Β-thalassemia Trait Research Articles

Genetic Regulation of Redox Balance in β-Thalassemia Trait

β-Thalassemia (β-thal) trait is a heterogeneous group of genetic defects leading to decreased β-globin production, ineffective erythropoiesis, and oxidative stress. The aim is to evaluate the cytoprotective response, at transcriptional and systemic levels, of the variations of global redox balance in β-thal trait patients. Sixty-six subjects (40 healthy and 26 with β-thal trait) were analyzed at the Universidad Nacional de Tucumán, Tucumán, Argentina, between 2016 and 2017. The following parameters were evaluated: complete blood count, iron status, hemoglobin (Hb) electrophoresis, Hb A2, thiobarbituric acid reactive species (TBARS), serum catalase (CAT), and superoxide dismutase (SOD) activity, FOXO3a, NRF2, SOD, PRDX2, CAT, interleukin-6 (IL-6), and tumor necrosis factor-α (TNF-α) gene expression. The β-thal trait group showed a decrease in Hb levels, MCV, and MCH with higher TBARS levels. The SOD activity was significantly increased by 32.0% in β-thal trait patients respect to the control group. Relative expression of NRF2 was 4.7-fold higher in β-thal trait than in the control group, while FOXO3a expression was similar in both groups. The SOD, PRDX2, and proinflammatory cytokines transcriptional expression was significantly upregulated in β-thal trait patients. This is the first study on the genetic regulation of redox balance in β-thal trait patients in which interesting modifications were observed in the transcript levels of some redox regulators that could be associated with changes in the erythrocyte proteome in this disorder. A better understanding of the pathophysiological mechanisms present in these heterozygous patients would allow adequate therapy in situations such as growth, pregnancy, or high performance sports, favoring a personalized treatment.

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.

Microcytic anemia in children: parallel screening for iron deficiency and thalassemia provides a useful opportunity for thalassemia prevention in low- and middle-income countries

Microcytic anemia in children is commonly attributed to iron deficiency without attempting to find the cause. Inadequate investigations to exclude hemoglobinopathies lead to missed opportunities for identification of thalassemia carriers. Here we aim to describe the relative contribution of iron deficiency and thalassemia to microcytic anemia in children. This hospital-based prospective study was conducted at the Colombo North Teaching Hospital, Ragama, Sri Lanka. All newly diagnosed patients with microcytic anemia were recruited and data were collected using an interviewer-administered questionnaire. Full blood count, blood film, serum ferritin, c-reactive protein, quantification of hemoglobin sub-types and α-globin genotype were performed using 4 ml of venous blood. A total of 104 children (Male- 60.5%) were recruited. Iron deficiency was the cause for anemia in 49% whilst 16% and 10% had α- and β-thalassemia trait respectively. Seven (6.7%) children had co-existing iron deficiency and thalassemia trait while two coinherited α- and β-thalassemia trait. Children with β-thalassemia trait had significantly higher red cell count and lower mean corpuscular volume compared to children with iron deficiency. However, none of the red cell parameters were significantly different between children with α-thalassemia trait and iron deficiency. Iron deficiency contributes only to half of children with microcytic anemia; one-fourth had thalassemia trait. Co-existence of iron deficiency and thalassemia trait or co-inheritance of α- and β-thalassemia trait were found in 9%. Parallel investigation of children with microcytic anemia to diagnose iron deficiency and thalassemia provides an opportunity to identify thalassemia carriers which is beneficial for thalassemia prevention.

Quantitative determination of HbA2 level in β-thalassemia trait by using Capillary Zone Electrophoresis in Balochistan; A comparative study

