Thalassemia – Increasingly Frequent Cause of Microcytic Anemias in Children in Poland

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5184-5184
Author(s):  
Katarzyna Albrecht ◽  
Anna Adamowicz-Salach ◽  
Beata Burzynska ◽  
Katarzyna Pawelec ◽  
Michal Matysiak
Keyword(s):  
Conflicts Of Interest ◽  
Iron Status ◽  
Microcytic Anemia ◽  
Diagnostic Methods ◽  
Beta Thalassemia ◽  
Globin Chains ◽  
Thalassemia Minor ◽  
Genetically Determined ◽  
Molecular Biological Techniques

Abstract Abstract 5184 Thalassemias are a group of genetically determined hemolytic anemias related to disturbed synthesis of globin chains, and are classified as quantitative hemoglobinopathies. We would like to present our experience in diagnosis of thalassemia in children as an increasingly frequent cause of microcytic anemias as well as to point out that it is the cause of microcytic anemia in Poland. Between 2005–2012 we established the diagnosis of thalassemia minor in 94 children of Polish origin, referred to the Department of Pediatrics, Hematology and Oncology, Medical University of Warsaw. At admission all patients presented microcytosis, erythrocytosis, hypochromia and normal or elevated iron status. Most of them had long-lasting uneffective iron therapy in anamnesis. Their age ranged from 3 to 17 years. The group consisted of 40 girls and 54 boys. Routinely employed diagnostic methods, including blood morphology, determination of iron and ferritin, electrophoretic separation of hemoglobins, determination of HgbA2 and HgbF, as applied in all cases, often turn out to be insufficient to diagnose thalassemia, substantiating the need to use modern molecular biological techniques. Thalassemia alfa was diagnosed in 9 children in whom we detected deletion α 3, 7 using molecular biological techniques. In 2 children coexistence of both thalassemia alfa and beta was established. Both children presented macrocytosis and normal range of haemoglobin and red blood cells count. The molecular biological techniques used in both cases identified deletion α 3, 7 characteristic for alfa thalassemia, and Hb Koln (Codon GTC>ATG) and Del 4, 2 (Taq1) characteristic for beta thalassemia. In the remaining 83 patients we made the diagnosis of thalassemia beta. The diagnosis was possible after the evaluation of Hgb A2 and F levels. In 24 cases we managed to performed molecular biological techniques, identifying mutation IVS I-6 (T>C) as the most frequent. Generally associated with the Mediterranean Basin, thalassemia is, however, more and more often diagnosed in Poland. This is due to the international human traffic. Growing availability of diagnostic tests, like molecular biological techniques, especially useful in equivocal cases, is also important. The amplification of diagnostic possibilities by genetic tests in the future may be useful in detection of genetic mutations responsible for thalassemia and characteristic for Polish population. Disclosures: No relevant conflicts of interest to declare.

Genetic Heterogeneity of Alpha - and Beta - Globin Mutations in a German Multiethnic Population Group

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 5185-5185
Author(s):  
Regine Grosse ◽  
Florian Oyen ◽  
Belinda Weber ◽  
Reinhard Schneppenheim
Keyword(s):  
Genetic Counseling ◽  
Conflicts Of Interest ◽  
Beta Thalassemia ◽  
Compound Heterozygous ◽  
Beta Globin ◽  
Globin Chain ◽  
Globin Chains ◽  
Hemoglobin C ◽  
Thalassemia Minor ◽  
Alpha Globin

