Sample records for beta-thalassemia

  1. Beta Thalassemia (United States)

    Beta thalassemia is found in people of Mediterranean, Middle Eastern, African, South Asian (Indian, Pakistani, etc.), Southeast Asian and Chinese descent. 1 Beta Thalassemia ßß Normal beta globin genes found on chromosomes ...

  2. Genetics Home Reference: beta thalassemia (United States)

    ... Understand Genetics Home Health Conditions beta thalassemia beta thalassemia Enable Javascript to view the expand/collapse boxes. Download PDF Open All Close All Description Beta thalassemia is a blood disorder that reduces the production ...

  3. Beta Thalassemia (For Parents) (United States)

    ... had their spleens removed. Slower growth rates. The anemia resulting from beta thalassemia can cause children to grow more slowly and also can lead ... boost production of new red blood cells. Some children with moderate anemia may require an occasional blood transfusion , particularly after ...

  4. Beta-thalassemia

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    Origa Raffaella


    Full Text Available Abstract Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands, dilated myocardiopathy, liver fibrosis and cirrhosis. Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes, gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely

  5. Beta-thalassemia. (United States)

    Galanello, Renzo; Origa, Raffaella


    Beta-thalassemias are a group of hereditary blood disorders characterized by anomalies in the synthesis of the beta chains of hemoglobin resulting in variable phenotypes ranging from severe anemia to clinically asymptomatic individuals. The total annual incidence of symptomatic individuals is estimated at 1 in 100,000 throughout the world and 1 in 10,000 people in the European Union. Three main forms have been described: thalassemia major, thalassemia intermedia and thalassemia minor. Individuals with thalassemia major usually present within the first two years of life with severe anemia, requiring regular red blood cell (RBC) transfusions. Findings in untreated or poorly transfused individuals with thalassemia major, as seen in some developing countries, are growth retardation, pallor, jaundice, poor musculature, hepatosplenomegaly, leg ulcers, development of masses from extramedullary hematopoiesis, and skeletal changes that result from expansion of the bone marrow. Regular transfusion therapy leads to iron overload-related complications including endocrine complication (growth retardation, failure of sexual maturation, diabetes mellitus, and insufficiency of the parathyroid, thyroid, pituitary, and less commonly, adrenal glands), dilated myocardiopathy, liver fibrosis and cirrhosis). Patients with thalassemia intermedia present later in life with moderate anemia and do not require regular transfusions. Main clinical features in these patients are hypertrophy of erythroid marrow with medullary and extramedullary hematopoiesis and its complications (osteoporosis, masses of erythropoietic tissue that primarily affect the spleen, liver, lymph nodes, chest and spine, and bone deformities and typical facial changes), gallstones, painful leg ulcers and increased predisposition to thrombosis. Thalassemia minor is clinically asymptomatic but some subjects may have moderate anemia. Beta-thalassemias are caused by point mutations or, more rarely, deletions in the beta

  6. Factors Influencing Beta-Thalassemia Awareness in Western India


    Ashwin P Patel; Prakash H Parmar; Rupesh B Patel; Nikhil M Trivedi; Nileshkumar A Bhartiya


    "Context: Beta-thalassemia is highly prevalent in western India. Our organization runs a screening and prevention program to create awareness and reduce the incidence of homozygous beta-thalassemia cases. Aims: The study was designed to evaluate factors influencing awareness about Beta-thalassemia. Methodology: This cross sectional survey was conducted at six colleges, two medical clinics, and a thalassemia transfusion centre. It involved 398 adults ( and #8805;18 years).The survey form...

  7. Intracranial Extramedullary Hematopoiesis in Beta-Thalassemia

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    Karki, Bivek; Xu, Yi Kai; Wu, Yuan Kui [Nan fang Hospital, Southern Medical University, Guangzhou (China); Tamrakar, Karuna [Zhujiang Hospital, Southern Medical University, Guangzhou (China)


    Extramedullary hematopoiesis (EMH) represents tumor-like proliferation of hemopoietic tissue which complicates chronic hemoglobinopathy. Intracranial EMH is an extremely rare occurrence. Magnetic resonance imaging (MRI) offers a precise diagnosis. It is essential to distinguish EMH from other extradural central nervous system tumors, because treatment and prognosis are totally different. Herein, we report the imaging findings of beta-thalassemia in a 13-year-old boy complaining of weakness of left side of the body and gait disturbance; CT and MRI revealed an extradural mass in the right temporoparietal region.

  8. mRNA expression of iron regulatory genes in beta-thalassemia intermedia and beta-thalassemia major mouse models. (United States)

    Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rachmilewitz, Eliezer; Breda, Laura; Rivella, Stefano; Rechavi, Gideon


    beta-Thalassemia is an inherited anemia in which synthesis of the hemoglobin beta-chain is decreased. The excess unmatched alpha-globin chains accumulate in the growing erythroid precursors, causing their premature death (ineffective erythropoiesis). Clinical features of beta-thalassemia include variably severe anemia and iron accumulation due to increased intestinal iron absorption. The most anemic patients require regular blood transfusions, which exacerbate their iron overload and result in damage to vital organs. The hepatic peptide hepcidin, a key regulator of iron metabolism in mammals, was recently found to be low in the urine of beta-thalassemia patients, compared with healthy controls, despite their iron overload. In our work, we measured by RQ-PCR the liver mRNA expression of hepcidin and other iron regulatory genes in beta-thalassemia major mouse model (C57Bl/6 Hbb(th3/th3)), and compared it with beta-thalassemia intermedia mouse model (C57Bl/6 Hbb(th3/+)) and control mice. We found decreased expression of hepcidin and TfR2 and increased expression of TfR1 and NGAL in the beta-thalassemia mouse models, compared with the control mice. Significant down-regulation of hepcidin expression in beta-thalassemia major, despite iron overload, might explain the increased iron absorption typically observed in thalassemia.

  9. Management of beta-thalassemia-associated osteoporosis. (United States)

    Giusti, Andrea; Pinto, Valeria; Forni, Gian Luca; Pilotto, Alberto


    Beta-Thalassemia-associated osteoporosis is a multifactorial and complex condition. Different acquired and genetic factors are involved in its pathogenesis. These factors produce an imbalance in bone remodeling by inhibiting osteoblast activity and increasing osteoclast function, leading to bone loss and increased fracture risk. The management of patients presenting with thalassemia-associated osteoporosis should consist of the implementation of general measures and the prescription of a specific pharmacological agent, with the aim of reducing fracture risk and preventing disability and deterioration of quality of life. General measures include control of anemia, adequate chelation therapy, healthy nutrition and lifestyle, regular exercise, adequate management of comorbid conditions, hormone replacement therapy in patients with hypogonadism, and vitamin D supplementation/therapy. Among the pharmacological agents currently available for the management of osteoporosis in postmenopausal women and men, bisphosphonates have been shown to improve bone mineral density, to reduce bone turnover, and to decrease bone/back pain in patients with thalassemia-associated osteoporosis, with a good profile of safety and tolerability. On the other hand, there are limited experiences with other pharmacological agents (e.g., denosumab or teriparatide). The complexity of this condition presents diagnostic and therapeutic challenges and underscores the importance of a comprehensive and multidisciplinary approach.

  10. Prevalence of hepatosplenomegaly in beta thalassemia minor subjects in Iran

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    Karimi, Mehran [Hemostasis and Thrombosis Unit, Hematology Research Center, school of Medicine, Shiraz University of medical sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Bagheri, Mohammad Hadi [Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Tahmtan, Mehdi [Hemostasis and Thrombosis Unit, Hematology Research Center, school of Medicine, Shiraz University of medical sciences, Shiraz (Iran, Islamic Republic of); Shakibafard, Alireza [Department of Radiology, School of Medicine, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of); Rashid, Murtaza [Hemostasis and Thrombosis Unit, Hematology Research Center, school of Medicine, Shiraz University of medical sciences, Shiraz (Iran, Islamic Republic of)


    Introduction: Thalassemia is the most common hereditary blood disorder in the world. Iran is located on the thalassemic belt and there is a high prevalence of the hepatosplenomegaly in beta thalassemia minor patients which is reported to be very variable. The goal of this research was to study the frequency of these signs in the cases with beta thalassemia minor patients in Iran. Materials and methods: Two hundred and fifty-nine cases that referred to center for pre-marriage tests were divided into two groups according to their MCV, MCH, and HbA2 (beta thalassemia minor cases and control groups). Liver and spleen sizes were determined by ultrasonographic method and the two groups were compared with each other. Results: Average spleen volumes in case and control groups were 163.48 {+-} 133.97 and 126.29 {+-} 53.98 mm{sup 3}, respectively. Average spleen lengths in case and control groups were 10.71 {+-} 1.52 and 10.60 {+-} 5.4 cm, respectively. Conclusion: In the regions with high frequency of beta thalassemia, in case of finding large spleen size in the ultrasonography, a probable harmless differential diagnosis will be beta thalassemia minor that is not indicative of any serious disease. Volumetric measurement of spleen is more reliable for detection of splenomegaly in these patients.

  11. Hepcidin and Hfe in iron overload in beta-thalassemia. (United States)

    Gardenghi, Sara; Ramos, Pedro; Follenzi, Antonia; Rao, Niva; Rachmilewitz, Eliezer A; Giardina, Patricia J; Grady, Robert W; Rivella, Stefano


    Hepcidin (HAMP) negatively regulates iron absorption, degrading the iron exporter ferroportin at the level of enterocytes and macrophages. We showed that mice with beta-thalassemia intermedia (th3/+) have increased anemia and iron overload. However, their hepcidin expression is relatively low compared to their iron burden. We also showed that the iron metabolism gene Hfe is down-regulated in concert with hepcidin in th3/+ mice. These observations suggest that low hepcidin levels are responsible for abnormal iron absorption in thalassemic mice and that down-regulation of Hfe might be involved in the pathway that controls hepcidin synthesis in beta-thalassemia. Therefore, these studies suggest that increasing hepcidin and/or Hfe expression could be a strategy to reduces iron overload in these animals. The goal of this paper is to review recent findings that correlate hepcidin, Hfe, and iron metabolism in beta-thalassemia and to discuss potential novel therapeutic approaches based on these recent discoveries.

  12. Oxidative stress and antioxidant status in beta-thalassemia heterozygotes

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    Luciana de Souza Ondei


    Full Text Available Background: Several studies have evaluated the oxidant and antioxidant status of thalassemia patients but most focused mainly on the severe and intermediate states of the disease. Moreover, the oxidative status has not been evaluated for the different beta-thalassemia mutations. Objective: To evaluate lipid peroxidation and Trolox equivalent antioxidant capacity in relation to serum iron and ferritin in beta thalassemia resulting from two different mutations (CD39 and IVS-I-110 compared to individuals without beta-thalassemia. Methods: One hundred and thirty subjects were studied, including 49 who were heterozygous for beta-thalassemia and 81 controls. Blood samples were subjected to screening tests for hemoglobin. Allele-specific polymerase chain reaction was used to confirm mutations for beta-thalassemia, an analysis of thiobarbituric acid reactive species was used to determine lipid peroxidation, and Trolox equivalent antioxidant capacity evaluations were performed. The heterozygous beta-thalassemia group was also evaluated for serum iron and ferritin status. Results: Thiobarbituric acid reactive species (486.24 ± 119.64 ng/mL and Trolox equivalent antioxidant capacity values (2.23 ± 0.11 mM/L were higher in beta-thalassemia heterozygotes compared to controls (260.86 ± 92.40 ng/mL and 2.12 ± 0.10 mM/L, respectively; p-value < 0.01. Increased thiobarbituric acid reactive species values were observed in subjects with the CD39 mutation compared with those with the IVS-I-110 mutation (529.94 ± 115.60 ng/mL and 453.39 ± 121.10 ng/mL, respectively; p-value = 0.04. However, average Trolox equivalent antioxidant capacity values were similar for both mutations (2.20 ± 0.08 mM/L and 2.23 ± 0.12 mM/L, respectively; p-value = 0.39. There was no influence of serum iron and ferritin levels on thiobarbituric acid reactive species and Trolox equivalent antioxidant capacity values. Conclusion: This study shows an increase of oxidative stress and


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    Full Text Available Introduction: Due to the prevalence of beta thalassemia and iron deficiency anemia in Irana need for an accurate, quick, inexpensive and simple method for differential diagnosis between these two disorders is felt. In this study the value of zpp measurement as a tool to distinguish iron deficiency from heterozygous beta thalassemia in microcrystal patients was evaluated. Methods: In this study on 140 persons with microcytosis, the hemoglobin electrophoresis, serum iron, TIBC and serum ferritin and protoporphyrine relating to zinc (ZPP were measured. Results: ZPP had been increased in all iron deficient patients and in 53 percent of Heterozygote beta thalassemia patients. Using combination of MCV and ZPP in iron deficient anemic patients and heterozygote beta thalassemia show the 99 percent accuaracy in differentiation of these two disorders. Discussion: According to the results, this method has better accuracy than red blood cells formulation in the screening programs for beta thalassemia and iron defficiency anemia.