In Pakistan, β-thalassemia is considered as one of most typical genetic abnormality. Different countries like Itlay, France, and Greece have recognised thalassemia as preventive disorder of society. In Pakistan, since 1994 different efforts were made to control thalassemic epidemic. Inspite of this, there is no significant decline in occurrence of childbirth with transfusion dependent β-thalassemia incidents. In order to obtain fruitful results of general thalassemia eradication program nation wide, it is vital to evaluate β-thalassemia trait (BTT) by specific, low price, and accurate mechanism of diagnosis. So, this current research was carried out to decide the levels of HbA2 in samples by the use of Capillary Zone Electrophore and Cellulose Acetate Hemoglobin Electrophoresis.
 This comparative research was done in the four groups: i) Normal Individual having no sign or symptom of thalassemia ii) Patients having BTT i.e b-thalassemia trait iii) Patients having IDA i.e Iron Deficiency Anemia iv) Parents of β-thalassemia major child with iron deficiency anemia (BTT and IDA). It means that both parents are carrier of β-thalassemia not diagnosed yet.
 The level of HbA2 were estimated by the Cellulose Acetate Hemoglobin Electrophoresis and Capillary Zone Electrophoresis independently and then compared to design established results.
 Result: Both these methods have found to be correct for the patients having b-thalassemia trait (BTT) but in combined condition, cases of b-thalassemia trait (BTT) were failed to be analyzed by both these systems.
 Conclusion: As this technique is very easy, easily reachable and affordable. So, it is highly recommended for the diagnosis in the poor province like Balochistan in Pakistan. In thalassemia prevention, it plays a vital role.

Prevalence of Hemoglobinopathies (β-Thalassemia and Sickle Cell Trait) in the Adult Population of Al Majma’ah, Saudi Arabia

Despite the high prevalence of hemoglobinopathies in Saudi Arabia, the prevalence data in some regions are lacking. Updating the epidemiological survey of hemoglobinopathies at regular intervals is necessary to develop effective prevention and control strategies. Therefore, the primary aim of this study was to determine the prevalence of selected hemoglobinopathies in Saudi adults attending premarital screening at the King Khaled General Hospital (KKGH), Al Majma’ah, Saudi Arabia. The current retrospective study was approved by the Central Institutional Review Board (IRB) of the Ministry of Health (with central IRB log #2019-0039E) and was carried out at the above hospital. The data of the premarital couples, who attended the premarital screening center at KKGH from 1 October 2016 to 30 September 2019, was included in this study. A cation exchange high performance liquid chromatography (HPLC) system was used for screening of the selected hemoglobinopathies. In total, 3755 cases including 1953 (52.01%) males and 1802 (47.99%) females, were screened for hemoglobinopathies. Abnormal hemoglobin (Hb) fractions were observed in 38 (1.01%) cases. The prevalence of β-thalassemia (β-thal) trait was 0.69% (26/3755) and that of sickle cell trait 0.32% (12/3755). Our results showed that the prevalence of β-thal trait is higher than that of sickle cell trait in the adult population of Al Majma’ah. Further comprehensive programs should be carried out to determine the prevalence of hemoglobinopathies in various provinces and cities of Saudi Arabia and other countries. This will help to maintain the updated records of the disease incidence for improving the control measures.

Utility of Blood Indices and Parameters for Differentiating Iron Deficiency Anaemia and Β-Thalassemia Trait by Calculating Various Discriminant Functions

BACKGROUND: There are various causes of hypochromic microcytic anaemia. Among these β-thalassemia trait and iron deficiency anaemia are much more common in developing country like India. Various parameters obtained on automated haematology analyser by calculating discriminant functions to differentiate iron deficiency anaemia and β thalassemia trait becomes easy and cost effective. Objective: To differentiate iron deficiency anaemia and β-thalassemia trait by blood indices, red cell distribution width and various discriminant functions. Materials and Methods: This study was carried out in the pathology department of AMC MET medical college, L.G.Hospital, Maninagar, Ahmedabad. We had studied 100 cases of differentiating Iron deficiency Anaemia and β-Thalassaemia trait from patient’s case records and laboratory reports irrespective of age and sex over a period of one year (January 2019 to December 2019). Tests for serum iron and ferritin were carried out in individuals showing low hemoglobin (Hb). All the selected subjects’ samples were subjected to blood morphology, comparison of MCV, RBC count, RDW, RDWI, SI, GI and MI. Results: Out of 100 cases seventy five were diagnosed having IDA, whereas twenty five were having β-TT. The RBC count was higher, and MCV was much lower in βTT as compared to IDA. Both groups were subjected to RDW,RDWI, SI, MI and GI. Conclusion: Among various discriminant function calculated from different haematological parameters and blood indices Mentzer index and Srivasta index are more sensitive and specific for differentiating IDA and β-TT.

