Higher Hb A2 Levels Research Articles

Hemoglobin Variants in Patients Attending Aden Diagnostic Center by High Performance Liquid Chromatography

Introduction: High performance liquid chromatography (HPLC) is emerging as the method of choice for initial screening and diagnosis of hemoglobinopathies. The use of alkaline and acid gel electrophoresis may result in incorrect diagnosis of hemoglobinopathies. The aim of the study is to investigate the hemoglobin pattern using the HPLC and to correlate the hematological profile with the types of hemoglobin. Methods: A cross-sectional study was conducted in Aden Diagnostic Center from July– December 2022. Over a six-month period, 250 samples of patients aged between six months to thirty years, were evaluated by HPLC for detection of hemoglobinopathies using the Lifotronic Hemoglobin Analyzer H9: β-thalassemia Analysis Mode. Red blood cell and red cell indices were determined using automated hematology analyzer. Results: A total of 152 samples (60.8%) showed different abnormal hemoglobin variants. Sixty-four (25.6%) were diagnosed to have sickle cell anemia, 46 (18.4%) as sickle cell trait, two (0.8) as beta – heterozygous thalassemia based on high level of HbA2 (>3.9%), four (1.6%) as beta – homozygous thalassemia (HbF 25–91%), 18 (7.2%) as compound heterozygous state of sickle - β+ thalassemia, 17 (6.8%) as beta thalassemia trait, and one (0.4%) sample had HbD variant on HPLC was diagnosed as HbD trait. Conclusion: H9-HPLC is suitable for the routine investigation of hemoglobinopatheis because it is very powerful tool in the evaluation of Hb variants, rapid assay time and accurate quantification.

Elevated foetal haemoglobin in tribal sickle cell anaemic patients: Blessing in disgust?

Sickle cell anaemia is a molecular disease. WHO recognises it as a global public health problem. In India, it is common among tribal communities. Increased HbS is a culprit. Therapeutic research is focused on maintaining high levels of HbF and decreasing 2,3, BPG to target disease. To assess the role of naturally compensated haemoglobin variants in tribal Sickle cell anaemic patients of North East Gujarat. Prospective, analytical, case control study conducted on randomly selected fifty tribal Sickle cell anaemic patients having disease for more than 5 years. Fifty age and sex matched, healthy control subjects. Each fifty Tribal sickle cell anaemic patients and healthy control were included in the study. Total Haemoglobin level, Sickling test by NESTROFT method and Haemoglobin variants were analysed by alkaline haemoglobin electrophoresis. Frequencies of clinical crises were recorded by oral questioning. The results were analysed using SPSS version 20. Student unpaired t- test was employed to assess the significance of the differences. P-values < 0.05 considered statistically significant. We observed decreased levels of total haemoglobin, high levels of HbF and HbA2 along with reduced HbA0. Compensatory increase of HbF in tribal SCA patients have shown lower frequency of clinical crises. Reduced HbA0 in sickle cell anaemia is compensated by naturally elevated HbF and HbA2 in tribal patients which has a beneficial influence on their general health.

Common mutation analysis of beta-thalassemia carriers by amplification refractory mutation system-polymerase chain reaction in cases diagnosed by capillary zone electrophoresis at National Public Health Laboratory, Nepal