  14. X-ray scattering signatures of {beta}-thalassemia

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    Desouky, Omar S. [Radiation Physics Department, National Center for Radiation Research and Technology (NCRRT) (Egypt); Elshemey, Wael M. [Biophysics Department, Faculty of Science, Cairo University (Egypt)], E-mail:; Selim, Nabila S. [Radiation Physics Department, National Center for Radiation Research and Technology (NCRRT) (Egypt)


    X-ray scattering from lyophilized proteins or protein-rich samples is characterized by the presence of two characteristic broad peaks at scattering angles equivalent to momentum transfer values of 0.27 and 0.6 nm{sup -1}, respectively. These peaks arise from the interference of coherently scattered photons. Once the conformation of a protein is changed, these two peaks reflect such change with considerable sensitivity. The present work examines the possibility of characterizing the most common cause of hemolytic anaemia in Egypt and many Mediterranean countries; {beta}-thalassemia, from its X-ray scattering profile. This disease emerges from a genetic defect causing reduced rate in the synthesis of one of the globin chains that make up hemoglobin. As a result, structurally abnormal hemoglobin molecules are formed. In order to detect such molecular disorder, hemoglobin samples of {beta}-thalassemia patients are collected, lyophilized and measured using a conventional X-ray diffractometer. Results show significant differences in the X-ray scattering profiles of most of the diseased samples compared to control. The shape of the first scattering peak at 0.27 nm{sup -1}, in addition to the relative intensity of the first to the second scattering peaks, provides the most reliable signs of abnormality in diseased samples. The results are interpreted and confirmed with the aid of Fourier Transform Infrared (FTIR) spectroscopy of normal and thalassemia samples.

  15. Molecular basis of asymptomatic beta-thalassemia major in an African American individual. (United States)

    Ballas, S K; Cai, S P; Gabuzda, T; Chehab, F F


    The beta-thalassemia syndromes are a heterogeneous group of genetic disorders characterized by reduced or absent expression of the beta-globin gene. To date, over 300 beta-thalassemia alleles have been characterized in or around the beta-globin region. Thalassemia major is severe anemia necessitating chronic blood transfusions, splenectomy, iron chelation therapy, and bone marrow transplantation. Usually thalassemia major results from homozygosity or compound heterozygosity for severe betaO- and/or beta+-thalassemia mutations. Thalassemia intermedia is a clinical diagnosis that describes a symptomatic but less severe condition than beta-thalassemia major. beta-thalassemia intermedia may arise from several different combinations of alpha- and/or beta-thalassemia mutations. Heterozygous beta-thalassemia is typically characterized by a mild microcytic hypochromic anemia without any significant clinical implications. In this report, we describe a 63-year-old Africian American woman with asymptomatic homozygous beta-thalassemia, who seems to carry 2 copies of the -29 mutation in the promoter region of the beta-globin gene. Her elevated hemoglobin F level of 83% was associated with heterozygosity for the Xmn I polymorphism upstream of the Ggamma-globin gene. Southern blot analysis at the alpha-globin locus did not show any deletion that would account for the mildness of her phenotype. Therefore, homozygosity for the -29 mutation along with the Xmn I polymorphism appears to confer an extremely mild beta-thalassemia phenotype. This observation has important implications in the prenatal diagnosis and genetic counseling of families segregating this type of genetic defect.

  16. Progress toward the genetic treatment of the beta-thalassemias. (United States)

    Sadelain, Michel; Lisowski, Leszek; Samakoglu, Selda; Rivella, Stefano; May, Chad; Riviere, Isabelle


    The beta-thalassemias are congenital anemias that are caused by mutations that reduce or abolish expression of the beta-globin gene. They can be cured by allogeneic hematopoietic stem cell (HSC) transplantation, but this therapeutic option is not available to most patients. The transfer of a regulated beta-globin gene in autologous HSCs is a highly attractive alternative treatment. This strategy, which is simple in principle, raises major challenges in terms of controlling expression of the globin transgene, which ideally should be erythroid specific, differentiation- and stage-restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, May et al. demonstrated in 2000 that an optimized combination of proximal and distal transcriptional control elements permits lineage-specific and elevated beta-globin expression, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Several groups have by now replicated and extended these findings to various mouse models of severe hemoglobinopathies, thus fueling enthusiasm for a potential treatment of beta-thalassemia based on globin gene transfer. Current investigation focuses on safety issues and the need for improved vector production methodologies. The safe implementation of stem cell-based gene therapy requires the prevention of the formation of replication-competent viral genomes and minimization of the risk of insertional oncogenesis. Importantly, globin vectors, in which transcriptional activity is highly restricted, have a lesser risk of activating oncogenes in hematopoietic progenitors than non-tissue-specific vectors, by virtue of their late-stage erythroid specificity. As such, they provide a general paradigm for improving vector safety in stem cell-based gene therapy.

  17. Magnetic measurements on human erythrocytes: Normal, beta thalassemia major, and sickle (United States)

    Sakhnini, Lama


    In this article magnetic measurements were made on human erythrocytes at different hemoglobin states (normal and reduced hemoglobin). Different blood samples: normal, beta thalassemia major, and sickle were studied. Beta thalassemia major and sickle samples were taken from patients receiving lifelong blood transfusion treatment. All samples examined exhibited diamagnetic behavior. Beta thalassemia major and sickle samples showed higher diamagnetic susceptibilities than that for the normal, which was attributed to the increase of membrane to hemoglobin volume ratio of the abnormal cells. Magnetic measurements showed that the erythrocytes in the reduced state showed less diamagnetic response in comparison with erythrocytes in the normal state. Analysis of the paramagnetic component of magnetization curves gave an effective magnetic moment of μeff=7.6 μB per reduced hemoglobin molecule. The same procedure was applied to sickle and beta thalassemia major samples and values for μeff were found to be comparable to that of the normal erythrocytes.

  18. Pyogenic liver abscess in beta-thalassemia major--report of two cases. (United States)

    Hwang, C F; Lee, C Y; Lee, P I; Chen, J M; Lli, K H; Lin, D T; Chang, M H


    Pyogenic liver abscess, which may lead to devastating consequences, is an uncommon medical problem in pediatrics and has generally been reported in compromised hosts. This article describes two patients with beta-thalassemia major and hemochromatosis complicated by Klebsiella pneumoniae liver abscess. One of the patients had severe complications, including subphrenic abscess, pleural effusion and meningitis. To present knowledge, the occurrence of K. pneumoniae liver abscess in patients with beta-thalassemia major has never before been reported in the literature.


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    Awaz Ahmed Kamal


    Full Text Available Background: HbA2 plays a key role in screening programs for beta thalassemia because a small increase in this fraction is the most important marker of beta thalassemia heterozygous carriers. The potential impact of coincident iron deficiency on HbA2 based identification of beta thalassemia minor is worrisome issue for screening laboratories, this is especially true for resource-constrained settings where iron deficiency is wide spread and molecular confirmatory tests for borderline HbA2 values may be unavailable. Objective: the aim of this study is to evaluate the effect of iron deficiency on HbA2 level in order to improve the detection of beta thalassemia trait with or without iron deficiency in our population. Materials and Method: In this study 145 individuals were enrolled including normal controls (50, beta thalassemia minor (50 and coincident beta thalassemia with iron deficiency cases (45. Complete blood count, serum iron, total iron binding capacity and HbA2 with HbF estimation were done for every individual. Result: The mean HbA2 level was (2.4± 0.4 in control, (5.2 ± 0.9 in beta thalassemia minor and 5.1± 0.9 in coincident iron deficiency with beta thalassemia minors. All hematological parameters were significantly lower in beta thalassemia minor and coincident iron deficiency with beta thalassemia minor in comparison to the control group .Mean HbA2 level did not show a significant difference in thalassemia minor (5.2±0.9 when compared with the mean HbA2 levels in coincidentiron deficiency with beta thalassemia minor. Conclusion: The presence of iron deficiency did not preclude the detection of beta thalassemia minor in our population

  20. Could Heterozygous Beta Thalassemia Provide Protection Against Multiple Sclerosis? (United States)

    Cikrikcioglu, Mehmet Ali; Ozcan, Muhammed Emin; Halac, Gulistan; Gultepe, Ilhami; Celik, Kenan; Sekin, Yahya; Eser, Elif Ece; Burhan, Sebnem; Cetin, Guven; Uysal, Omer


    Background Heterozygous beta thalassemia (HBT) has been proposed to increase the risk of developing autoimmune disease. Our aim in this study was to examine the prevalence of HBT among multiple sclerosis (MS) patients. Material/Methods HBT frequency was investigated in our MS group (243 patients with MS). Hemoglobin electrophoresis (HE) was carried out if MS patients had a mean corpuscular volume of (MCV) <80 fL and a mean corpuscular hemoglobin level of (MCH) <27 pg/L according to a complete blood count (CBC). If MCV was lower than 80 fL, MCH was lower than 27 pg/L, and Hemoglobin A2 equal to or higher than 3.5%, a diagnosis of HBT was established. The frequency of patients with HBT in our MS patient group was statistically compared with the prevalence of HBT in the city of Istanbul, where our MS patients lived. Results The HBT prevalence was 0.823% (2 patients) in the MS patient group. The prevalence of HBT in Istanbul has been reported to be 4.5%. According to the z-test, the HBT prevalence in our MS patient group was significantly lower than that in Istanbul (Z=6.3611, two-sided p value <0.0001, 95% confidence interval of prevalence of HBT in our MS patient group: 0.000998–0.029413). Conclusions Contrary to our hypothesis at the outset of study, the reduced HBT prevalence in the MS group compared to HBT frequency in the city of Istanbul might indicate that HBT is protective against MS. PMID:27941710

  1. Spinal cord compression in {beta}-thalassemia: follow-up after radiotherapy

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    Fonseca, Silvana Fahel da; Figueiredo, Maria Stella; Cancado, Rodolfo Delfini; Nakadakare, Fernando; Segreto, Roberto; Kerbauy, Jose [Universidade Federal de Sao Paulo (UNIFESP), SP (Brazil). Escola Paulista de Medicina