Hereditary spherocytosis overlooked for 7 years in a pediatric patient with β-thalassemia trait and novel compound heterozygous mutations of SPTA1 gene

ABSTRACT Objectives: We aimed to determine the clinical and genetic characteristics of a boy diagnosed with the β-thalassemia trait. He also had hereditary spherocytosis (HS) that had been overlooked for 7 years. Methods: Blood samples collected from the proband and his family were assessed by laboratory tests, and next-generation sequencing (NGS) and Sanger sequencing. Results: The β-thalassemia trait was complicated with HS in the proband. Compound heterozygous mutations of the Spectrin Alpha, Erythrocytic 1 (SPTA1) gene, c.83G > A and c.190G > A in the proband were inherited from his mother and father, respectively, and he also had the heterozygous c.126_129delCTTT mutation in the Hemoglobin Subunit Beta (HBB) gene. The c.190G > A mutation has not yet been added to the Human Gene Mutation Database (HGMD®). The heterozygous HBB c.126_129delCTTT mutation was inherited from his mother, and his older brother also had this mutation. Conclusion: Compared with other patients with either HS or β-thalassemia, this proband with both HS and the β-thalassemia trait had very complicated laboratory findings, which resulted in HS being overlooked for 7 years. Genetic testing is invaluable for the differential diagnosis of hereditary anemias with overlapping clinical features.

A demographic prevalence of β Thalassemia carrier and other hemoglobinopathies in adolescent of Tharu population.

Background and Aims:Hemoglobinopathies and thalassemias are the commonest single gene disorders in India. In Terai region of India, Hemoglobinopathies and thalassemias are the most common in the Tharu community. Therefore, in this study, we aim to evaluate the Hb variant analysis of hemoglobinopathies and thalassemias in a Tharu population in Lakhimpur Kheri Districts of Uttar Pradesh, India.Materials and Methods:Total 493 individuals were recruited in this study. The demographic details and blood samples were collected from different location at Kheri district during mega health camp. Hb variant analysis was performed by high performance liquid chromatography (HPLC) system beta thalassemia short program in BIO-RAD VARIANT.Results:Out of 493, 108 (21.9%) individual suffers with abnormal haemoglobinopathies. In which β-thalassemia trait is the commonest haemoglobinopathy (12.98%), followed by HbE trait (7.50%), and compound heterozygous HbS/β-Thalassemia trait (1.42%) in overall population. The HbF was significantly greater in HbS heterozygous (1.45 ± 1.41), whereas mean HbA2 was significantly greater in β-Thalassemia trait (5.17 ± 1.36).Conclusion:The high incidence of hemoglobinopathies and thalassemias were observed in Tharu community in Lakhimpur Kheri districts of Uttar Pradesh, Indian.

Hemoglobin Disorders Among Anemic Patients: a Cross-Sectional Study from Jeddah City, Western Saudi Arabia.

Hemoglobinopathies and thalassemia are defined as a group of inherited blood disorders characterized by a variable degree of anemia with a wide spectrum of clinical symptoms. They are commonly found in the Mediterranean area, sub-Sahara Africa, Middle East, Central India, and Southeast Asia with an estimation of 400,000 babies born annually with serious hemoglobinopathies. Of those, 90% of the births occur in underdevel-oped or developing countries. This study was undertaken to investigate the prevalence of hemoglobin disorders among anemic patients who visited a tertiary care setting represented by King Abdulaziz University Hospital. This is a cross sectional study which investigated blood samples from 668 anemic patients for possible causes of anemia. This investigation involved the use of complete blood count, hemoglobin separation using capillary electrophoresis, and measurement of nutritional elements commonly investigated for anemia. We found that the frequency of different types of hemoglobinopathies and thalassemia among the subjects were as follow; normal (HbAA) 439 (65.7%); Sickle Cell Trait (HbAS) 65 (9.7%); Sickle Cell Anemia (HbSS) 63 (9.4%); β-thalassemia trait 48 (7.2%); Hb S/β 27 (4.0%); HbH 7 (1.0%); HbE 6 (0.9%); beta-thalassemia major 6 (0.9%); Hb E/beta-thalassemia 4 (0.6%); HbC 1 (0.1%); HbD 1 (0.1%) and HbSC 1 (0.1%). The findings of this study emphasize the necessity of increasing public health education, neonatal and adult screening programs, as well as nutritional guidance and plans to start the eradication of this burden.