Abstract BACKGROUND: Beta (β)-thalassemia is a globally prevalent genetic disorder with over 350 known mutations in the β-globin gene. Intervening-sequence (IVS) 1–5 (G→C), 619 bp deletion, IVS 1–1 (G →T), C-15 (G→A), frameshift (FS) 41/42 (−CTTT), FS 8/9 (+G), codon 19, A-G, and codon 17 (A→T) are some common mutations in β-thalassemia. This study aimed to identify and analyze the common mutation by amplification refractory mutation system polymerase chain reaction in β-thalassemia carriers diagnosed by capillary zone electrophoresis (CZE) at National Public Health Laboratory. MATERIALS AND METHODS: On the basis of archived data, the CZE performed on 781 samples between June 2019 and July 2022 was analyzed. Without regard to age, gender, race, or address, 121 samples were ultimately selected for mutation analysis during this time because they were identified as positive for the β-thalassemia traits based on high HbA2 levels of more than 3.5%. RESULTS: IVS 1–5 (G→C) was the most common mutation followed by 619 bp deletion. Five mutations namely IVS 1–5 (G→C), 619 bp deletion, FS 41/42 (−TTCT), FS 8/9 (+G), and codon 15 (G→A) accounted for 84.3% of cases. A single mutation was seen in 87 cases (71.9%), more than one mutation in 15 cases (12.4%) whereas 19 cases (15.7%) did not show any of the mutations tested. CONCLUSION: IVS 1–5 (G-C) is the most prevalent mutation in Southeast Asian nations, with the 619 bp deletion predominant in the Tharu community. Further research is needed to understand diverse ethnic groups and regions, enabling prenatal diagnostics and genetic counseling for β-thalassemia prevention.

A First Clinical and Molecular Study of Rare IVS-II-806 (G > C) (HBB:c.316-45G > C) Variant in the β-globin Gene: A Possibly Benign Variant.

β-thalassemia is a common genetic disease affecting a single gene, disease with a high incidence in South China. We hereby, aim to provide the clinical and hematological features of a rare β-globin gene variant in the Chinese population. Ten subjects from three unrelated Chinese families were enrolled in this study. Hematological analysis and thalassemia gene testing were preformed to screen for common α and β-thalassemia variants. Gap-polymerase chain reaction (Gap-PCR) and DNA sequencing were utilized to examine the rare or novel thalassemia variants. Six cases were identified carrying the rare IVS-II-806 (G > C) (HBB:c.316-45G > C) variant in the β-globin gene. The proband in family 1 carry three rare β-globin gene mutations including CD39 (C > T), IVS-II-81 (C > T) and IVS-II-806 (G > C) combined with a --SEA/αα deletion, exhibiting the β-thalassemia trait. Further pedigree investigation indicated that the genotype of the proband in family 1 was --SEA/αα, βCD39 (C>T), IVS-II-81(C>T)/βIVS-II-806(G>C). Meanwhile, the twin girls in family 1 carrying the IVS-II-806 (G > C) mutation demonstrated a normal hematological phenotype. In family 2, the proband and his sister carry the IVS-II-806 (G > C) mutation, eliciting high levels of Hb A2 and slightly low levels of MCV and MCH. Moreover, the proband in family 3 carrying the same mutation exhibited a slightly low MCV level as well. In this study, clinical and hematological analysis of the IVS-II-806 (G > C) mutation was first conducted within the Chinese population, with results indicating that it may be a benign variant.

HbA2 induction: the merit of pancellularity in sickle cell disease.

HbA2 induction: the merit of pancellularity in sickle cell disease.

A Chinese Male with Normal Hematological Indices and High Hb A2 Levels in β-Thalassemia Trait

β-Thalassemia (β-thal) is a common hematological disorder in the Guangxi Zhuang Autonomous Region of Southern China. Heterozygous β-thal is usually associated with reduced hematological indices and increased Hb A2 levels. However, the preventive program of the regional government only conducts the screening of hematological indices [complete blood count (CBC)] especially at primary hospitals. In this study, we describe a male β-thal patient presenting normal hematological indices but with a high Hb A2 level. We proposed that hemoglobin (Hb) analysis and CBC should be performed together in the preventive screening program in regions with a high thalassemia incidence to avoid misdiagnosis.