    Spinal cord compression due to extramedullary hematopoiesis is a well-described bu rare syndrome encountered in several hematologic disorders, including {beta}-thalassemia. We report a case of a patient with intermediate {beta}-thalassemia and crural paraparesis due to spinal cord compression by a paravertebral extramedullary mass. She was successfully treated with low-dose radiotherapy and transfusions. After splenectomy, she was regularly followed up for over four years without transfusion or recurrence of spinal cord compression. Extramedullary hematopoiesis should be investigated in patients with hematologic disorders and spinal cord symptoms. The rapid recognition and treatment with radiotherapy can dramatically alleviate symptoms. (author)

  2. Human parvovirus B19 in patients with beta thalassemia major from Tehran, Iran (United States)

    Arabzadeh, Seyed Ali Mohammad; Alizadeh, Farideh; Tavakoli, Ahmad; Mollaei, Hamidreza; Bokharaei-Salim, Farah; Karimi, Gharib; Farahmand, Mohammad; Mortazavi, Helya Sadat


    Background Due to the tropism of human parvovirus B19 to erythroid progenitor cells, infection in patients with an underlying hemolytic disorder such as beta-thalassemia major leads to suppression of erythrocyte formation, referred to as transient aplasia crisis (TAC), which may be life-threatening. We investigated the prevalence of parvovirus B19 among patients with beta thalassemia major attending the Zafar Adult Thalassemia Clinic in Tehran, Iran. Methods This cross-sectional study was performed to determine the presence of parvovirus B19 DNA in blood samples and parvovirus B19 genotypes in plasma samples of patients with thalassemia major. The population consisted of 150 patients with beta-thalassemia major who attended the Zafar clinic in Tehran. Specimens were studied using a real-time polymerase chain reaction assay. Results The prevalence of parvovirus B19 in our study population was 4%. Of 150 patients with thalassemia, six (4%) were positive for B19 DNA. There was no significant correlation between blood transfusion frequency and B19 DNA positivity. Finally, phylogenetic analysis of human parvovirus B19 revealed genotype I in these six patients. Conclusion In this study, acute B19 infections were detected in patients with beta thalassemia major. Screening of such high-risk groups can considerably reduce the incidence and prevalence of B19 infection; thus, screening is required for epidemiologic surveillance and disease-prevention measures.

  3. Renal tubular dysfunction with nephrocalcinosis in a patient with beta thalassemia minor

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    Prabahar Murugesan


    Full Text Available Thalassemia is a hereditary anemia resulting from defect in hemoglobin production. Beta thalassemia is due to impaired production of beta globin chains, leading to a relative excess of alpha globin chains. The term beta thalassemia minor is used to describe heterozygotes, who carry one normal beta globin allele and one beta thalassemic allele. The vast majority of these patients are asymptomatic. However, a variety of renal tubular abnormalities including hypercalciuria, hypo-magnesemia with renal magnesium wasting, decreased tubular absorption of phosphorus, hypo-uricemia with renal uric acid wasting, renal glycosuria and tubular proteinuria have been described even in patients with beta thalassemia minor. We here in report a 24-year old female patient who was found to have thalassemia minor and nephrocalcinosis with evidence of renal tubular dysfunction. Investigations revealed normal renal function, hypercalciuria, reduced tubular reabsorption of phos-phorus, hypomagnesemia and renal magnesium wasting. Screening for aminoaciduria was found to be negative. An acid loading test revealed normal urinary acidification. Ultrasonogram of the abdomen revealed nephrocalcinosis and splenomegaly. Detailed work up for anemia showed normal white cell and platelet count while peripheral smear showed microcytic hypochromic anemia with few target cells. Hemoglobin electrophoresis revealed hemoglobin A of 92%, hemoglobin A2 of 6.2% and hemo-globin F of 1.8% consistent with beta thalassemia minor. Her parental screening was normal. A diag-nosis of beta thalassemia minor with renal tubular dysfunction was made and the patient was started on thiazide diuretics to reduce hypercalciuria and advised regular follow-up.

  4. Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia1, or beta-thalassemia and in compound heterozygotes for HbE/ beta-thalassemia


    M.B. Zimmermann; Fucharoen, S; Winichagoon, P.; Sirankapracha, P.; Zeder, C.; Gowachirapant, S.; Judprasong, K.; Tanno, T.; Miller, J. L.; Hurrell, R. F.


    BACKGROUND: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons. OBJECTIVE: We aimed to determine whether iron absorption or utilization (or both) in women heterozygous for beta-thalassemia, alpha-thalassemia 1, or hemoglobin E (HbE) differed from that in control subjects and compound HbE/beta-thalassemia heterozygotes. DESIGN: In Thai women (n = 103), re...

  5. Molecular analysis of beta-globin gene mutations among Thai beta-thalassemia children: results from a single center study

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    Boonyawat B


    Full Text Available Boonchai Boonyawat,1 Chalinee Monsereenusorn,2 Chanchai Traivaree2 1Division of Genetics, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand; 2Division of Hematology/Oncology, Department of Pediatrics, Phramongkutklao Hospital and College of Medicine, Bangkok, Thailand Background: Beta-thalassemia is one of the most common genetic disorders in Thailand. Clinical phenotype ranges from silent carrier to clinically manifested conditions including severe beta-thalassemia major and mild beta-thalassemia intermedia. Objective: This study aimed to characterize the spectrum of beta-globin gene mutations in pediatric patients who were followed-up in Phramongkutklao Hospital. Patients and methods: Eighty unrelated beta-thalassemia patients were enrolled in this study including 57 with beta-thalassemia/hemoglobin E, eight with homozygous beta-thalassemia, and 15 with heterozygous beta-thalassemia. Mutation analysis was performed by multiplex amplification refractory mutation system (M-ARMS, direct DNA sequencing of beta-globin gene, and gap polymerase chain reaction for 3.4 kb deletion detection, respectively. Results: A total of 13 different beta-thalassemia mutations were identified among 88 alleles. The most common mutation was codon 41/42 (-TCTT (37.5%, followed by codon 17 (A>T (26.1%, IVS-I-5 (G>C (8%, IVS-II-654 (C>T (6.8%, IVS-I-1 (G>T (4.5%, and codon 71/72 (+A (2.3%, and all these six common mutations (85.2% were detected by M-ARMS. Six uncommon mutations (10.2% were identified by DNA sequencing including 4.5% for codon 35 (C>A and 1.1% initiation codon mutation (ATG>AGG, codon 15 (G>A, codon 19 (A>G, codon 27/28 (+C, and codon 123/124/125 (-ACCCCACC, respectively. The 3.4 kb deletion was detected at 4.5%. The most common genotype of beta-thalassemia major patients was codon 41/42 (-TCTT/codon 26 (G>A or betaE accounting for 40%. Conclusion: All of the beta-thalassemia alleles have been characterized by

  6. Prevalence of metabolic syndrome in patients with minor beta thalassemia and its related factors: a cross-sectional study


    Gozashti, Mohammad Hossein; Hasanzadeh, Ali; Mashrouteh, Mahdieh


    Background Atherosclerotic disorders, hypertension and lipid profile alterations are of a lower prevalence in patients with minor beta thalassemia. On the other hand, nowadays, metabolic syndrome is considered as one of the major risk factors of developing cardiovascular diseases. Therefore, the present study was performed to determine the prevalence of metabolic syndrome in patients with minor beta thalassemia. Methods In this case-control study, body length, weight and waist circumference, ...

  7. Levels of Beta-2 Microglobulin and Cystatin C in Beta Thalassemia Major Patients

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    Ayse Kacar


    Full Text Available Aim: Thalassemia is accepted to be the most common genetic disease in the world. This study was performed to establish whether there was a glomerular renal damage, which was usually a less mentioned subject in patients with Beta Thalassemia Major, and to compare urea, creatinine and creatinine clearance with early indicators of kidney damage as Cystatin-C and %u03B2-2 microglobulin as on determining the glomerular damage. Material and Method: This study was prospectively performed in patients, who were regularly followed in the children hematology outpatient clinic with a diagnosis of Beta Thalassemia Major. Results: There was no statistically significant difference between urea and levels of creatinine clearance and Cystatin-C. There was a statistically negative relationship between creatinine and creatinine clearance at an advanced level as 53.7% (p: 0.002, p

  8. Prevalence and hematological characteristics of beta-thalassemia trait in Gaziantep urban area, Turkey. (United States)

    Gurbak, Mehmet; Sivasli, Ercan; Coskun, Yavuz; Bozkurt, Ali Ihsan; Ergin, Ahmet


    Thalassemia is one of the most common hereditary disorders in the Mediterranean region and studies have shown that the prevalence of beta-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 beta-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 beta-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 beta-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.

  9. [Neonatal expression of beta-thalassemia trait associated with hereditary spherocytosis in two monozygotic twins]. (United States)

    Ben Hamouda, H; Mahjoub, B; Soua, H; Laradi, S; Miled, A; Sfar, M T


    The beta-thalassemia trait is a heterozygous beta-thalassemia characterized by a partial deficiency of the synthesis of beta-globin chains of hemoglobin. It is usually asymptomatic and the diagnosis is often made on the occasion of the completion of a systematic blood count or a family survey. Clinical expression during the neonatal period is impossible and its association with hereditary spherocytosis is common. We report two monozygotic twins who, on the 3rd day of life, presented intense jaundice, unconjugated bilirubin associated with anemia, without hepatosplenomegaly. Laboratory tests found nonimmune hemolytic anemia with microcytosis and hypochromia justifying iterative blood transfusions. The etiological investigation found heterozygous beta-thalassemia associated with hereditary spherocytosis. The family investigation and molecular analysis objectified the beta-thalassemic mutation IVS1nt110 (G→A) in the heterozygous state in the twins, the father, the mother, and in one of the two brothers. With any nonimmune hemolytic anemia in newborns, the etiological investigation should be systematic for early diagnosis and to plan appropriate treatment.

  10. Rare association between two genetic conditions: turner syndrome and beta thalassemia minor

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    Full Text Available Rare disorders are defined as diseases, including those of genetic origin, which are life-threatening or chronically debilitating, which are of such low prevalence that special combined efforts are needed to address them. We present a case with a rare association between two genetic conditions: Turner phenotype and beta thalassemia minor. Turner syndrome is a chromosomal disorder that is characterized by the absence of all or part of a second sex chromosome in some or all cells. This condition occurs in 1 in 2,500 to 3,000 girls. The physical features include webbing of the neck, short stature, delayed growth of the skeleton, broad chest, cardivascular abnormalities and gonadal dysgenesis. Women with this disorder are usually infertile due to ovarian failure. The clinical diagnosis was confirmed by the cytogenetic and by FISH analysis, which revealed the presence of only one X chromosome. Treatment may include human growth hormone and estrogen replacement therapy. On the other hand, thalassemias are genetic conditions that result from imbalance in the normal coordinated synthesis of the globin subunits that make up the hemoglobin tetramer, leading to decreased and defective production of hemoglobin. Beta thalassemia syndromes are hereditary disorders characterized by a genetic deficiency in the synthesis of beta-globin chains. Beta thalassemia is inherited in an autosomal recessive manner. Thalassemia minor usually presents as an asymptomatic mild microcytic anemia, but our case also had splenomegaly and required splenectomy.

  11. Valores de ferritina sérica em beta talassemia heterozigota Serum ferritin levels in beta thalassemia carrier

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    Isabeth F. Estevão


    Full Text Available A low iron level, the commonest nutritional deficiency in the world, is a public health problem in developing countries. On the other hand, an excessive amount of iron is toxic, causing several organic dysfunctions, such as diabetes, cirrhosis, endocrinopathies and heart disease. Researchers have reported an association of iron overload with beta-thalassemia. The aim of this paper was to compare the serum ferritin levels of women with the beta-thalassemia trait. The results of serologic tests of 137 women of childbearing age were analyzed; 63 had the beta-thalassemia trait and 74 had Hb AA. In the beta-thalassemia carriers, the median ferritin value was 51.90 ng/mL and in the non-carriers 31.60 ng/mL (p = 0.0052. Levels of less than 20 and above 150 ng/mL were observed in 28% and 3% of the non-carriers and in 16% and 11% of the carriers, respectively. With these results it is possible to conclude that women in the reproductive age with the beta-thalassemia trait present higher ferritin levels in the northeastern region of São Paulo State. Further studies are necessary to clarify possible genetic and/or environment factors which interfere in iron absorption.