Abstract Abstract 5185 Thalassemia syndromes are among the most common hereditary diseases worldwide and are widespread throughout the Mediterranean Region, Africa, the Middle East, India, Burma, the Southeast Asia and Indonesia. Similarly, hemoglobinopathies are common in different ethnic groups and mixed syndromes of Thalassemia and hemoglobinopathies exist. In this retrospective study we report the number and type of Thalassemia mutations and their combination with hemoglobinopathies detected mostly in individuals with a migration background now living in Germany. DNA samples were analyzed by polymerase chain reaction (PCR) and direct DNA-sequencing and additionally by multiplex ligation-dependent amplification (MRC-HOLLAND MLPA®). Mutations in one or both beta-globin chains were found in 77 patients. Most of these mutations were beta Thalassemia mutations, n=41 (Thalassemia minor n=33, Thalassemia major/intermedia n=7, homozygous Quin-Hai Hemoglobinopathy n=1). In 34 samples we found the hemoglobin S single base mutation c. 20A>T p. E7V, either alone or in combination with a hemoglobin C mutation c. 19G>A p. E7K or beta Thalassemia mutation (HbAS n=14, HbSS n=12, HbSC n=6, HbSThal n=2). In two patients we found only the hemoglobin C mutation by itself (HbAC n=1, HbCC n=1). In 52 samples we found mutations on the alpha-globin chains, most often the 3. 7KB deletion (n=27), followed by the SEA (n=4), the 20. 5 KB deletion (n=4), the 4. 2 KB deletion (n=4), the Dutch deletion (n=3) and alpha triplication (n=3). Two of the remaining seven samples showed new alpha Thalassemia mutations which have not been described yet. In an additional 34 DNA samples we found a combination of alpha- and beta-globin chain changes. In 4 of these samples we detected new mutations in the alpha-globin chains. The prevalence of mutations in the alpha- and beta-globin chains varies greatly because of a complex ethnic structure of our patients. Changes of the alpha-globin chains could not be safely detected by hemoglobin-electrophoresis. These situations are very important for genetic counseling in a population in which consanguineous marriages are common. Furthermore, alpha-globin mutations are genetic modifiers for beta Thalassemia and sickle cell disease and will influence the phenotype of beta-globin chain mutations. Patients with a compound heterozygous mutation for beta Thalassemia will probably not be detected by hemoglobin-electrophoresis alone, as in milder forms and early childhood the hemoglobin is not severely decreased and hemoglobin electrophoresis may be misinterpreted for Thalassemia minor. Our findings underline the heterogeneity of beta-globin and alpha-globin chain mutations and the importance of hematological and molecular analyses in the diagnosis and genetic counseling. Disclosures: No relevant conflicts of interest to declare.

A New Mutation Of The ALAS2 Gene In a Chinese Family With X-linked

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 4674-4674
Author(s):  
Rui Cui ◽  
Guoqing Zhu ◽  
Zefeng Xu ◽  
Yue Zhang ◽  
Gang Huang ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Iron Status ◽  
Family Members ◽  
Iron Chelation ◽  
Microcytic Anemia ◽  
Chinese Family ◽  
Sideroblastic Anemia ◽  
Distribution Width ◽  
Aminolevulinate Synthase ◽  
Status Data

X-linked sideroblastic anemia (XLSA; OMIM 301300) is one of the most common inherited sideroblastic anemia, which results from mutations in the erythroid-specific isozyme of 5-aminolevulinate synthase. An amino acid (AA) substitution for arginine at the 452 AA position of the ALAS2 protein is the most frequent mutation, which has been found in approximately one-quarter of patients with XLSA. Here we first report a 3-generation pedigree including 10 individuals with a K156E substitution in ALAS2 gene in China. A 34 year-old man, complained with a microcytic anemia (hemoglobin (Hb) 84 g/dl, MCV 63.8 fl and MCH 16.5pg), increased ferritin serum (3123ng/ml) and transferrin sat (93%), and dyserythropoiesis with 50% of ring sideroblasts (RS) in BM. A diagnosis of XLSA was made. On treatment with 300mg/d pyridoxine and iron chelation therapy with deferoxamine allowed a correction of anemia and reduction of the S-ferritin (1096 ng/ml) in the proband. The peripheral blood samples had been extracted from proband and his family members. All exons containing exon-intron boundaries of ALAS2, SLC25A38 and GLRX5, the promoter region and intron 8 of ALAS2 were amplified and directly sequenced. He is a heterozygous for ALAS2 K156E substituion. The pedigree of the proband's family is shown in Figure 1, while hematologic and iron status data for the family members are reported in Table 1. All 4 heterozygous females from this family showed marginally increased red-cell distribution width (RDW) without phenotypic expression.Figure 1The pedigree of the probandFigure 1. The pedigree of the probandTable1Clinical and hematological features of the pedigreeSubjectSex/age,yHb g/dLMCV fLRDW%Ferritin μg/LALAS2I-1F/6811585.221.4136.7+II-1F/381288912.532.89-II-2M/348463.832.83123+II-3F/3213691.914.816.8-III-1M/2015288.212.1123.6-III-2F/1812384.813.321.84-III-3M/71449212.951.9-III-4F/101338513.716.8+III-5F/812681.418.831.2- In summary, this is a novel K156E substitution in ALAS2 gene discovered in a 3-generation pedigree in China. Furthermore, early diagnosis of XLSA allows preventing the complications of the iron overload by chelators or by iterative phlebotomies. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Uncovering the Role of Heme Oxygenase 1 in the Pathophysiology of β-Thalassemia