Characterization of Two Novel Deletions Involving the 5′ Region of the β-Globin Gene

We report two novel β-thalassemia (β-thal) deletions involving the 5′ region of the β-globin gene (HBB). The first deletion spans 538 bp and removes the β-globin promoter, 5′ untranslated region (5′UTR) and most of exon 1. This deletion was identified in a 3-year-old Vietnamese boy with non transfusion dependent Hb E (HBB: c.79G>A)/β0-thal. The second deletion spans 1517 bp and removes the β-globin gene promoter, 5′UTR, and exons 1 and 2. This deletion was identified in two unrelated adults of European descent who had β-thal trait with unusually high Hb A2 levels. Deletions such as these are generally associated with higher levels of Hb A2 and Hb F than typical β-thal alleles, which may ameliorate the severity of the disease.

A Family with γ-Thalassemia and High Hb A2 Levels

We describe a family carrying a γ-globin gene deletion associated with an increase of Hb A2 level beyond the normal range. The family included the proband, his sister and their father, all with increased Hb A2 and normal Hb F levels. The proband and his sister showed borderline values of mean corpuscular volume (MCV) and reduced values of mean corpuscular hemoglobin (Hb) (MCH). The proband was referred to our Medical Genetics Service for preconception counseling together with his partner, a typical β-thalassemia (β-thal) carrier. The results were negative for the most frequent α-thalassemia (α-thal) mutations, and had no significant sequence variations of the coding sequences and promoter of the β- and δ-globin genes. Quantitative analysis by multiplex ligation-dependent probe amplification (MPLA) of the β-globin gene cluster detected a heterozygous deletion, ranging between 2.1 and 4.7 kb, in the proband, his sister and the father. The deletion involved the Gγ gene and Gγ-Aγ intergenic region, whereas the 3' region of the Aγ gene was preserved. A subsequent gap-polymerase chain reaction (gap-PCR) showed that a hybrid GAγ fusion gene was present. The deletion segregated with the elevation of Hb A2. The MLPA analysis of the β-globin gene cluster in 150 control alleles excluded a common polymorphism. Despite stronger evidence being needed, the described family suggests a possible role of this γ-globin gene deletion in contributing to Hb A2 elevation, possibly by altering the transcription regulation of the cluster. We propose γ-globin gene dosage analysis to be performed in patients with unexplained elevated Hb A2 levels.

Large Deletions Involving the Beta Globin Gene Complex: Genotype-Phenotype Correlation of 119 Cases