  12. Iron metabolism and ineffective erythropoiesis in beta-thalassemia mouse models. (United States)

    Ramos, Pedro; Melchiori, Luca; Gardenghi, Sara; Van-Roijen, Nico; Grady, Robert W; Ginzburg, Yelena; Rivella, Stefano


    beta-thalassemia is a disease associated with decreased beta-globin production leading to anemia, ineffective erythropoiesis, and iron overload. New mechanisms associated with modulation of erythropoiesis and iron metabolism have recently been discovered in thalassemic mice, improving our understanding of the pathophysiology of this disease. These discoveries have the potential to be translated into clinically-relevant therapeutic options to reduce ineffective erythropoiesis and iron overload. A new generation of therapies based on limiting ineffective erythropoiesis, iron absorption, and the correction of iron maldistribution could be on the way, possibly complementing and improving the current standard of patient care.

  13. Exploring the role of hepcidin, an antimicrobial and iron regulatory peptide, in increased iron absorption in beta-thalassemia. (United States)

    Breda, Laura; Gardenghi, Sara; Guy, Ella; Rachmilewitz, Eliezer A; Weizer-Stern, Orly; Adamsky, Konstantin; Amariglio, Ninette; Rechavi, Gideon; Giardina, Patricia J; Grady, Robert W; Rivella, Stefano


    To develop new treatments for beta-thalassemia, it is essential to identify the genes involved in the relevant pathophysiological processes. Iron metabolism in thalassemia mice being investigated, focusing on the expression of a gene called hepcidin (Hamp), which is expressed in the liver and whose product (Hamp) is secreted into the bloodstream. In mice, iron overload leads to overexpression of Hamp, while Hamp-knockout mice suffer from hemochromatosis. The aim of this study is to investigate Hamp in the mouse model of beta-thalassemia and to address the potential gene transfer of Hamp to prevent abnormal iron absorption.

  14. Molecular Identification Of Sicilian (deltabeta) Degrees-thalassemia Associated With Beta-thalassemia And Hemoglobin S In Brazil.



    We describe the clinical and molecular characteristics of two unrelated Brazilian families with an association of the Sicilian form of (deltabeta) degrees -thalassemia with hemoglobin S and beta-thalassemia. Direct sequencing of the beta-globin gene showed only the hemoglobin S mutation in patient 1 and the beta-thalassemia IVS1-110 in patient 2. The other allele was deleted in both patients and PCR of DNA samples of the breakpoint region of both patients showed a band of approximately 1,150 ...

  15. Beta-thalassemia mutations in Rome. A high frequency of the IVSII-745 allele in subjects of latium origin. (United States)

    Massa, A; Cianciulli, P; Cianetti, L; Iazzone, R; Cenci, A; Sorrentino, F; Franco, G; Pecci, G; Papa, G; Peschle, C


    We studied the molecular bases of beta-thalassemia in Rome, a city centrally located in Latium, which is a region with a low incidence of beta-carriers. People also come to Rome from other regions for specific or prenatal diagnostic assessment. Only 11 patients (20%) out of 62 characterized beta-thalassemia subjects were of Latium family origin. They presented five mutations with an uncommonly high frequency of the IVSII-745 allele, that was found in homozygosis in 4 unrelated patients from a southeastern area in the province of Frosinone. These data may indicate a founder effect.

  16. Prognostic factors in bone marrow transplantation for beta thalassemia major: experiences from Iran. (United States)

    Ghavamzadeh, A; Nasseri, P; Eshraghian, M R; Jahani, M; Baybordi, I; Nateghi, J; Khodabandeh, A; Sadjadi, A R; Mohyeddin, M; Khademi, Y


    This study concerns the effects of several pre-transplant features on outcome for patients with beta thalassemia major who underwent bone marrow transplantation (BMT). Seventy patients with beta thalassemia major underwent bone marrow transplantation during the period 1991-1997 in Shariati Hospital in Tehran, Iran. The survival and rejection curves levelled off at 8 and 18 months after transplantation at 82.6% and 11.4%, respectively. Pre-transplant clinical features (age, serum ferritin, portal fibrosis, hepatomegaly and quality of chelation therapy) were examined for their effects on survival and recurrence of thalassemia in this group of patients who were less than 16 years old. Increasing age, presence of portal fibrosis and increasing serum ferritin were significantly associated with reduced probability of survival (P = 0.0047, P = 0.016 and P = 0.024, respectively). Hepatomegaly and inadequate pre-transplant chelation therapy which were documented as poor prognostic factors in previous studies, were not evaluable in this study. We also showed the benefits of transplanting more than 5.5 x 10(8)/kg cells in this group of patients with no increase in complications.

  17. Hypoparathyroidism and intracerebral calcification in patients with beta-thalassemia major

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    Karimi, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Hematology Research Center, Department of Pediatrics, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Rasekhi, A.R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Rasekh, M. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Nabavizadeh, S.A. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Assadsangabi, R. [Iran-Shiraz-Namazee Hospital, Namazee Square, Imaging Research Center, Department of Radiology, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:; Amirhakimi, G.H. [Iran-Shiraz-Namazee Hospital, Namazee Square, Department of Endocrinology and Metabolism, Shiraz University of Medical Sciences, Shiraz (Iran, Islamic Republic of)], E-mail:


    Background: Hypoparathyroidism is one of the most important endocrine complications of thalassemia major. This study was conducted to evaluate the prevalence of intracerebral calcifications in patients with thalassemia with and without hypoparathyroidism. Methods: 47 beta-thalassemia patients with hypoparathyroidism underwent a brain CT scan to investigate the presence and extent of intracerebral calcification. 30 age- and sex-matched beta-thalassemic patients with normal parathyroid function who had undergone brain CT for headache, or some other minor neurologic problems were also enrolled in the study serving as controls. The amount of intracerebral calcification, hematologic parameters, and some clinical findings were compared between both groups. Results: Intracerebral calcification was present in 54.2% of beta-thalassemia patients with hypoparathyroidism. The most frequent sites of calcification were basal ganglia, and frontoparietal areas of the brain. Thalami, internal capsule, cerebellum and posterior fossa were other less frequently calcified regions of the brain. In contrast, there was no evidence of intracerebral calcifications in the 30 thalassemic patients with normal parathyroid function. There was not a statistically significant difference between serum ferritin concentrations in thalassemia patient with hypoparathyroidism and those with normal parathyroid function (2781 vs. 2178, P > 0.05). Conclusion: Intracranial calcification is a common finding in thalassemia patients with hypoparathyroidism, it can be extensive and involves most regions of the brain.

  18. beta-Thalassemia: HiJAKing Ineffective Erythropoiesis and Iron Overload. (United States)

    Melchiori, Luca; Gardenghi, Sara; Rivella, Stefano


    beta-thalassemia encompasses a group of monogenic diseases that have in common defective synthesis of beta-globin. The defects involved are extremely heterogeneous and give rise to a large phenotypic spectrum, with patients that are almost asymptomatic to cases in which regular blood transfusions are required to sustain life. As a result of the inefficient synthesis of beta-globin, the patients suffer from chronic anemia due to a process called ineffective erythropoiesis (IE). The sequelae of IE lead to extramedullary hematopoiesis (EMH) with massive splenomegaly and dramatic iron overload, which in turn is responsible for many of the secondary pathologies observed in thalassemic patients. The processes are intimately linked such that an ideal therapeutic approach should address all of the complications. Although beta-thalassemia is one of the first monogenic diseases to be described and represents a global health problem, only recently has the scientific community started to focus on the real molecular mechanisms that underlie this disease, opening new and exciting therapeutic perspectives for thalassemic patients worldwide.

  19. Decreased differentiation of erythroid cells exacerbates ineffective erythropoiesis in beta-thalassemia. (United States)

    Libani, Ilaria V; Guy, Ella C; Melchiori, Luca; Schiro, Raffaella; Ramos, Pedro; Breda, Laura; Scholzen, Thomas; Chadburn, Amy; Liu, YiFang; Kernbach, Margrit; Baron-Lühr, Bettina; Porotto, Matteo; de Sousa, Maria; Rachmilewitz, Eliezer A; Hood, John D; Cappellini, M Domenica; Giardina, Patricia J; Grady, Robert W; Gerdes, Johannes; Rivella, Stefano


    In beta-thalassemia, the mechanism driving ineffective erythropoiesis (IE) is insufficiently understood. We analyzed mice affected by beta-thalassemia and observed, unexpectedly, a relatively small increase in apoptosis of their erythroid cells compared with healthy mice. Therefore, we sought to determine whether IE could also be characterized by limited erythroid cell differentiation. In thalassemic mice, we observed that a greater than normal percentage of erythroid cells was in S-phase, exhibiting an erythroblast-like morphology. Thalassemic cells were associated with expression of cell cycle-promoting genes such as EpoR, Jak2, Cyclin-A, Cdk2, and Ki-67 and the antiapoptotic protein Bcl-X(L). The cells also differentiated less than normal erythroid ones in vitro. To investigate whether Jak2 could be responsible for the limited cell differentiation, we administered a Jak2 inhibitor, TG101209, to healthy and thalassemic mice. Exposure to TG101209 dramatically decreased the spleen size but also affected anemia. Although our data do not exclude a role for apoptosis in IE, we propose that expansion of the erythroid pool followed by limited cell differentiation exacerbates IE in thalassemia. In addition, these results suggest that use of Jak2 inhibitors has the potential to profoundly change the management of this disorder.

  20. Molecular mechanisms associated with increased fetal hemoglobin G gamma-type in part-aboriginal family with beta thalassemia. (United States)

    Motum, P I; Lammi, A; Trent, R J


    A part-Aboriginal family with beta thalassemia and raised hemoglobin F (HbF) was studied at the molecular level to determine if there were identifiable gene changes associated with increased production of HbF. Two beta thalassemia heterozygotes aged eight years and 18 months had raised HbF levels of 2.9% and 22% respectively. HbF was predominantly G gamma in composition. Five family members were typed for restriction fragment length polymorphisms (RFLPs) using nine restriction enzymes and five DNA probes specific for the beta globin cluster on chromosome 11. RFLPs were combined to construct haplotypes for the beta thalassemia and the high HbF defects. A beta globin subhaplotype comprising only 5' RFLP markers (-(+)-(+) +) co-segregated with the high HbF determinant. This has previously been associated with increased G gamma expression in beta thalassemia and sickle cell anemia. An additional Xmnl RFLP 5' to the G gamma gene, which has been described in individuals with elevated G gamma expression, was also demonstrated in those family members with increased G gamma levels. In this study both the 5' beta globin subhaplotype (-(+)-(+) +) and the Xmnl/gamma RFLP are present in the one family but the relative contributions of each cannot be determined.