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1364-1364 ◽  
Author(s):  
Daniel Garcia-Santos ◽  
Marc Mikhael ◽  
Monika Horvathova ◽  
Prem Ponka
Keyword(s):  
Heme Oxygenase ◽  
Conflicts Of Interest ◽  
Fetal Liver ◽  
Thalassemia Major ◽  
Severe Form ◽  
Cellular Damage ◽  
Heme Oxygenase 1 ◽  
Globin Chains ◽  
Thalassemia Minor ◽  
Free Heme

Abstract Thalassemias are a heterogeneous group of red blood cell disorders ranging from a clinically severe phenotype requiring life-saving transfusions (thalassemia major) to a relatively moderate symptomatic disorder, sometimes requiring transfusions (thalassemia intermedia). Thalassemia minor, the least severe form of the disorder, is characterized by minimal to mild symptoms. While thalassemia minor and intermedia are vastly more prevalent than thalassemia major, the latter is often fatal when not treated. Though considered a major cause of morbidity and mortality worldwide, there is still no universally available cure for this severe form of thalassemia. A reason for this is at least in part due to the lack of full understanding of pathophsyiology of thalassemia. The underlying cause of pathology in thalassemia is the premature apoptotic destruction of erythroblasts causing ineffective erythropoeisis. Normally, the assembly of adult hemoglobin (consisting of a tetramer of two α- and two β-globin chains) features a very tight coordination of α- and β-globin chain synthesis. However, in β-thalassemia, β-globin synthesis is decelerated causing α-globin accumulation; while in α-thalassemia the opposite scenario occurs. Unpaired globin chains that accumulate in thalassemic erythroblasts are bound to heme. In addition, in β-thalassemia an erythroid specific protease destroys excess α-globin chains, likely leading to the generation of a pool of “free” heme in erythroblasts. “Free” heme is toxic, but this toxicity will likely be augmented, if heme oxygenase 1 (HO-1) can release iron from heme. To date, virtually no information about the expression of HO-1 in erythroblasts has been produced; however, we have recently provided unequivocal evidence that this enzyme is present in several model erythroid cells1. Based on this novel and important finding, we hypothesize that in β-thalassemic erythroblasts HO-1 mediated release of iron from heme is the major culprit responsible for cellular damage. To test this hypothesis we exploited the mouse model of β-thalassemia, th3/th3. Thus far, our data indicates that HO-1 expression is increased in liver, spleen and kidney of β-thalassemic mice compared to wild type mice. Importantly, we observed that Epo-mediated erythroid differentiation of fetal liver (FL) cells isolated from β-thalassemic fetuses, display increased levels of HO-1 at mRNA and protein levels as well as decreased phosphorylated eiF2-α. Ferritin levels are also increased in these cells suggesting increased heme catabolism and iron release. Altogether, these results indicate that β-thalassemic erythroblasts have inappropriately high levels of unbound heme that is continuously degraded by HO-1. Further research is needed to determine whether HO-1 liberated iron is responsible for the damage of β-thalassemic erythroblasts. 1Garcia-Santos D, et al. Heme oxygenase 1 is expressed in murine erythroid cells where it controls the level of regulatory heme. Blood 123 (14): 2269-77, 2014. Disclosures No relevant conflicts of interest to declare.

scholarly journals Evaluation of Erythroferrone, Hepcidin, and Iron Overload Status in Iraqi Transfusion-dependent β-Thalassemia Major Patients

2019 ◽  
Author(s):  
Hasan Smesam ◽  
Hasan Qazmooz ◽  
Sareh Arjmand ◽  
Hussein Kadhem Al-Hakeim ◽  
Seyed Omid Ranaei‐Siadat,
Keyword(s):  
Iron Overload ◽  
Iron Status ◽  
Iron Chelation ◽  
Fold Increase ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Control Group ◽  
Beta Globin ◽  
Beta Thalassemia Major ◽  
Globin Chains