Background: Large deletions involving the beta globin complex are relatively rare. They can be categorized generally into five groups by deletion size and/or location: 1) beta zero thalassemia (BZT); 2) delta beta thalassemia (DBT); 3) hereditary persistence of fetal hemoglobin (HPFH); 4) gamma delta beta thalassemia (GDBT); and 5) epsilon gamma delta beta thalassemia (EGDBT). These deletions are not well understood but often have significant clinical impact, either when present alone or in combination with other hemoglobin mutations. In this study, we analyze phenotypic and molecular data on a large number of cases with deletions in the beta globin gene complex to better classify these five groups of deletions as they occur in isolation.Methods: A query of the routine clinical testing patient files from the Mayo Clinic Metabolic Hematology and Molecular Genetics Laboratories from 2010 to 2015 identified 179 patients with a deletion confirmed by a Multiplex Ligation-dependent Probe Amplification (MLPA) assay. Twenty-four probes sets were placed from the 5' locus control region (LCR) to the 3' hypersensitivity region, spanning the beta globin gene complex. Using a Luminex LX200 flow cytometer, a gene dosage ratio was calculated for each probe set using the median fluorescent intensity value collected. The size and location of the deletion and patient phenotype were compared.Results: Of the 179 total cases, the following large deletions were identified: beta gene (HBB) (n = 47), delta (HBD) through HBB (n = 105), A-gamma (HBG2) through HBB (n = 20), and locus control region (LCR) through HBB (n = 7). One case had a deletion involving the LCR epsilon with the rest of the complex left intact. A subset (n = 60) of cases had compound hemoglobin mutations that altered the phenotype. The BZT cases had relatively high Hb A2 levels and variable Hb F levels consistent with promotor region loss. The main differences between DBT and HPFH included Hb F and Hb A2 levels. GDBT cases presented with median Hb F levels higher than that observed in DBTs, normal Hb A2, and microcytic anemia. EGDBT cases had variable features according to age of the patient and Hb F level; severe microcytic anemia was observed in neonates, milder microcytic anemia in young children, and microcytosis without anemia in an adult case. The phenotypic features of 119 patients with isolated large deletions are compiled in table 1.Conclusion: In general, all five categories of large deletions in an isolated heterozygous state can present with microcytic anemia and are typically benign with the exception of transient severe microcytic anemia in neonatal EGDBT cases. Although phenotypes associated with large deletions involving the beta globin gene complex are frequently distinctive, significant phenotypic overlap can be seen in a subset of cases. These cases require molecular analysis due to their clinical importance when in combination with another beta globin gene complex mutation for an adequate diagnosis and treatment approach.Table 1Deletion typeAgenHbF (%)HbA2 (%)Hb (g/dL)MCV (fL)RBC (10^12/L)RDW (%)MCH (pg/cell)BZT206.3 (0.6-94.4)6.8 (3.4-11.6)11.1 (8.3-14.5)65.4 (60.8-77.2)5.4 (4.2-6.2)19.2 (16.6-21.2)20.9 (18.3-25.7)DBT5610.6 (2.7-22.4)2.7 (2.5-3.1)11.7 (8.6-14.4)68.9 (61.3-83.5)5.3 (4.1-7.3)21.4 (18.2-26.8)21.6 (19.9-39.2)HPFH2325.9 (17.6-39.7)2.0 (1.5-2.4)11.6 (8.1-16.7)78.4 (60.2-101.9)4.4 (3.0-6.3)17.5 (14.1-22.3)25.4 (17.6-29.7)GDBT1413.3 (8.2-19.0)2.6 (1.8-2.7)11.0 (8.6-14.1)72.5 (57.9-82.1)5.1 (3.5-6.2)20.6 (17.4-23.5)22 (17.9-25.1)EGDBT*28 Y10.3313.359.46.915.419.21-4 Y30.9 (0-1.6)3.2 (2.9-3.5)9.5 (8.8-13.3)57.8 (57.6-59.4)5.2 (4.9-6.9)16.6 (15.4-17.4)18.5 (18.1-19.2)<6 month221.4 (14.8-27.9)2.6 (2.2-2.9)6.3 (6.0-6.6)61.3 (59.9-62.6)3.4 (3.3-3.3)21.5 (21.2-21.7)18.4 (18.1-18.7)medians, (min, max); *stratified by age DisclosuresNo relevant conflicts of interest to declare.

THE ROLE OF COMPLETE BLOOD COUNT IN THE DIAGNOSIS OF HEMOGLOBIN E IN PSEUDO HIGH LEVEL OF HEMOGLOBIN A2

Aim: To evaluate the usefulness of complete blood count (hemoglobin concentration, MCV: mean corpuscular volume, and MCH: mean corpuscular hemoglobin), in diagnostic of hemoglobin E (HbE) when hemoglobin analysis showed pseudo high level of HbA2. Methods: Secondary data were obtained from laboratory records of patients who were referred to the GenNeka Genetic Clinic, Eijkman Institute for Molecular Biology, Jakarta, for thalassemia screening. The patients employed were heterozygous HbE, compound heterozygous HbE with other β-thalassemia mutations, homozygous HbE, and co-inheritance with αthalassemia, that was confirmed by molecular analysis. Complete blood count (CBC) was examined using an automated blood cell analyzer. HbA2 level was measured by HPLC. Molecular analysis was performed by PCR-RFLP method. Hemoglobin concentration, MCV, and MCH values will be presented as a mean or median, and will be compared between heterozygous HbE and compound heterozygous HbE. A comparison was also done between males and females in the heterozygous HbE group. Homozygous HbE and co-inheritance with α-thalassemia will be described as an extrapolation. Results: The hemoglobin concentration, MCV, and MCH values were significantly different between heterozygous HbE and compound heterozygous HbE. Only the hemoglobin concentration and the MCV values were significantly different between males and females in the heterozygous HbE group. Conclusion: CBC is useful in assisting the differentiation of HbE types in misleadingly high HbA2 levels. The sex of the patient has to be considered in the interpretation of CBC results.