  1. The effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients

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    Soleiman Mahjoub


    Full Text Available BACKGROUND: Thalassemia is the most common hereditary disease in the world. Thalassemic erythrocytes are exposed to higher oxidative stress and lipid peroxidation. The aim of this study was to investigate the effects of beta-carotene and vitamin E on erythrocytes lipid peroxidation in beta-thalassemia patients.
    METHODS: A prospective double-blind, placebo-controlled study of the effect of beta-carotene and vitamin E on lipid peroxidation in erythrocytes membranes was performed on 120 beta-thalassemia major patients in four groups. The patients were supplemented for 4 weeks as follows: group 1 with beta-carotene (13 mg/day, group 2 with vitamin E (550 mg/day, group 3 with beta-carotene plus vitamin E and group 4 with placebo. We prepared all capsules for 4 roups in the same shape and color. Measurements of serum beta-carotene and vitamin E were performed by high performance
    liquid chromatography. After preparation of ghost cells from blood specimens, malondialdehyde (MDA was determined as index of lipid peroxidation in erythrocytes membranes before and after treatment. RESULTS: The levels of serum beta-carotene and vitamin E were significantly lower and MDA concentrations in erythrocytes membranes were significantly higher in beta-thalassemia patients compared to controls (P<0.001. In groups that treated with vitamin supplements for 4-weeks, lipid peroxidation rates were significantly reduced after treatment (P<0.001, but in placebo group there was not significant difference (P>0.05.
    CONCLUSIONS: Our findings provide evidence that an oral treatment with beta-carotene and vitamin E can significantly reduce lipid peroxidation of erythrocytes membranes and could be useful in management of beta-thalassemia major patients. KEYWORDS: Beta-thalassemia major, beta-carotene, vitamin E, malondialdehyde, lipid peroxidation.

  2. Role of alpha-hemoglobin-stabilizing protein in normal erythropoiesis and beta-thalassemia. (United States)

    Weiss, Mitchell J; Zhou, Suiping; Feng, Liang; Gell, David A; Mackay, Joel P; Shi, Yigong; Gow, Andrew J


    Hemoglobin (Hb) synthesis is coordinated by homeostatic mechanisms to limit the accumulation of free alpha or beta subunits, which are cytotoxic. Alpha hemoglobin-stabilizing protein (AHSP) is an abundant erythroid protein that specifically binds free alphaHb, stabilizes its structure, and limits its ability to participate in chemical reactions that generate reactive oxygen species. Gene ablation studies in mice demonstrate that AHSP is required for normal erythropoiesis. AHSP-null erythrocytes are short-lived, contain Hb precipitates, and exhibit signs of oxidative damage. Loss of AHSP exacerbates beta-thalassemia in mice, indicating that altered AHSP expression or function could modify thalassemia phenotypes in humans, a topic that is beginning to be explored in clinical studies. We used biochemical, spectroscopic, and crystallographic methods to examine how AHSP stabilizes alphaHb. AHSP binds the G and H helices of alphaHb on a surface that largely overlaps with the alpha1-beta1 interface of HbA. This result explains previous findings that betaHb can competitively displace AHSP from alphaHb to form HbA tetramer. Remarkably, binding of AHSP to oxygenated alphaHb induces dramatic conformational changes and converts the heme-bound iron to an oxidized hemichrome state in which all six coordinate positions are occupied. This structure limits the reactivity of heme iron, providing a mechanism by which AHSP stabilizes alphaHb. These findings suggest a biochemical pathway through which AHSP might participate in normal Hb synthesis and modulate the severity of thalassemias. Moreover, understanding how AHSP stabilizes alphaHb provides a theoretical basis for new strategies to inhibit the damaging effects of free alphaHb that accumulates in beta-thalassemia.

  3. A Comparison of Quality of Life between Adolescences with Beta Thalassemia Major and their Healthy Peers

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    Shahram Baraz


    Full Text Available Background The chronic genetic blood disorder, thalassemia, affects Quality of life (QOL negatively. Regarding this, if adolescences with thalassemia are treated well, they will grow into an adult who will have a good potential for participating in society. Objectives: to determine the strongest predictor of QOL, compare QOL between the adolescents with beta-type major and their peers in Abadan city. Materials and Methods This was a cross-sectional study; the population consisted of 65 beta thalassemia major patients and 65  healthy peers with the same ages as the witness group. The data collection tools included SF-36 questionnaire and a questionnaire for demographic information. Data analysis was performed using independent t-test, correlation and linear regression by SPSS-16. Results The results of the study revealed that there is a significant difference (P < 0.05 in the average quality of life between the two groups of the study. On the other hand, the results showed that there was a meaningful relation between different aspects of life quality and family history of thalassemia            (P< 0.05. Also, there was a negative correlation between quality of life and the frequency of blood transfusion per year (P< 0.05. Conclusion Adolescences with beta thalassemia major do not have a desirable quality of life, therefore, this fact shows the necessity of serious reforming in various fields of health care, treatment, family, social and financial support, and rehabilitation that need more attention from health care policymakers.

  4. Common haplotype dependency of high G gamma-globin gene expression and high Hb F levels in beta-thalassemia and sickle cell anemia patients.


    Labie, D; Pagnier, J.; Lapoumeroulie, C; Rouabhi, F; Dunda-Belkhodja, O; Chardin, P; Beldjord, C; Wajcman, H; Fabry, M E; Nagel, R L


    We have studied 42 homozygous beta-thalassemia patients from Algeria and 34 sickle cell anemia patients from Senegal and Benin, determining the relationship between haplotypes, Hb F, and G gamma-globin/A gamma-globin ratios. Populations selected have a high frequency of haplotype homozygotes because of consanguinity (Algeria) and geographic homogeneity (West Africa). We find in beta-thalassemia patients, that haplotype IX in haplotypic homozygotes and heterozygotes, haplotype III in heterozyg...

  5. Utilization of denaturing gradient gel electrophoresis for diagnosis of {beta}-thalassemia and ascertainment of new mutations

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    Ngo, K.Y.; Liu, D.; Lee, J. [Univ. of California, San Diego (United States)] [and others


    During the past two years we have tested 2,300 Southeast Asians for alpha- and beta-thaleassemia mutations. We found the incidence of hemoglobin E ({beta}{sup 26}) to be 47% among Laotians and 38% among Cambodians. The incidence of beta thalassemia trait is 9% for Laotians and 6% for Cambodians. Thus, the risk for hemoglobin E/{beta}{sup 26} thalassemia, a transfusion-dependent disorder, is increased in these two population groups. Denaturing gradient gel electrophoresis (DGGE) has proven to be useful in testing for beta-thalassemia carriers and identifying new mutations in the beta globin gene. DNA was extracted from venous blood obtained from patients with elevated Hgb A2 (>4%). Five DNA fragments, encompassing the beta globin gene cluster, were amplified by PCR and analyzed, along with known beta gene mutations as controls, by DGGE using different denaturing gradient concentrations. Different mutations at the same nucleotide position can be distinguished by migration pattern on the DGGE (e.g., in IVS-I-1, G{r_arrow}A and T). Compound heterozygotes for {beta}-thalassemia can be detected on the same gel (e.g., HbE/mutation codon 17). New mutations are identified by their migration pattern compared with controls and determined by subsequent sequencing. We have identified three new mutations: codon 82 CAA{r_arrow}AAA in one Cambodian patient; IVS-II-667, T{r_arrow}C and IVS-II-672, A{r_arrow}C in two Laotian patients. When the parent`s genotypes are known, prenatal diagnosis can be obtained within 24 hours. Thus, PCR/DGGE combination is a rapid and reliable diagnostic approach to clinically significant {beta}-thalassemia. The most important steps are carefully designed primers and predetermined gradient concentrations for DGGE.

  6. Prevalence of Heart Failure in the Cases of Beta-thalassemia Major; Two Years Follow-Up

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    Atooshe Rohani


    Full Text Available Inroduction: Heart failure (HF is an important cause of morbidity and mortality in the cases of Beta-thalassemia major. The purpose of this study was to estimate HF prevalence in these patients and to assess the survivability of those who were treated with intensive chelating therapy. Design and methods: This cross sectional study included 72 beta-thalassemia major cases, the mean age at the time of referral was 15.7±6.2 years (range 6-35 years and were followed in a prospective 2 year study. A self-reporting symptom questionnaire was administered, a 12-lead ECG was taken and an echocardiography was obtained from all participants. Echocardiography was performed at 6 month intervals or when a new symptom developed. Results: Risk factors (except for iron overload in the study population were hypothyroidism and diabetes mellitus. The male to female ratio was0.75.Twelve patients had left ventricular (LV systolic dysfunction and 57,79% had LV diastolic dysfunction whereas 11,15% had RV failure. Fifty-nine (81% patients had cardiac disease of which diastolic dysfunction was the most common manifestation .Those with systolic dysfunction were older at presentation (22 ± 6 years versus 31 ± 4 years; P <0.001, and had the highest mean serum ferritin level (3,355 ± 1241 ng/mL versus 6,397 ± 1,613 ng/mL; P <0.001. The 2 year survival rate in patients with beta thalassemia in this study was 98%. Conclusions: Diastolic dysfunction is highly prevalent in even asymptomatic beta-thalassemia major patients. The high prevalence of diastolic dysfunction is indicative of a significant amount of the population who are at a high risk for HF

  7. Characterization of beta-thalassemia mutations in patients from the state of Rio Grande do Norte, Brazil

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    Zama Messala Luna da Silveira


    Full Text Available 35 unrelated individuals were studied for characterization as either heterozygous or homozygous for beta-thalassemia. Molecular analysis was done by PCR/RFLP to detect the mutations most commonly associated with beta-thalassemia (β0IVS-I-1, β+IVS-I-6, and β039. In the patients who showed none of these mutations, the beta-globin genes were sequenced. Of the 31 heterozygous patients, 13 (41.9% had the β+IVS-I-6 mutation, 15 (48.4% the β0IVS-I-1 mutation, 2 (6.5% the β+IVS-I-110 mutation and 1 (3.2% the β+IVS-I-5 mutation. IVS-I-6 was detected in the four homozygotes. The mutation in codon 39, often found in previous studies in Brazil, was not detected in the present case. This is the first study aiming at identifying mutations that determine beta-thalassemia in the state of Rio Grande do Norte.

  8. The pancreas in {beta}-thalassemia major: MR imaging features and correlation with iron stores and glucose disturbunces

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    Papakonstantinou, Olympia [University Hospital of Heraklion, Medical School of Crete, Department of Radiology, Heraklion, Crete (Greece); Attikon Hospital, 2nd Department of Radiology, Athens (Greece); Ladis, Vasilios; Kostaridou, Stavroula; Berdousi, Helen; Kattamis, Christos [Thalassemia Unit, University of Athens, ' ' Aghia Sophia' ' Children' s Hospital, Athens (Greece); Maris, Thomas; Gourtsoyiannis, Nicholas [University Hospital of Heraklion, Medical School of Crete, Department of Radiology, Heraklion, Crete (Greece)


    The study aims at describing the MR features of pancreas in beta-thalassemia major, investigating the relations between MR findings and glucose disturbances and between hepatic and pancreatic siderosis. Signal intensity ratios of the pancreas and liver to right paraspinous muscle (P/M, L/M) were retrospectively assessed on abdominal MR imaging studies of 31 transfusion-dependent patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 10 healthy controls, using T1- (120/4/90), intermediate in and out of phase - (120/2.7, 4/20), and T2*-(120/15/20) weighted GRE sequences. Using the signal drop of the liver and pancreas on opposed phase images, we recorded serum ferritin and results of oral glucose tolerance test (OGTT). Decreased L/M and P/M on at least the T2* sequence were noticed in 31/31 and 30/31 patients, respectively, but no correlation between P/M and L/M was found. Patients with pathologic OGTT displayed a higher degree of hepatic siderosis (p < 0.04) and signal drop of pancreas on opposed phase imaging (p < 0.025), implying fatty replacement of pancreas. P/M was neither correlated with glucose disturbances nor serum ferritin. Iron deposition in the pancreas cannot be predicted by the degree of hepatic siderosis in beta-thalassemia major. Fatty replacement of the pancreas is common and may be associated with glucose disturbances. (orig.)