Beta thalassemia major (β-TM) disorder characterized by the lack, or severe reduction in the production of hemoglobin β-globin chains. The standard protocol for the management of β-TM is blood transfusion and iron chelation therapy to reduce the iron overload state. The present study aimed to investigate the relationships between two iron regulatory hormones, hepcidin (HEPC) and erythroferrone (ERFE) levels and iron status parameters (ISPs) in Iraqi patients with β-TM. ISPs and hormones were measured in sixty patients and compared with thirty healthy controls. The results indicated significant changes in different iron status parameters, while ferritin (FRT) with the ~11 fold increase showed the most change. Significant reduction in HEPC and increase in ERFE levels were detected in patients as compared to the control group, while no direct correlation was identified with the other measured ISPs. Receiver operating characteristic (ROC) analysis showed that the z-score of the composite of ERFE+FRT has a full diagnostic ability for β-TM. In conclusion, our finding indicated the correlation between different ISPs, FRT as the leading predictor of iron overload and tow main iron regulatory hormones.

Screening For Thalassemia Carriers In Populations With High Rate Of Iron Deficiency: Revisiting The Applicability Of Mentzer Index and The Effect Of Iron Deficiency On HbA2 Level

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 1023-1023
Author(s):  
Ali Amid ◽  
Bahram Haghi Ashtiani ◽  
Mohammad Taghi Haghi Ashtiani
Keyword(s):  
Genetic Testing ◽  
Iron Deficiency ◽  
Conflicts Of Interest ◽  
Iron Status ◽  
Pediatric Population ◽  
Ferritin Level ◽  
High Rate ◽  
Beta Thalassemia ◽  
Relative Reduction ◽  
Number Of Patients

Abstract Background Iron deficiency (ID) and beta thalassemia carrier state (Tm) are the two most common causes of microcytosis in pediatric population. Differentiating between these conditions has therapeutic significance as well as important implications in thalassemia carrier screening. Since Menzter first reported his observation on the applicability of “Mentzer Index” in differentiating Tm from IDA with a reasonable reliability, several other formulas have been developed and tested. However, one major concern, that is the high probability of the concurrence of the two conditions in countries where both ID and Tm are common, limits their use. It is not possible to separate ID from Tm with these formulas when considerable portion of patients have both conditions. This study was done to investigate the function of Mentzer Index in patients with concurrent ID and Tm. In addition we investigated the effect of ID on HbA2 level in Tm subjects and ID only patients as several previous studies have reported conflicting results on the effect of ID on the HbA2 levels. Methods We retrospectively analyzed the CBC, iron indices and HPLC results of pediatric patients (1-18 years) who were referred to a tertiary laboratory in Iran for over a 10 year period and had a diagnosis of ID only, Tm only, or ID+Tm. Only those who had complete CBC, RDW, ferritin and HPLC were included. Diagnosis of Tm was based on HbA2 >3.5%. ID only patients were diagnosed based on HbA2 <3.5%, ferritin <20 μg/dL and resolution of microcytosis following iron supplementation. Patients with ID+Tm were diagnosed if ferritin was < 20 μg/dL and HbA2 was > 3.5%. We defined modified Mentzer Index (mMI) as (MCV/RBC)-13. 45 subjects (17 with IDA) had confirmed diagnosis of Tm with genetic testing, all with HbA2> 3.5. Results 562 Patients were qualified (ID only: 333, Tm only: 131, ID+Tm: 98 patients, 286 females). mMI was < 0 in 127/131 (96%) of Tm only, and > 0 in 243/333 (72%) in ID only patients. Interestingly, however, in patients with ID+Tm, mMI was < 0 in 94/98 (95%). Further analysis (Spearman correlation) indicated that mMI was significantly correlated (inversely) with HbA2 level in Tm patients with or without ID [P<0.001], and in ID only patients [P=0.017]. Ferritin level was not correlated with mMI in Tm patients with or without ID [P=0.581], or in ID only patients [P=0.718]. In addition, HbA2 was correlated with ferritin in ID only patients [p=0.007], but not in Tm patients with or without ID [p=0.173], including in those Tm subjects with genetic testing. Conclusions It is well recognized that individuals with Tm have higher RBC counts compared to ID patients. The underlying molecular pathophysiology of this, however, is not well defined. Our study demonstrates that the number of RBCs in relation to patient’s MCV directly correlates with HbA2 (inverse relation to mMI). Also, the presence or the degree of iron deficiency does not affect mMI, so the variation in RBC numbers in relation to the degree of microcytosis is related to HbA2 level only and not ID. It appears that mMI (or Mentzer Index) separates Tm from non-Tm individuals rather than Tm from ID patients. Further studies are required to investigate the molecular basis of phenotypic variations of erythropoiesis in relation to different hemoglobins variants like HbA2. Mentzer index can be used, with reasonably high sensitivity, to initiate screening for Tm regardless of iron status, in low resource settings. Furthermore, in our population, while ferritin level was associated with decreased HbA2 in ID only patients, this effect was not observed in individuals with Tm. We have demonstrated this in a large number of patients with ID only, Tm only, and ID+Tm, in contrast to previous studies which were done on either limited numbers or on subsets of patients. In healthy individuals, there is a relative excess of α chains compared to β chains. In the presences of ID, more reduction of α chains compared to β chains is observed which results in increased competition between β and δ chains for limited available α chains and subsequent reduction of HbA2 levels. However, in Tm patients where β chain production is also reduced, relative reduction of α chain due to ID will not be severe enough to reduce the formation of HbA2 in favor of HbA. It appears that correction of ID is not required to diagnose thalassemia carriers by HPLC or Hb electrophoresis. Of note we did not include Tm individuals with borderline/normal HbA2 (<3.5%) in this study. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Determination of Lipid Profile in Preschool Children and Precollege Students with Beta-thalassemia Minor and Control Group