Mutation Screening of the Krüppel-Like Factor 1 Gene Using Single-Strand Conformational Polymorphism in a Cohort of Iranian β-Thalassemia Patients

The Krüppel-like factor 1 (KLF1) is an essential erythroid-specific transcription factor. Mutations in the human KLF1 gene have different phenotypic effects, ranging from increased Hb F levels to the disruption of erythropoiesis. Here, we screened 227 Iranian β-thalassemia (β-thal) patients for the presence of KLF1 mutations by using the single-strand conformational polymorphism (SSCP) approach. Our aim was to assess the potential effect of these mutations on the β-thal disease severity. After screening, two variants were found. One patient carried a potentially deleterious variant (Polyphen-2) in exon 2 (p.F182L). Another patient was homozygous for a previously unreported intronic variant (KLF1: c.911 + 84A > G). The patient with the p.F182L variant (KLF1: c.544T > C) had noticeably high Hb A2 levels (7.6%), consistent with the phenotypic effect of several previously characterized KLF1 mutations in the same exonic region. In addition, he had higher platelet counts (1,069,000/μL) compared to other patients in the cohort.

Use of HbA2 As a Discriminator for S/Beta Thalassaemia in a Nigerian Setting,

Abstract 4206An integral part of an EU-UNDP funded pilot sickle cell screening project, was the installation, in Abuja (Federal Capital Territory) Nigeria, June 2010, of a High Performance Liquid Chromatography (HPLC) instrument. Prior to the installation, haemoglobinopathy screening was carried out using only unstained paper electrophoresis. Minor bands were difficult to visualise and the proportions of haemoglobins were not measured. Full blood count (FBC) data was also not routinely available. Therefore awareness of both alpha and beta thalassaemia was low as was the implications of coinheritance of beta thalassaemia with haemoglobin (Hb) S.Stratified community surveys were carried out with samples collected as Guthrie card blood spots; children aged less than 6 months, and whole blood; children aged between 6 months and 5 years. Blood spot samples were analysed using newborn sickle cell screening reagents and whole blood samples using beta thalassaemia short reagents, the later allowing accurate Hb A2 and Hb F measurement. Samples were processed on a Biorad™ Classic (instrument and reagents, Biorad, Hercules, CA.). Reporting algorithms were defined for both reagent sets. Using the beta thalassaemia reagents, Hb S/beta thalassaemia was considered when Hb S was predominant, Hb A absent or significantly reduced and the Hb A2>5.Over 10,000 samples were analysed, 410 had sickle cell disease, of which 370 were transported to London for further analysis, 70 of these had an Hb A2>5%, mean and range 5.9(5.1 – 9.1)%. To validate the algorithm 31 samples (Hb A2 3.5 – 7.4%), were selected for beta gene sequencing (Mai et al, 2004) and/or PCR analysis for the 7 common alpha gene deletions (3.7kb, 4.2kb, SEA, MED, THAI, FILL, 20.5kb and triplicated alpha gene locus, anti 3.7kb), (Chong et al, 2000, Wang et al, 2003). Five samples had an Hb A2of 3.5 – 4.9%, 2 with Hb A present (23 and 25%), all were Hb SS, 4 negative for alpha thalassaemia deletions and 1 heterozygous for the alpha 3.7kb deletion. Sixteen samples had an Hb A2 of 5.0 – 5.9%, all were Hb SS, 5 negative for alpha thalassaemia deletions and 11 heterozygous for the alpha 3.7kb deletion. Seven samples had an Hb A2 of 6.0 – 6.9%, 6 were Hb SS, 1 negative for alpha thalassaemia deletions, 1 heterozygous and 4 homozygous for the alpha 3.7kb deletion. One, Hb A2 6.9%, was a compound heterozygote for Hb S/ beta zero codon 106/107(+G) mutation. Three samples had an Hb A2 of 7.0 – 7.4%, review of chromatograms indicated that all showed poor chromatography due to lack of separation between Hb A2 and Hb S or shoulders to the left of the Hb A2 peak. All were Hb SS and heterozygous for the alpha 3.7kb deletion, with 1 also positive for the triplicated alpha globin gene, anti 3.7kb. Four other samples with Hb A2 >7% also showed poor chromatography, but were insufficient for molecular testing.The results indicate that Hb A2values >5% were mainly due to co-existing alpha thalassaemia with 76% of those tested, positive for the 3.7kb deletion. Poor chromatography was also a contributor particularly at the higher Hb A2 levels. During the initial stages of the project air conditioning failure caused major temperature fluctuations on overnight runs, this problem was resolved, improving chromatography. One case of S/beta zero thalassaemia was detected confirming the presence in this population. The results suggest that the Hb A2 may be considered as a discriminator for S/beta thalassaemia screening in this setting, increasing the algorithm Hb A2 level to >6.0% may improve specificity and reduce the number of false positives, this warrants further investigation. Future aims of the project for children over 6 months of age, include initiating routine FBC analysis and testing parental samples as a cost effective means of confirming suspected cases. Disclosures:No relevant conflicts of interest to declare.