  9. Hepatic iron overload and fibrosis in patients with beta thalassemia major after hematopoietic stem cell transplantation: A pilot study. (United States)

    Ghavamzadeh, Ardeshir; Mirzania, Mehrzad; Kamalian, Naser; Sedighi, Nahid; Azimi, Parisima


    Currently, hematopoietic stem cell transplantation (HSCT) is the only curative option for patients with beta-thalassemia major, but liver iron overload in these patients will not decrease and hepatic fibrosis may still progress despite successful HSCT. Liver biopsy samples were taken from 14 patients (Out of 25 patients) who underwent HSCT. All patients met three criteria: negative HCV antibody, liver fibrosis in samples before HSCT and lack of regular treatment for iron overload after HSCT (Because patients did not consent to phlebotomy or they had not regular follow-up). We evaluated liver fibrosis and liver iron overload by a semi quantitative method, Perls' Prussian blue staining, before and after HSCT. HSCT was successful in all the patients. Liver iron overload did not change after transplant (P=0.61), but hepatic fibrosis progressed after transplant (P=0.01). In patients with beta thalassemia major who previously had some degree of liver fibrosis, HSCT alone cannot reduce liver iron overload and liver fibrosis will increase. We recommend that regardless of the amount of iron overload in patients with beta thalassemia major that have shown some degree of fibrosis in their liver biopsy before transplantation, appropriate steps should be taken to reduce iron overload as soon as possible after successful transplantation.

  10. Resolution of alloimmunization and refractory autoimmune hemolytic anemia in a multi-transfused beta-thalassemia major patient

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    Joseph Philip


    Full Text Available Beta-thalassemia is one of the most prevalent autosomal disorders, which affect more than 400,000 newborn per year worldwide. In India, the carrier rate of beta-thalassemia varies from 3-17%. The overall rate of alloimmunization in thalassemia patients has been reported to be 5-30% in the world, which is mostly contributed by the alloimmunization to minor blood group antigen. Among Asians, the incidence of red cell alloimmunization is 22%. The recommended treatment for beta-thalassemia major is regular blood transfusion every 3 to 4 weeks. The development of anti-red cell antibodies (alloantibodies and/or autoantibodies can significantly complicate transfusion therapy. Alloantibodies are commonly associated with red cell hemolysis. Red cell autoantibodies appear less frequently, but they can result in clinical hemolysis called autoimmune hemolytic anemia (AIHA, and in difficulty in cross-matching blood. Patients with autoantibodies may have a higher transfusion rate and often require immunosuppressive drugs or alternative treatments including intravenous immunoglobulin (IVIg and rituximab (anti-CD20 monoclonal antibody.

  11. Psychological Aspects in Young Adults with Beta-Thalassemia Major, control group

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    S. H. Hosseini, M.D.


    Full Text Available Background and purpose: Beta-thalassemia major (TM, a chronic, genetically determined hematological disorder, has received little investigation on the psychological aspects of the disease and the psychosocial adjustment of patients with this anemia. In the present study, the aim was to explore the nature of psychopathology according to age, sex, school performance, severity and complications of the disease in TM patients compared with demographically matched healthy persons.Materials and Methods: A controlled anterograde cohort study was conducted at the Thalassemia Unit of Boo-Ali Hospital from June 2003 to November 2005 in Sari, Iran. Psychological aspects were evaluated by the Persian version of symptoms checklist-90-revised questionnaire. Information on relevant demographic characteristics, school performance, severity and complications of the disease was collected by one of the investigators who had created the questionnaire.Results: 125 persons with TM completed the questionnaires and were compared with 125 controls and 250 totally. The mean age of the participants was 18.51± 2.0 years and with a range of 15-25 years. 132 (52.8% were female with equal family status, social and economic status. Patients group reported a significantly lower level of marital status (P<0.01, education level (P<0.0001, school performance (P<0.0001. TM patients were found to have significantly more psychiatric disorders than the control subjects with GSI: 1.16 ± 0.47 vs. 1.01 ± 0.6; (P<0.03, PSD: 54.99 ± 12.59 vs. 46.42 ± 18.76 (P<0.0001, and PSDI 2.02±1.02 vs 2.45 ± 2.22 (P<0.05. We recorded significant changes in the mean scores of somatization (P<0.0001, interpersonal sensitivity (P<0.0001, depression (P<0.003, anxiety (P<0.05 and psychoticism (P<0.03 in the TM patients as compared to the control subjects.Conclusion: These findings show that beta-thalassemia major patients are at risk for psychiatric symptomatology and need appropriate psychiatric

  12. Cell and Gene Therapy for the Beta-Thalassemias: Advances and Prospects. (United States)

    Mansilla-Soto, Jorge; Riviere, Isabelle; Boulad, Farid; Sadelain, Michel


    The beta-thalassemias are inherited anemias caused by mutations that severely reduce or abolish expression of the beta-globin gene. Like sickle cell disease, a related beta-globin gene disorder, they are ideal candidates for performing a genetic correction in patient hematopoietic stem cells (HSCs). The most advanced approach utilizes complex lentiviral vectors encoding the human β-globin gene, as first reported by May et al. in 2000. Considerable progress toward the clinical implementation of this approach has been made in the past five years, based on effective CD34+ cell mobilization and improved lentiviral vector manufacturing. Four trials have been initiated in the United States and Europe. Of 16 evaluable subjects, 6 have achieved transfusion independence. One of them developed a durable clonal expansion, which regressed after several years without transformation. Although globin lentiviral vectors have so far proven to be safe, this occurrence suggests that powerful insulators with robust enhancer-blocking activity will further enhance this approach. The combined discovery of Bcl11a-mediated γ-globin gene silencing and advances in gene editing are the foundations for another gene therapy approach, which aims to reactivate fetal hemoglobin (HbF) production. Its clinical translation will hinge on the safety and efficiency of gene targeting in true HSCs and the induction of sufficient levels of HbF to achieve transfusion independence. Altogether, the progress achieved over the past 15 years bodes well for finding a genetic cure for severe globin disorders in the next decade.

  13. Beta thalassemia major: The effect of age on glomerular filtration rate

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    Majid Malaki


    Full Text Available Thalassemia is a common hereditary hemoglobinopathy disorder that affects many organs in the body. Estimation of kidney function is important, as it is the vital organ that plays the major role in the elimination of accumulated iron as well as the chelating drugs that have to be used as therapy. Sixty- three patients aged 1-29 years, with a mean ± SD of 14 ± 6.7 years, affected with beta- thalassemia major in Tabriz Children′s Hospital were evaluated for their renal function on the basis of their age, serum iron, serum ferritin and serum creatinine levels along with two methods of estimating glomerular filtration rate (GFR; by Schwartz method for those under 18 years old and using Modification of Diet in Renal Disease (MDRD formula for those who were 18 years and above. Elevation of serum creatinine denoting renal dysfunction was not seen in our patients, but hyperfiltration was a common finding. An increasing GFR was observed, which corresponded to age, but no relationships were seen between serum iron, serum ferritin, regular blood transfusion, chelating therapy to GFR.


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    Mohamed Bejaoui


    Full Text Available Beta-thalassemia major (TM remains to be one of the major health problems particularly in developing countries. Tunisia is a part of the Mediterranean countries mostly affected by this disease which is highly concentrated in small towns in families with low-income earners. The main objectives of this study are to provide a description of the demographic, clinical features and transfusion-related complications in patients with TM living in Tunisia. A standardized questionnaire was sent to clinicians throughout 33 different medical institutions caring for thalassemic patients. 391 transfusion dependant thalassemic patients with a median age of 10.7 years (range 3 months- 31 years were included in the study.The majority were originated from the north west of the country .A moderate overload between 1501 and 2500ng/ml was found in 61patients, while 81 patients (26.9% had ferritin level more than 2500 ng/ml and greater than 5000ng/ml in 21 patients (6.9%. 51 patients died from complications related to their disease. Heart failure was the main cause of death. The incidence of cardiac, endocrine, and infectious complications will be reviewed. Preventive measures such as health education, carrier screening and premarital screening remain the best ways for lowering the incidence of these diseases, which might be reflected in financial saving, social benefits and health benefits.

  15. New strategies to target iron metabolism for the treatment of beta thalassemia. (United States)

    Oikonomidou, Paraskevi Rea; Casu, Carla; Rivella, Stefano


    Iron is one of the most abundant elements in the Earth and a fundamental component of enzymes and other proteins that participate in a wide range of biological processes. As the human body has no mechanisms to eliminate the excess of iron, its metabolism needs to be tightly controlled in order to avoid all the sequelae associated with high iron levels. Iron overload is the main cause of morbidity and mortality in beta thalassemia. The master regulator of iron homeostasis, hepcidin, is chronically repressed in this disorder, leading to increased intestinal iron absorption and consequent iron overload. Many groups have focused on obtaining a better understanding of the pathways involved in iron regulation. New molecules have recently been synthesized and used in animal models of dysregulated iron metabolism, demonstrating their ability to target and reduce iron load. Antisense oligonucleotides, as well as lipid nanoparticle-formulated small interfering RNAs and minihepcidins peptides, are novel agents that have already proved to be efficient in modulating iron metabolism in mouse models and are therefore promising candidates for the treatment of patients affected by iron disorders.

  16. Globin gene transfer for treatment of the beta-thalassemias and sickle cell disease. (United States)

    Sadelain, Michel; Rivella, Stefano; Lisowski, Leszek; Samakoglu, Selda; Rivière, Isabelle


    The beta-thalassemias and sickle cell disease are severe congenital anemias that are caused by mutations that alter the production of the beta chain of hemoglobin. Allogeneic hematopoietic stem cell (HSC) transplantation is curative, but this therapeutic option is not available to the majority of patients. The transfer of a functional globin gene in autologous HCSs thus represents a highly attractive alternative treatment. This strategy, simple in principle, raises major challenges in terms of controlling the expression of the globin transgene, which ideally should be erythroid specific, differentiation-stage restricted, elevated, position independent, and sustained over time. Using lentiviral vectors, we have demonstrated that an optimised combination of proximal and distal transcriptional control elements permits lineage-specific, elevated expression of the beta-globin gene, resulting in therapeutic hemoglobin production and correction of anemia in beta-thalassemic mice. Several groups have now confirmed and extended these findings in various mouse models of severe hemoglobinopathies, thus generating enthusiasm for a genetic treatment based on globin gene transfer. Furthermore, globin vectors represent a general paradigm for the regulation of transgene function and the improvement of vector safety by restricting transgene expression to the differentiated progeny within a single lineage, thereby reducing the risk of activating oncogenes in hematopoietic progenitors. Here we review the principles underlying the genesis of regulated vectors for stem cell therapy.

  17. Abdominal Ultrasonographic Findings in Beta Thalassemia Major Patients in North of Iran

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    R. Abdi


    Full Text Available Background and Objective: High prevalence of tha-lassemia in the North of Iran is a major challenge of medical practitioners in this area. To investigate the prevalence of abdominal ultrasound findings in these patients, the present study was conducted. Materials and Methods: Two hundred patients (92 girls and 108 boys, all suffering from Beta thalas-semia major with a mean age of 14.5 years (ranging from 5 to 34 years were included in the study. Ab-dominal ultrasound examination was performed by two radiologists between 2001 and 2005 to detect sonographic findings in these patients. Results: Hepatomegaly was presented in 75% of these patients and splenomegaly was detected in 46% of them while 45% of cases had undergone splenec-tomy. Total incidence of gall bladder stone formation was 14% (15.5% in females and 11.9% in males and it had a direct correlation with the patients’ age. Lymphadenopathy of portohepatic and celiac area was detected in 138 (68% patients. In 4 patients ul-trasound revealed portal vein thrombosis whereas in the other 4 cases, splenic extramedullary hematopoi-esis was detected. Conclusion: This study revealed that a remarkable portion of patients had developed these complica-tions. Authors suggest ultrasound to be a part of rou-tine examinations in beta thalassemia major patients who receive multiple transfusions.

