-thalassemia. The frequency of α-thalassemia combined with β-thalassemia is high.

Analysis on the Genotype of 5018 Cases of Thalassemia in Hunan Area

To investigate the type and distritution of thalassemia gene mutaitons in Hunan area, so as to provide evidence for prenatal screening, diagnosis and reduction of birth defects. A total of 5018 cases from Maternal and Children Health Hospital of Hunan from June 2017 to Dec 2018 were undergone thalassemia gene mutation analysis. The reverse dot blot hydridization was used to detect 6 kinds of genotypes of α-thalassemia and 17 kinds of point mutations of β-thalassemia, and the detected data were analyzed statistically. 889 cases (55.9%) of α-thalassemia carriers were found, including 385 cases of silent α-thalassemia, 488 cases of α-thalassemia trait, 16 cases of Hb H disease. --SEA/αα was the most common genotype in α thalassemia. 664 cases (41.7%) were diagnosed as β-thalassemia carriers, heterozygotes accounted for 99.8% (663/664), IVS-Ⅱ-654, CD41-42M and CD17M were the main genotypes, and compound heterozygote accounted for 0.2% (1/664). 38 cases were diagnosed as α-thalassemia combined β-thalassemia. The constituent ratio of thalassemia gene mutations in Hunan has regional characteristics, --SEA/αα is the most common genotype in α-thalassemia carrier. IVS-Ⅱ-654, CD41-42 and CD17 are common ones in β-thalassemia. The frequency of α-thalassemia combined with β-thalassemia is high.