Prevalence of Hemoglobinopathy Disorders in Adult Patients Sent for Diagnosis of Anemia in Saudi Arabia

Hemoglobinopathies are a very heterogeneous group of congenital hemolytic anemia. Was to detect the prevalence of hemoglobinopathy disorders in adult patients sent for diagnosis of anemia by high-performance liquid chromatography techniques in Saudi Arabia. A total of 329 blood samples from suspected cases with an average age of 39±6.49 of both sexes (140 men and 189 women) were included in the study. A total of 118 (35.9%) patients were found to have a normal pattern of hemoglobin (Hb)-electrophoresis with a mean level of HbA (α(2)β(2)) (97.0%±0.40%), HbA2 (α(2)δ(2)) (2.72%±0.55%), and HbF (α(2)γ(2)) (0.59%±0.25%). One hundred twenty (36.5%) subjects were normal with iron deficiency masking the thalassemic trait (Hb: 8.71±1.7 g/dL, iron level: 3.62±2.7 μg/dL, total iron-binding capacity: 86.9±21.5 μg/dL). The remaining 91 (27.66%) patients showed different abnormal hemoglobin variants; 5 (1.5%) subjects had persistence of fetal HbF (7.12%±11.1%). Thirty-three (10.0%) subjects had β-thalassemia with a high level of HbA2 (>5.54%). Eleven (3.3%) had β-thalassemic/sickle cell disease. Twenty-nine (8.8%) had sickle cell trait with a level of HbS α(2)β(S)(2)<45%, and thirteen (4.0%) had sickle cell disease with a high level of HbS ≥45%. β-thalassemia and sickle cell anemia are the most common monogenic disorders in Saudi Arabia. This is a serious health threat to our nation, if it is allowed to continue without taking preventive measures.