  18. [Long-term effects of combined therapy in patients with beta-thalassemia major]. (United States)

    Bagnulo, S; Giannini, A M; Moscatelli, F; Stragapede, L; Acquafredda, A; Dammacco, A


    We evaluated therapy complications in 19 beta-thalassemia major patients (mean age from 3 years/5 months and 1 years/6 months) who were followed at II Pediatric Department-University of Bari. 3 out of 19 patients underwent allogenic BMT from matched related donor; 2 out of 19 underwent splenectomy. All of them were receiving hypertransfusion therapy and continuous chelation with DFO. In all patients we performed physical examination, laboratory assays, cardiac and endocrinologic function tests, serum HBV-HCV-HIV antibodies, otoscopy and audiometric test, fundus oculi, skeletal x-ray. 1 out of 19 patients, who was under 15, had a slight dilatation of left ventricle and arythmia. All patients were HBsAb positive. 4/19 patients were HCV Ab positive (ELISA test) with an increase in ALT-AST serum levels since at least 6 months. In 3 of them we assessed RIBA test, always positive. 3 of them underwent liver biopsy (1 iron overload 2 chronic active hepatitis). All patients were HIV Ab negative. 4/15 patients revealed low GH levels after Arginina test. 13 pre-pubescent patients had normal results with GNRH test but lower results after FSH test. 1 pubescent patient had gonadotropic hypophyseal deficit. 4 patients had subclinic hypothiroidism. We couldn't find any sequelas in bone-eyes-ears. Hypertransfusion therapy, chelation, profilaxis of infections improved length and quality of life in thalassemic patients. Hypogonadotropic hypogonadism remains a serious sequela and we think it needs to be treated.

  19. Ineffective erythropoiesis in beta-thalassemia is characterized by increased iron absorption mediated by down-regulation of hepcidin and up-regulation of ferroportin. (United States)

    Gardenghi, Sara; Marongiu, Maria F; Ramos, Pedro; Guy, Ella; Breda, Laura; Chadburn, Amy; Liu, YiFang; Amariglio, Ninette; Rechavi, Gideon; Rachmilewitz, Eliezer A; Breuer, William; Cabantchik, Z Ioav; Wrighting, Diedra M; Andrews, Nancy C; de Sousa, Maria; Giardina, Patricia J; Grady, Robert W; Rivella, Stefano


    Progressive iron overload is the most salient and ultimately fatal complication of beta-thalassemia. However, little is known about the relationship among ineffective erythropoiesis (IE), the role of iron-regulatory genes, and tissue iron distribution in beta-thalassemia. We analyzed tissue iron content and iron-regulatory gene expression in the liver, duodenum, spleen, bone marrow, kidney, and heart of mice up to 1 year old that exhibit levels of iron overload and anemia consistent with both beta-thalassemia intermedia (th3/+) and major (th3/th3). Here we show, for the first time, that tissue and cellular iron distribution are abnormal and different in th3/+ and th3/th3 mice, and that transfusion therapy can rescue mice affected by beta-thalassemia major and modify both the absorption and distribution of iron. Our study reveals that the degree of IE dictates tissue iron distribution and that IE and iron content regulate hepcidin (Hamp1) and other iron-regulatory genes such as Hfe and Cebpa. In young th3/+ and th3/th3 mice, low Hamp1 levels are responsible for increased iron absorption. However, in 1-year-old th3/+ animals, Hamp1 levels rise and it is rather the increase of ferroportin (Fpn1) that sustains iron accumulation, thus revealing a fundamental role of this iron transporter in the iron overload of beta-thalassemia.

  20. Better differential diagnosis of iron deficiency anemia from beta-thalassemia trait

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    Fakher Rahim


    Full Text Available Objective: Iron deficiency anemia (IDA and beta-thalassemia trait (ß-TT are the most common forms of microcytic anemia. This study was conducted to compare the validity of various discrimination indices in differentiating β-TT from IDA by calculating their sensitivity, specificity and Youden's index.Methods: Totally 323 subjects (173 children and 150 adults with microcytic anemia were involved in this study. We calculated 10 discrimination indices in all patients with IDA and β-TT. We divided the patients into two different groups as younger or older than 10 years. Results: None of the indices showed sensitivity and specificity of 100% in the patients older than 10 years, and in the patients younger than 10 years, only Shine & Lal index showed sensitivity close to 90% and specificity of 100%. The most accurate discriminative index for patients younger than 10 years was Shine & Lal and for those older than 10 years it was RDW index. According to Youden's index, Shine & Lal and RBC count showed the greatest diagnostic value in patients younger than 10 years and RDW and RBC count indices in those older than 10 years. Conclusion: None of the indices was completely sensitive and specific in differentiation between β-TT and IDA. Mean and median mean cell Hb density (MCHD were very close to normal values in both IDA and β-TT patients, but in the case of mean density of Hb/liter (MDHL, we found that the mean and median were significantly higher than normal values in β-TT and lower than normal values in IDA patients. In our study, Youden's index of RBC and Shine & Lal were the highest and most reliable indices in differentiating β-TT from IDA in the patients younger than 10 years. For patients older than 10 years, the most reliable discrimination indices were RBC and RDW.

  1. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia

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    Murtadha Al-Khabori


    Full Text Available Objectives: Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX side effects in patients with thalassemia major or intermedia.Methods: A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period.Results: Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline, feeling unwell (2, severe diarrhea (1, pregnancy (1, death unrelated to chelator (2 and rise in serum transaminases (2. Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013.Conclusion: Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings.

  2. Side effects of Deferasirox Iron Chelation in Patients with Beta Thalassemia Major or Intermedia (United States)

    Al-Khabori, Murtadha; Bhandari, Sunil; Al-Huneini, Mohammed; Al-Farsi, Khalil; Panjwani, Vinodh; Daar, Shahina


    Objectives Chelating agents remain the mainstay in reducing the iron burden and extending patient survival in homozygous beta-thalassemia but adverse and toxic effects may increase with the institution and long term use of this essential therapy. This study aimed to estimate the incidence of deferasirox (DFX) side effects in patients with thalassemia major or intermedia. Methods A retrospective study of 72 patients (mean age: 20.3±0.9 yrs; 36 male, 36 female) with thalassemia major or intermedia treated at Sultan Qaboos University Hospital, Oman, was performed to assess the incidence of side effects related to deferasirox over a mean of 16.7 month follow-up period. Results Six patients experienced rashes and 6 had gastro-intestinal upset. DFX was discontinued in 18 patients for the following reasons: persistent progressive rise(s) in serum creatinine (7 patients; 40% mean serum creatinine rise from baseline), feeling unwell (2), severe diarrhea (1), pregnancy (1), death unrelated to chelator (2) and rise in serum transaminases (2). Three patients were reverted to desferoxamine and deferiprone combination therapy as DFX was no longer biochemically effective after 18 months of therapy. There was no correlation between baseline serum ferritin and serum creatinine or a rise in serum creatinine. Cardiac MRI T2* did not change with DFX therapy. However, there was an improvement in liver MRI T2* (p=0.013). Conclusion Renal side effects related to deferasirox appear to be higher than those reported in published clinical trials. Further larger studies are required to confirm these findings. PMID:23599881

  3. Prevalence of occult hepatitis C virus infection in Iranian patients with beta thalassemia major. (United States)

    Bastani, Mohammad-Navid; Bokharaei-Salim, Farah; Keyvani, Hossein; Esghaei, Maryam; Monavari, Seyed Hamidreza; Ebrahimi, Mojtaba; Garshasebi, Saba; Fakhim, Shahin


    Occult hepatitis C virus infection (OCI) is a new pathological form of chronic hepatitis virus (HCV) infection characterized by the presence of HCV RNA in liver biopsy and/or peripheral blood mononuclear cell (PBMC) specimens and the absence of HCV RNA and anti-HCV antibodies (Abs) in plasma samples. β-thalassemia major is a hereditary recessive blood disease with deficiency in the hemoglobin beta chain. Thalassemic patients need blood transfusion therapy; repeated blood transfusion increases the risk of viral blood-borne infection. The aim of this study was to determine the prevalence of OCI in Iranian patients with β-thalassemia major. From February 2015 to November 2015, a total of 147 Iranian patients with β-thalassemia major were enrolled in this cross-sectional study. After extraction of viral RNA from the plasma and PBMC samples, HCV genomic RNA in the specimens was amplified by RT-nested PCR using primers from the 5'-UTR. The HCV genotypes of the positive specimens were tested using the RFLP assay. To confirm the HCV genotypes, the 5'-UTR fragment was amplified and cloned into the pJET1.2/blunt cloning vector and then sequenced. Out of 147 patients, 106 (72.1 %) were negative for anti-HCV Abs and HCV RNA. HCV RNA was found in PBMC specimens of six (5.7 %) patients, from a total of 106 patients with undetectable plasma HCV RNA and anti-HCV Abs. Therefore, six out of 106 patients had OCI. HCV genotyping revealed that three patients were infected with HCV subtype 1b, two patients were infected with HCV subtype 3a, and one patient was infected with HCV subtype 1a. These results revealed that Iranian patients with beta-thalassemia major might have OCI. Therefore, it seems that the design of a study to identify this infection in patients with β-thalassemia major would provide valuable information.

  4. Genetic therapy for beta-thalassemia: from the bench to the bedside. (United States)

    Arumugam, Paritha; Malik, Punam


    Beta-thalassemia is a genetic disorder with mutations in the β-globin gene that reduce or abolish β-globin protein production. Patients with β-thalassemia major (Cooley's anemia) become severely anemic by 6 to 18 months of age, and are transfusion dependent for life, while those with thalassemia intermedia, a less-severe form of thalassemia, are intermittently or rarely transfused. An allogeneically matched bone marrow transplant is curative, although it is restricted to those with matched donors. Gene therapy holds the promise of "fixing" one's own bone marrow cells by transferring the normal β-globin or γ-globin gene into hematopoietic stem cells (HSCs) to permanently produce normal red blood cells. Requirements for effective gene transfer for the treatment of β-thalassemia are regulated, erythroid-specific, consistent, and high-level β-globin or γ-globin expression. Gamma retroviral vectors have had great success with immune-deficiency disorders, but due to vector-associated limitations, they have limited utility in hemoglobinopathies. Lentivirus vectors, on the other hand, have now been shown in several studies to correct mouse and animal models of thalassemia. The immediate challenges of the field as it moves toward clinical trials are to optimize gene transfer and engraftment of a high proportion of genetically modified HSCs and to minimize the adverse consequences that can result from random integration of vectors into the genome by improving current vector design or developing novel vectors. This article discusses the current state of the art in gene therapy for β-thalassemia and some of the challenges it faces in human trials.