2016 ◽  
Vol 13 (2) ◽  
pp. 1259-1264 ◽  
Author(s):  
Mahdi Shahriari ◽  
Reza Sahraei ◽  
Abdolreza Sotoodeh Jahromi ◽  
Abdolreza Afrasiabi
Keyword(s):  
Preschool Children ◽  
Lipid Profile ◽  
Beta Thalassemia ◽  
Control Group ◽  
Thalassemia Minor ◽  
And Control

Evaluation of Iron Status by Serum Ferritin Level in Iranian Carriers of Beta Thalassemia Minor

2008 ◽  
Vol 78 (45) ◽  
pp. 204-207 ◽  
Author(s):  
Hamid Hoorfar ◽  
Shohreh Sadrarhami ◽  
Ammar Hassanzadeh Keshteli ◽  
Samaneh Khanpour Ardestani ◽  
Manijeh Ataei ◽  
...  
Keyword(s):  
Iron Overload ◽  
Serum Ferritin ◽  
Iron Status ◽  
Ferritin Level ◽  
Beta Thalassemia ◽  
Control Group ◽  
Similar Data ◽  
Thalassemia Minor ◽  
The Mean ◽  
Harmful Effects

Background: Conflicting data exists on iron metabolism in adults with beta thalassemia minor (BTM). The purpose of this study was to evaluate the serum ferritin (SF) levels in Iranian adults with BTM in order to determine the iron status in these subjects. Methods: Eighty four (41 males, 43 females) Iranian adults with BTM and 102 (55 males, 47 females) healthy subjects as a control group were enrolled in the study. SF level was measured by immunoradiometric assay (IRMA). Results: The mean SF concentration in the BTM group was 101.84 ± 8.5 μg/L, which was higher than the mean SF in non-BTM subjects (67.98 ± 5.4 μg/L, p = 0.001). Comparing SF concentrations between BTM males and males in the control group showed that the SF level was significantly higher in BTM males (150.57 ± 75.13 μg/L vs. 96.66 ± 56.79 μg/L, p < 0.001). Similar data was found for females (55.38 ± 47.94 μg/L in the BTM group vs. 34.42 ± 25.72 μg/L in the non-BTM group, p = 0.01). Conclusion: This study showed that BTM may play a role in improving iron status in females with BTM. However in males, BTM can lead to iron overload. Therefore, we suggest determining the levels of SF in subjects with BTM, especially in males, to avoid harmful effects of iron overload in early stages of the disorder.

Heme Oxygenase 1 Plays a Role In The Pathophysiology Of β-Thalassemia

Blood ◽  
2013 ◽  
Vol 122 (21) ◽  
pp. 3449-3449 ◽  
Author(s):  
Daniel Garcia Santos ◽  
Marc Mikhael ◽  
Stefano Rivella ◽  
Monika Horvathova ◽  
Prem Ponka
Keyword(s):  
Heme Oxygenase ◽  
Conflicts Of Interest ◽  
Erythroid Differentiation ◽  
Thalassemia Major ◽  
Severe Form ◽  
Cellular Damage ◽  
Heme Oxygenase 1 ◽  
Globin Chains ◽  
Thalassemia Minor ◽  
Free Heme