Analysis of the molecular characterization of a Chinese pedigree with rare β thalassemia genotype

Objective To investigate the molecular characterization of a Chinese pedigree with rare β thalassemia genotype.Methods Phenotypic analysis was performed using standard hematological tests to measure red blood cell parameters, including RBC,Hb,MCV,MCH,MCHC and RDW.SPIFE automatic Hb agarose gel electrophoresis instrument was used to measure hemoglobin fraction Hb A,Hb A2 and Hb F.The alleles of β thalassemia mutation were determined by RDB assay, and then cloning and sequencing were performed to define the mutation sites.Results The proband and his father had typical microcytic hypochromic anemia with low MCV and MCH(79.8, 63.1 fl and 19.9, 20.9 pg, respectively) and high level of Hb A2 (5.66% and 5.60%, respectively).The proband′s mother had normal MCV and MCH. β thalassemia mutation analysis with RDB assay showed that the proband had thalassemia minor resulting from double mutations on one globin gene.One showed codons 41/42 (-TTCT) mutation and the other was CAP mutation from positions +40 to +43 in the promoter region.These two mutations were inherited from his father.The genotype of the proband and his father was β41/42、CAP/βA ,and the genotype of his mother was βA/βA.Conclusions It′s rare that double mutations occur on single β globin gene, with one mutation on CD41/42(-TTCT) and the other mutation from positions +40 to +43 relative to the mRNA cap site in the promoter region.The findings enrich knowledge of the mutation spectrum of β thalassemia. Key words: beta-Thalassemia; Pedigree; Globins; Mutation; Two-hybrid system techniques

Identification of a New Mutation on the β-Globin Gene: Codons 8/9 (+AGAA); GAG.AAG.TCT(Glu-Lys-Ser)>GAG. AAAGAAG, in a Patient From the North of France with a Phenotype of β-Thalassemia Minor

A 37-year-old man presented a slight debility. The hemogram showed a phenotype of β-thalassemia minor: Hb (13.1 g/dL), mean corpuscular volume (MCV) (62 fL) with low mean corpuscular hemoglobin (MCH) (20.8 pg), associated with a high level of Hb A2 of 5.3%. The serum ferritin level was 1,072 ng/mL. The sequencing of the mutated fragment revealed a duplication of four bases of codons 7/8 involving a shift in the open reading frame starting from codon 9 with a TGA stop codon at codon 23: codons 7/8/9 (+AGAA); GAG.AAG.TCT(Gly-Lys-Ser)>GAG.AAAGAAG. The human hemoglobin (Hb) instability tests were negative. The patient did not present the high iron Fe (HFE) mutation (C282Y, H63D). The same mutation was found in five other unrelated families (representing a total of 23 patients). All of their ancestors came from the north of France. This mutation has not been described before and could have its origins in the native populations of Northern France.

Study on the incidence of beta-Thalassemia and genotypes among children under 7 year-olds in Nanning, Liuzhou and Baise areas, Guangxi province

To conduct research of beta-Thalassemia incidence and genotypes on children below 7 years of age in Nanning, Liuzhou and Baise areas, Guangxi province. A total of 2261 children aged below 7 in Nanning, Liuzhou and Baise areas were studied. Venous blood was detected by routine blood test, hemoglobin analysis and beta-Thalassemia genotyping. Among 2261 samples, 125 showed high level of HbA2 and were diagnosed as beta-Thalassemia (5.53%). Genotypes of the patients were classified as: 59 cases with beta-globin gene condon (CD) 41-42 mutation, 33 cases CD17 mutation, 18 cases with TA TA box nt-28 mutation, 7 with IVS-II-654 mutation, 3 with CD43 mutation, 3 with HbE mutation, one with CD71-72 and TATA box nt-29 mutation, respectively. The genotyping frequencies of beta-Thalassemia were as follows: 47.20% for CD41-42 mutation, 26.40% for CD17 mutation, 14.40% for TATAbox nt-28 mutation, 5.60% for IVS-II-654 mutation, 2.40% for CD43 mutation, 2.40% for HbE mutation, 0.80% for CD71-72 mutation and TATAbox nt-29 mutation respectively. This study on children in the area with high incidence of beta-Thalassemia reflected the incidence and characteristics of genotypes in this area. Our data also provided evidence for the development of a program on genetic counseling and prevention for thalassemia.