A Novel εγδβ-Thalassemia Deletion Associated with Severe Anemia at Birth and a β-Thalassemia Intermedia Phenotype Later in Life in Three Generations of a Greek Family

We describe a novel deletion causing heterozygous εγδβ-thalassemia (εγδβ-thal) across three generations of a Greek family. The Greek deletion is about 72 kb in length, spanning from the hypersensitive site 4 (HS4) in the locus control region (LCR) to the 3' end of the β-globin gene, thus encompassing the entire β-globin gene cluster. The deletion caused severe but transient neonatal anemia and a non transfusion-dependent chronic hemolytic anemia state later in life, resembling mild β-thalassemia intermedia (β-TI) rather than β-thalassemia (β-thal) trait, as had been previously reported. Apart from the presentation of clinical and laboratory characteristics, the challenges involving clinical management are also discussed.

An Insight on Beta Zero (β0) Southeast Asian Deletion (βSEA); Is it a β0-Thalassemia or Hereditary Persistence of Fetal Hemoglobin (HPFH)

"An Insight on Beta Zero (β0) Southeast Asian Deletion (βSEA); Is it a β0-Thalassemia or Hereditary Persistence of Fetal Hemoglobin (HPFH)." Hemoglobin, 43(6), p. 362

Anemia Prevalence after Iron Supplementation among Pregnant Women in Midwifes Practice of Primary Health Care Facilities in Eastern Indonesia.

Background Iron deficiency anemia (IDA) in pregnant women is common, and iron supplementation is given during pregnancy to reduce birth complication. This study aimed to explore the prevalence of anemia and type of anemia after iron supplementation among pregnant women in the eastern part of Indonesia. Methods A cross-sectional study design was conducted between January and March 2019 in three Primary Health Care (PHC) facilities at Kupang, West Timor. After consent, pregnant women who had taken their iron supplementation for at least 3 months were asked for iron pills intake by using a self-designed questionnaire and by counting the pills leftover. Complete blood count examination was performed, and the type of anemia was assessed using Shine and Lal index (SLI; MCV ∗ MCV ∗ MCH/100) to determine whether anemia was due to iron deficiency or β-thalassemia trait (β-TT). In a subset of iron tablets distributed in the PHCs, Fe-concentration was measured. Results Of 102 pregnant women included, only 25.5% had taken the pills with a pill count of >80%. Interestingly, Fe-concentration in the pills from three different PHC facilities varied between 75% and 100%. After iron supplementation, however, anemia was detected in 34.3%, and based on SLI, 14.7% was suspected because of iron deficiency and 19.6% was suspective of β-TT. Of note, nonanemic pregnant women (17.6%) had also low SLI, suggesting β-TT or other hemoglobinopathies. Conclusion Assessment of Shine and Lal index as the first step to screen the type of anemia in pregnant women from a limited area is of potential value, especially because Indonesia is located in the thalassemia belt area. An integrative approach and counseling among pregnant women with β-TT and their partners will increase thalassemia awareness and optimal birth management.