Abstract Thalassemias are a heterogeneous group of red blood cell disorders ranging from a clinically severe phenotype requiring life-saving transfusions (thalassemia major) to a relatively moderate symptomatic disorder, sometimes requiring transfusions (thalassemia intermedia). Thalassemia minor, the least severe form of the disorder, is characterized by minimal to mild symptoms. While thalassemia minor and intermedia are vastly more prevalent than thalassemia major, the latter is often fatal when not treated. Though considered a major cause of morbidity and mortality worldwide, there is still no universally available cure for this severe form of thalassemia. A reason for this is at least in part due to the lack of full understanding of pathophsyiology of thalassemia. The underlying cause of pathology in thalassemia is the premature apoptotic destruction of erythroblasts causing ineffective erythropoeisis. Normally, the assembly of adult hemoglobin (consisting of a tetramer of two α- and two β-globin chains) features a very tight coordination of α- and β-globin chain synthesis. However, in β-thalassemia, β-globin synthesis is decelerated causing α-globin accumulation; while in α-thalassemia the opposite scenario occurs. Unpaired globin chains that accumulate in thalassemic erythroblasts are bound to heme. In addition, in β-thalassemia an erythroid specific protease destroys excess α-globin chains, likely leading to the generation of a pool of “free” heme in erythroblasts. “Free” heme is toxic, but this toxicity will likely be augmented, if heme oxygenase 1 (HO-1) can release iron from heme. To date, virtually no information about the expression of HO-1 in erythroblasts has been produced; however, we have recently provided unequivocal evidence that this enzyme is present in several model erythroid cells1. Based on this novel and important finding, we hypothesize that in β-thalassemic erythroblasts HO-1 mediated release of iron from heme is the major culprit responsible for cellular damage. To test this hypothesis we exploited the mouse model of β-thalassemia, th3/+. Thus far, our data indicates that HO-1 expression is increased in liver, spleen and kidney of β-thalassemic mice compared to wild type mice. Importantly, we observed that Epo-mediated erythroid differentiation of fetal liver (FL) cells isolated from β-thalassemic fetuses, display increased levels of HO-1 as well as decreased phosphorylated eiF2-α. These results indicate that β-thalassemic erythroblasts have inappropriately high levels of unbound heme that is continuously degraded by HO-1. Further research is needed to determine whether HO-1 liberated iron is responsible for the damage of β-thalassemic erythroblasts. 1Garcia Santos D, Schranzhofer M, Bogo Chies JA, Ponka P. Heme Oxygenase 1 plays an unexpected role during erythroid differentiation. Blood (ASH Annual Meeting Abstracts) 118: 344, 2011. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Cytokine Dependent Hematopoietic Cell Linker (CLNK) is Highly Elevated in Blood Transfusion Dependent Beta-Thalassemia Major Patients

2019 ◽  
Author(s):  
Hussein Kadhem Al-Hakeim ◽  
Hawraa Hussein Al-Mayali ◽  
Michael Maes
Keyword(s):  
Iron Status ◽  
Globin Gene ◽  
Adaptor Protein ◽  
Thalassemia Major ◽  
Severe Form ◽  
Hematopoietic Cell ◽  
Beta Thalassemia ◽  
Beta Globin ◽  
Beta Thalassemia Major ◽  
Globin Chains

Beta-thalassemia major (&beta;-TM) is a severe form of thalassemia caused by mutations in the &beta;-globin gene, resulting in partial or complete deficiency of &beta;-globin chains. This deficiency results in oxidative stress, dyserythropoiesis, and chronic anemia. Cytokine dependent hematopoietic cell linker (CLNK) belongs to the adaptor protein family and has the capacity to interact with multiple signaling proteins thereby modulating signal transduction. The aim of the present study was to examine CLNK in sera of &beta;-TM patients and examine its association with iron overload biomarkers. Sixty &beta;-TM patients, aged 3&ndash;12 years old and undergoing blood transfusions, and 30 healthy control children were recruited and CLNK, ferritin and iron status parameters were measured. The results showed a significant increase (p &lt; 0.001) in serum CLNK levels in &beta;-TM patients as compared with normal controls. The increased levels of CLNK were significantly associated with increased ferritin levels. Increased CLNK levels in &beta;-TM may be explained by reciprocal effects between immune signaling and immature erythrocytes, which, release soluble receptors and signaling molecules, including CLNK, in the blood.

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