A Rare Case Of Co-Existent Hb Q India-Beta Thalassemia Trait

Hb QIndia is a rare alpha chain variant and usually it presents in the heterozygous state. It's presence along with beta thalassemia trait again adds to its rarity. Such a rare entity can be diagnosed by careful screening in routine practice with the use of the techniques like Hb electrophoresis, Solubility test. We report a case of Hb Q in a concomitant presence of Beta thalassemia trait. CASE REPORT A 19 years old boy presented to us for the screening of the beta thalassemia minor and was found to have variant hemoglobin migrating in the position of the Hemoglobin S (HbS) on cellulose acetate electrophoresis at alkaline pH. The patient was asymptomatic without any significant past or family history and clinical examination. Automated cell counter used to determine the cell counts and indices showed the presence of thalassemic indices, whereas solubility test for sickling was negative (Table-1). Suspecting the presence of beta thalassemia trait, Hb electrophoresis at pH 8.4 was performed which showed presence of an abnormal band in the position of Hb S and duplicated bands of Hb A2 apart from normal band of Hb A, suggesting the presence of alpha chain variant in heterozygous state (Figure-1). Figure 1 Figure 1: Photograph showing the electrophoretic mobility of hemoglobin at pH 8.4 in propositus, father, mother, sister, and control of a known case of sickle cell trait. A Rare Case Of Co-Existent Hb Q India-Beta Thalassemia Trait 2 of 4 Figure 2 Table 1 Microcolumn chromatography using glycine-potassium cyanide developers showed the presence of high levels of Hb A2 in the thalassemic range (Table-2).

PREVALENCE AND HEMATOLOGICAL CHARACTERISTICS OF β-THALASSEMIA TRAIT IN GAZIANTEP URBAN AREA, TURKEY

Thalassemia is one of the most common hereditary disorders in the Mediterranean region and studies have shown that the prevalence of β-thalassemia trait is high in the southern part of Turkey. Gaziantep is a city located near this region and, therefore, the authors investigated the prevalence and hematological characteristics of the β-thalassemia traits in primary school students in Gaziantep. Sixty primary schools were selected from a list of all primary schools using a systematic sampling method. Data were collected by a face-to-face questionnaire. Osmotic fragility testing (OFT) using single-tube 0.36% NaCl solution was used for the screening of β-thalassemia. Students who were positive in regard to OFT went through a series of testing, including a complete blood count, serum ferritin levels, serum iron, and hemoglobin electroforesis. Chi-square test was used in statistical analysis. Of the 2439 students enrolled to the study from the selected 60 classrooms, 1353 (55.5%) were male and 1086 (44.5%) were female. The OFT was positive in 115 (4.7%) of the participants. CEA and confirmatory HPLC results of the students who were positive OFT indicated that 70 (60.8%) had normal results, 33(28.7%) showed high HbA2 levels, 7 (6.1%) showed high HbA2 and HbF levels, 5(5.2%) showed high HbA2 and Fe-deficiency anemia, and none showed increased HbF levels. The overall prevalence of β-thalassemia trait was 1.84%. No gender differentials and highest rates among the Kahramanmaras (3.5%) and Sanliurfa (1.7%) born students were the other significant findings of this study. Implementation of a routine carrier-screening program offering genetic counseling, prenatal diagnosis, and selective termination of affected fetuses would be a wise approach to eliminate this disease from the region.

High Hb A2 β-Thalassemia Due to a 468 bp Deletion in a Patient with Hb S/β-Thalassemia

We describe a case of Hb S/β-thalassemia (thal) involving a 468 bp deletion that removes the β-globin gene promoter but leaves the coding regions intact. This is the second report of this deletion, and our family study establishes that this deletion causes β0-thal with unusually high levels of Hb A2 and Hb F. As with other genotypes involving deletions of the 5′ region of the β-globin gene, our patient had a mild form of Hb S/β-thal.

Genetic insights into the clinical diversity of beta thalassaemia.

Genetic insights into the clinical diversity of beta thalassaemia.