Laboratory Values in Iron Deficiency Anemia and β-Thalassemia Trait

Research Article| October 01 2019 Laboratory Values in Iron Deficiency Anemia and β-Thalassemia Trait AAP Grand Rounds (2019) 42 (4): 46. https://doi.org/10.1542/gr.42-4-46 Views Icon Views Article contents Figures & tables Video Audio Supplementary Data Peer Review Share Icon Share Twitter LinkedIn Tools Icon Tools Get Permissions Cite Icon Cite Search Site Citation Laboratory Values in Iron Deficiency Anemia and β-Thalassemia Trait. AAP Grand Rounds October 2019; 42 (4): 46. https://doi.org/10.1542/gr.42-4-46 Download citation file: Ris (Zotero) Reference Manager EasyBib Bookends Mendeley Papers EndNote RefWorks BibTex toolbar search nav search search input Search input auto suggest search filter All PublicationsAll JournalsAAP Grand RoundsPediatricsHospital PediatricsPediatrics In ReviewNeoReviewsAAP NewsAll AAP Sites Search Advanced Search Topics: iron deficiency anemia, reference values, thalassemia Source: Aydogan G, Keskin S, Akici F, et al. Causes of hypochromic microcytic anemia in children and evaluation of laboratory parameters in the differentiation. J Pediatr Hematol Oncol. 2019; 41(4): e221– e223; doi: https://doi.org/10.1097/MPH.0000000000001382Google Scholar Investigators from Turkey conducted a prospective cohort study in children with hypochromic microcytic anemia to assess the frequency of the diagnoses of iron deficiency anemia (IDA) and β-thalassemia trait (TT), as well as how blood cell count parameters differed between them. Children 6 months to adolescents 18 years old who were referred to the study institution for outpatient evaluation of hypochromic microcytic anemia were included. Those with a known hematologic diagnosis or a chronic disease were excluded. Complete blood cell counts, serum iron levels, total iron-binding capacity (TIBC), ferritin levels, transferrin levels, and a peripheral smear were obtained from all participants. Hypochromic microcytic... You do not currently have access to this content.

A β-Thalassemia Trait with Two Mutations in Cis in a Chinese Family

A female of Chinese origin carried the codon 43 (G>T) (HBB: c.130G > T) and codons 71/72 (+A) (HBB: c.216_217insA) mutations of the β-globin gene in cis, identified during prenatal thalassemia screening. The double in cis mutations were inherited from her mother. Both of the two carriers behave as a traditional heterozygote for β-thalassemia (β-thal) with microcytosis and a high Hb A2 level. This case report indicates that the possibility of multiple mutations in cis in a fetus with thalassemia trait has to be considered in a prenatal screening program.

A "One-Stop" Screening Protocol for Haemoglobinopathy Traits and Iron Deficiency in Sri Lanka.

Introduction: The high frequencies of carriers of severe haemoglobinopathies and of iron deficiency in Southeast Asia require reliable and affordable tests to improve on current screening procedures.Objectives: We evaluate a “one stop” approach using the THALCON dichlorophenolindophenol (DCIP) and one-tube osmotic fragility (OF) tests and measurement of Zinc Protoporphyrin (ZPP) to detect and distinguish HbE and β-thalassaemia traits from iron deficiency. We compare findings with current screening practice in Sri Lanka that relies on the identification of low mean red cell volume and/or mean red cell hemoglobin for this purpose.Methods: Between November 2017 and May 2018, we undertook a cross-sectional survey of secondary school students in Gampaha district, Sri Lanka. The THALCON–DCIP and OF tests were compared to capillary electrophoresis (CE), used as a gold standard to detect haemoglobinopathies. ZPP was measured in whole blood. Plasma ferritin and C-reactive protein (CRP) were measured in students with a raised ZPP concentration.Results: We collected venous blood samples from 1,324/1,332 (99.4%) students. The median age of the students was 17 (IQR 16–18) years, all were Sinhalese and 814/1,324 (61.5%) were female. CE identified 3 students with HbE trait and 26 students with β-thalassaemia trait. The THALCON–DCIP test was positive only in the 3 students with HbE (sensitivity 100%, 95% CI 29.2–100.0; specificity 100%, 95% CI 99.7–100.0). The THALCON–OF test identified all 26 students with β-thalassaemia trait (sensitivity = 100%, 95% CI 86.8–100.0) and 287 students with a normal CE result (specificity = 77.9%; 95% CI 75.5–80.1). It was also positive in 2/3 (66.7%) students with HbE trait. Iron deficiency (ZPP > 70 μmol/mol heme) was present in 118/1,240 (9.5%) students with a normal hemoglobin genotype, all of whom had plasma ferritin <15 ng/ml and CRP <5 mg/L.Conclusion: This one–stop approach offers reliable and affordable population screening for both haemoglobinopathy traits and iron deficiency in resource-limited settings where these conditions are common and ensures that iron supplements are targeted only to those who require them. Further work is warranted to refine the OF test to reduce the number of false positive results.

Diagnosis of Hemoglobinopathy and β-Thalassemia by 21 Tesla Fourier Transform Ion Cyclotron Resonance Mass Spectrometry and Tandem Mass Spectrometry of Hemoglobin from Blood.

Hemoglobinopathies and thalassemias are the most common genetically determined disorders. Current screening methods include cation-exchange HPLC and electrophoresis, the results of which can be ambiguous because of limited resolving power. Subsequently, laborious genetic testing is required for confirmation. We performed a top-down tandem mass spectrometry (MS/MS) approach with a fast data acquisition (3 min), ultrahigh mass accuracy, and extensive residue cleavage by use of positive electrospray ionization 21 Tesla Fourier transform ion cyclotron resonance-tandem mass spectrometry (21 T FT-ICR MS/MS) for hemoglobin (Hb) variant de novo sequencing and β-thalassemia diagnosis. We correctly identified all Hb variants in blind analysis of 18 samples, including the first characterization of homozygous Hb Himeji variant. In addition, an Hb heterozygous variant with isotopologue mass spacing as small as 0.0194 Da (Hb AD) was resolved in both precursor ion mass spectrum (MS1) and product ion mass spectrum (MS2). In blind analysis, we also observed that the abundance ratio between intact δ and β subunits (δ/β) or the abundance ratio between intact δ and α subunits (δ/α) could serve to diagnose β-thalassemia trait caused by a mutation in 1 HBB gene. We found that 21 T FT-ICR MS/MS provides a benchmark for top-down MS/MS analysis of blood Hb. The present method has the potential to be translated to lower resolving power mass spectrometers (lower field FT-ICR mass spectrometry and Orbitrap) for Hb variant analysis (by MS1 and MS2) and β-thalassemia diagnosis (MS1).

Impact of β-thalassemia trait carrier state on inflammatory status in patients with newly diagnosed hypertension.

B-thalassemia carrier state or thalassemia minor confers cardiovascular protection through favorable lipidemic and blood pressure profile. However, its impact on inflammatory status-a common denominator of the above conditions-has not been addressed. We investigated a wide range of inflammatory markers [white blood cell (WBC) count, homocysteine, C-reactive protein (CRP), serum amyloid A (SAA), fibrinogen, plasminogen, fibronectin, plasminogen activator inhibitor-1 (PAI-1), and uric acid] in a large cohort of 15 805 newly diagnosed hypertensive patients (8299 men, 7506 women); 626 of them (4.0%) had thalassemia minor. The levels of WBC, homocysteine, CRP, SAA, fibrinogen, and PAI-1 were significantly lower in thalassemia minor patients, but not of plasminogen, fibronectin, and uric acid. In multivariate linear regression analyses, the lower values of WBC (<0.001), CRP (<0.001), homocysteine (<0.001), fibrinogen (<0.001), and PAI-1 (0.008), but not of SAA, were independently associated with thalassemia minor. The interaction between thalassemia minor and body mass index had a significant impact only on WBC and CRP (P for the interaction 0.010 and 0.005, respectively), whereas the interaction between thalassemia minor and sex had a significant impact only on fibrinogen (P for the interaction 0.007). Thalassemia minor is followed by a favorable inflammatory profile that may contribute to the overall better cardiovascular health of the carriers.

A Novel Human β-Globin Gene Variant [Hb London-Ontario, HBB: c.332T>G] is Associated with Transfusion-Dependent Anemia in a Patient with a Hemoglobin Electrophoresis Pattern Consistent with β-Thalassemia Trait

We present the case of a novel β-globin gene variant associated with early-onset transfusion-dependent anemia compatible with a β-thalassemia major (β-TM) phenotype in a patient of British descent. As a child, our patient developed chronic symptomatic anemia with hemoglobin (Hb) nadirs of 3.0 g/dL. She started receiving occasional transfusions by the age of 13 years and became transfusion-dependent by the age of 32 years. Work-up performed at our center showed a Hb electrophoresis compatible with β-thalassemia (β-thal) trait. Polymerase chain reaction (PCR) of the β-globin gene detected a novel mutation situated at codon 110 (CTG). This missense mutation led to a substitution of the thymine nucleotide (nt) base for guanine (CGG) at position 332 (HBB: c.332T>G). We have named this new mutation Hb London-Ontario. The majority of previously described dominant allelic mutations of the β-globin gene led to a β-thal intermedia (β-TI) phenotype. The heterozygous mutation which was detected in our patients is unique at it leads to a more severe β-TM phenotype. We suspect this is a de novo mutation of which the mother of our patient, who was reported to have a form of thalassemia, was the proband.

A Case of Hereditary Spherocytosis Caused by a Novel Homozygous Mutation in the SPTB Gene Misdiagnosed as β-Thalassemia Intermedia Due to a KLF1 Gene Mutation

We report a rare case of hereditary spherocytosis (HS) and hereditary persistence of fetal hemoglobin (Hb) (HPFH) complicated with a β-thalassemia (β-thal) trait and a Krüppel-like factor 1 (KLF1) gene mutation misdiagnosed as β-thal intermedia (β-TI) due to a high percentage of Hb F. The proband presented with pale skin, jaundice and splenomegaly. Analysis of the thalassemia gene indicated βcodon 17/βA (HBB: c.52A>T), while Hb analysis showed significantly increased Hb F levels. The proband was diagnosed to carry β-TI, and a blood transfusion regimen together with iron chelation treatment was recommended. Due to the difference between the phenotype and genotype, next generation sequencing (NGS) was performed and the proband was found to carry a homozygous mutation on the SPTB gene combined with a heterozygous mutation in KLF1. An eosin-5-maleimide binding test (EMA-BT) showed that the mean fluorescence intensity decreased by 47.1%. The proband was finally diagnosed with HS and HPFH complicated with a β-thal trait and the high percentage of Hb F was believed to be ascribed to the KLF1 gene mutation, which is frequent in areas where thalassemia is prevalent. For patients with a β gene mutation accompanying significantly high percentage of Hb F, the diagnosis of β-TI could be warranted, and the influence of the KLF1 gene mutation should be carefully excluded to avoid misdiagnosis of other types of hereditary hemolytic diseases.

Simple Red Cell Indices in Screening and Discrimination of Iron Deficiency Anemia and Beta Thalassemia Trait in Egyptian Patients

Background: The most common causes of microcytic hypochromic anemia are iron deficiency anemia (IDA) and the beta-thalassemia trait (β-TT). The aim of the work is to compare the validity of the various simple indices to differentiate between iron deficiency anemia and β-thalassemia trait. Subjects and methods: A total of 2000 individuals were screened, by complete blood picture, measurement of serum iron, serum ferritin and hemoglobin separation; 224 patients were detected as having hypochromia and microcytosis. Among them 166 cases were IDA and 58 cases were β-TT. We calculated 11 discrimination indices. The number of correctly identified cases were determined, sensitivity, specificity, positive and negative predictive value and Youden’s index (YI) of each discrimination index was calculated. Results: The percentage of correctly diagnosed patients is highest for Matos and Carvalho index (MCI) (95.5%) which is closely followed by Red cell distribution width index (RDWI) (93.7%). The third high index was Green and King (GKI) (91.9%). Sensitivity, specificity of MCI for detection of IDA was found 98.8%, 87.9% respectively. For β-TT, sensitivity and specificity was found 86.2% and 98.8% respectively. The YI of MCI was found 85.9%. It is followed by RDWI; its sensitivity and specificity for detection of IDA was found 97.6%, 85.3%. For β-TT, sensitivity and specificity was found 82.7% and 97.6% respectively. The YI of RDWI was 81.6%. Conclusion: Matos and Carvalho index and RDWI are easily available automated cell-count-based indices coming out as good discriminator between IDA and β-TT in our study.