  5. Beta-thalassemia and beta[A] globin gene haplotypes in Mexican mestizos. (United States)

    Villalobos-Arámbula, A R; Bustos, R; Casas-Castañeda, M; Gutiérrez, E; Perea, F J; Thein, S L; Ibarra, B


    B-globin haplotypes of 20 beta-thalassemia (beta-thal) and 87 beta(A) Mexican mestizo chromosomes were analyzed to ascertain the origin of the beta-thal alleles and the frequencies and distribution of the beta(A) haplotypes among northwestern Mexican mestizos. Sixteen beta-thal chromosomes carried six Mediterranean alleles [five codon 39 C-->T; two IVS1:1 G-->A; two IVS1:5 G-->A; three IVS1:110 G(A; one codon 11 (-T) and three (deltabeta)zero-thal]; the remaining four were linked to three rare alleles (two -28 A-->C and one each: -87 C-->T and initiation codon ATG-->GTG). Among the 87 beta(A) chromosomes, 17 different 5' haplotypes with frequencies for 1, 3, 2 and 5 of 39.0%, 17. 2%, 9.2% and 6.9%, respectively, were observed. The beta-haplotype analysis showed that 13 out of 16 Mediterranean chromosomes could easily be explained by gene migration; however, one codon 39 associated with haplotype 4 (----+ +-), one IVS1:1 with haplotype 1(+----++) and one IVS1:5 G-->A, may represent separate mutational events. Analysis of the rare alleles showed that the -28 A-->C mutation was associated with the commonest beta(A) haplotype in Mexican mestizos, Mediterraneans and the total world population; therefore an independent origin cannot be ruled out. The -87 C-->T and initiation codon ATG-->GTG were found with beta-haplotypes different from the reported ones, suggesting an indigenous origin.

  6. The Corellation Between Serum Ferritin and Cardiac Troponin I in Major Beta Thalassemia Children

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    Muhammad Ali Shodikin


    Full Text Available Major beta thalassemia (MBT is a hereditary disease which synthesies defects in beta chains of haemoglobin, it is causes red blood cell destruction and the symptoms of anemia. Red blood cell destruction, frequent blood transfusion and low adherence to routine use of iron chelator lead to iron accumulation in the heart, liver and endocrine organs. Accumulation of iron in the myocard can lead acute myocardial infarction. One of cardiac markers that had been used for the diagnosis of myocardial infarction was cardiac troponin I (cTnI. The aim of this research is find the correlation between serum ferritin levels and cTnI in MBT children. A descriptive analytic research was conducted using a cross sectional design. The subjects were divided into 2 groups, the MBT group and the control group. In both groups, the serum ferritin and cTnI levels ere evaluated. Data were analyzed using t-test and Pearson correlation test. Eleven children in the MBT group and 11 children in the control group were involved in this study. In the MBT group, the mean of serum ferritin and cTnI levels were 4292.5 µg/L and 0.20 ng/mL respectively. The mean of serum ferritin levels in the MBT group were higher than in the control and statistically significant (p= 0.0004. The mean of serum ferritin levels in the MBT group were higher than in the control and statistically significant (p= 0.0004. The mean of serum cTnI in the MBT group were higher than in the control, but statistically not significant (p= 0.82. In the MBT group, there was a weak corellation between serum ferritin and cTnI levels (r= 0.34.

  7. An intracranial extramedullary hematopoiesis in a 34-year-old man with beta thalassemia: a case report

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    Tabesh Homayoun


    Full Text Available Abstract Introduction Extramedullary hematopoiesis occurs in approximately 15% of cases of thalassemia. Intracranial deposits of extramedullary hematopoiesis are an extremely rare compensatory process in intermediate and severe thalassemia. Case presentation We present an unusual case of an intracranial extramedullary hematopoiesis with a choroid plexus origin in a 34-year-old Caucasian man with beta thalassemia intermedia, who presented with the complaints of chronic headache and rapid progressive visual loss. Conclusion An intracranial extramedullary hematopoiesis, although extremely rare, should be considered as a potential ancillary diagnosis in any thalassemic patient and therefore appropriate studies should be performed to investigate the probable intracranial ectopic marrow before any surgical intervention.

  8. Detection of four beta-thalassemia point mutations in Iranians using a PCR-ELISA genotyping system. (United States)

    Gill, Pooria; Forouzandeh, Mehdi; Eshraghi, Naser; Ghalami, Mostafa; Safa, Majid; Noori-Daloii, Mohammad-Reza


    Development of molecular techniques with analytical capability of mutation detection can realize the medical diagnosis of diseases and improve people's health. beta-Thalassemia is one of the most prevalent genetic disorders in Iran and using a simple and rapid test in laboratories for the mass screening and prenatal diagnosis is essential. Here, we described a simple method for rapid detection of four common beta-thalassemia point mutations in Iranians (IVS-II-1 (G-->A), IVS-I-5 (G-->C), FSC 8/9 (+G), IVS-I-110 (G-->A)) using a PCR-ELISA genotyping system. After DNA isolation from whole blood, a segment of beta-globin gene was amplified by DIG-labeling PCR. The DIG-labeled PCR amplicons were denatured and added to biotinylated normal probe (for normal gene allele) and mutant probe (for mutant gene allele). The hybrids were detected by colorimetric ELISA method. The optical densities obtained using normal and mutant probes with heterozygous PCR products were very similar. The optical densities obtained using mutant probes were higher than normal probes with homozygous PCR products. In vice versa, the optical densities obtained using normal probes were higher than mutant probes with normal PCR products. All the results demonstrated that the PCR-ELISA has similar specificity in comparison to the amplification refractory mutation system.

  9. Pituitary gland height evaluated by MR in patients with {beta}-thalassemia major: a marker of pituitary gland function

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    Argyropoulou, M.I.; Metafratzi, Z.; Efremidis, S.C. [Dept. of Radiology, Univ. of Ioannina (Greece); Kiortsis, D.N. [Dept. of Physiology, Univ. of Ioannina (Greece); Bitsis, S.; Tsatoulis, A. [Dept. of Internal Medicine, Univ. of Ioannina (Greece)


    In transfusion-dependent {beta}-thalassemia major, increased iron deposition in the pituitary gland has a cytotoxic effect leading mainly to hypogonadotropic hypogonadism. Our purpose was to assess in these patients the height of the pituitary gland and to evaluate whether it represents a marker of pituitary gland function. In 29 patients with {beta}-thalassemia major and 35 age- and gender-matched controls the pituitary gland height was evaluated in a midline sagittal scan using a spin echo T1-weighted (500/20 TR/TE) sequence. In all patients, an extensive endocrine evaluation was performed, including measurements of spontaneous and stimulated levels of gonadotropins, thyroid hormones, growth hormone, insulin-like growth factor, and adrenal hormones. The pituitary gland height was lower in thalassemic patients with hypogonadotropic hypogonadism (n=15) (mean 3.48; SD 0.46) than in the age- and gender-matched controls (mean 6.29; SD 0.77), (P<0.001). No statistically significant difference was found between thalassemic patients without hormone dysfunction (n=14) (mean 5.34; SD 1.52) and age- and gender-matched controls (mean 5.91; SD 1.06). We conclude that in thalassemic patients the pituitary gland height is an additional marker of pituitary gland function and might be useful in clinical management. (orig.)


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    adel abd elhaleim hagag


    Patients and Methods: This study was conducted on 40 children with beta thalassemia major under follow-up at Hematology Unit, Pediatric Department, Tanta University Hospital having serum ferritin level more than 1000 ng/ml and was divided in two groups. Group IA: Received oral Deferasirox (Exjade and silymarin for 6 months. Group IB: Received oral Deferasirox (Exjade and placebo for 6 months and 20 healthy children serving as a control group in the period between April 2011 and August 2012 and was performed after approval from research ethical committee center in Tanta University Hospital and obtaining an informed written parental consent from all participants in this research. Results: Serum ferritin levels were markedly decreased in group IA cases compared with group IB (P= 0.001. Conclusion: From this study we concluded that, silymarin in combination with Exjade can be safely used in treatment of iron-loaded thalassemic patients as it showed good iron chelation with no sign of toxicity. Recommendations: Extensive multicenter studies in large number of patients with longer duration of follow up and more advanced methods of assessment of iron status is recommended to clarify the exact role of silymarin in reduction of iron over load in children with beta thalassemia.

  11. Successful treatment of murine beta-thalassemia intermedia by transfer of the human beta-globin gene. (United States)

    May, Chad; Rivella, Stefano; Chadburn, Amy; Sadelain, Michel


    The beta-thalassemias are caused by more than 200 mutations that reduce or abolish beta-globin production. The severity of the resulting anemia can lead to lifelong transfusion dependency. A genetic treatment based on globin gene transfer would require that transgene expression be erythroid specific, elevated, and sustained over time. We report here that long-term synthesis of chimeric hemoglobin (mualpha(2):hubeta(A)(2)) could be achieved in mice with beta-thalassemia intermedia following engraftment with bone marrow cells transduced with a lentiviral vector encoding the human beta-globin gene. In the absence of any posttransduction selection, the treated chimeras exhibit durably increased hemoglobin levels without diminution over 40 weeks. Ineffective erythropoiesis and extramedullary hematopoiesis (EMH) regress, as reflected by normalization of spleen size, architecture, hematopoietic colony formation, and disappearance of liver EMH. These findings establish that a sustained increase of 3 to 4 g/dL hemoglobin is sufficient to correct ineffective erythropoiesis. Hepatic iron accumulation is markedly decreased in 1-year-old chimeras, indicating persistent protection from secondary organ damage. These results demonstrate for the first time that viral-mediated globin gene transfer in hematopoietic stem cells effectively treats a severe hemoglobin disorder.

  12. The "lively" cytokines network in beta-Thalassemia Major-related osteoporosis. (United States)

    Morabito, Nunziata; Russo, Giuseppina T; Gaudio, Agostino; Lasco, Antonino; Catalano, Antonio; Morini, Elisa; Franchina, Fabio; Maisano, Domenica; La Rosa, Mariangela; Plota, Maria; Crifò, Adolfa; Meo, Anna; Frisina, Nicola


    Osteoporosis affects approximately 40-50% of adult patients with beta-Thalassemia Major (beta TM). Recent data have implicated an altered modulation of the osteoprotegerin (OPG)/receptor activator of NFkB ligand (RANKL) system in the pathogenesis of beta TM-osteoporosis. OPG/RANKL system acts downstream from IL-1 alpha, IL-6 and TNF-alpha and it may be the final actor mediating the effects of these cytokines on the regulation of both postmenopausal and metabolic bone resorption. However, to date, there are no data on circulating levels of these pro-resorptive cytokines in beta TM patients. We investigated the potential relationships among these cytokines, several markers of bone turnover and bone mineral density (BMD) in beta TM patients. IL-1 alpha, IL-6 and TNF-alpha, OPG and RANKL serum levels, hemato-urinary bone remodeling markers and bone mineral density (BMD) at L2L4 and femoral neck as well as erythropoietin (EPO), 17beta-estradiol, and free-testosterone levels were measured in 30 well treated beta TM patients and in 20 healthy subjects, matched for age, sex and BMI with the patients. beta TM patients showed an altered bone turnover, with increased deoxypyridinoline (D-PYR) levels (P<0.0001), decreased osteocalcin (BGP) concentrations (<0.0001) and significantly lower lumbar (P=0.001) and femoral (P<0.05) BMD values as compared to controls. Circulating levels of IL-1 alpha (P<0.0001), TNF-alpha (P<0.0001) and IL-6 (P<0.05) were all increased in beta TM patients as compared with controls. In beta TM patients, IL-1 alpha was significantly related with D-PYR (r=0.5; P<0.05), RANKL (r=0.7; P=0.03) and IL-6 (r=0.3; P=0.006); IL-6 was also significantly correlated with D-PYR (r=0.5; P<0.05) and EPO levels (r=0.3; P=0.03); TNF-alpha showed a negative correlation with L2L4 BMD (r=-0.4; P<0.05). Our data demonstrate, for the first time, an association between increased circulating levels of pro-resorptive cytokines and an altered bone turnover in beta TM

  13. Detection of Left Ventricular Regional Function in Asymptomatic Children with beta-Thalassemia Major by Longitudinal Strain and Strain Rate Imaging

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    Ali Bay


    Full Text Available Objective: Cardiac failure due to iron overload remains the most common cause of death in patients with beta-thalassemia major. This study aimed to evaluate myocardial function in children with beta-thalassemia major using standard echocardiography technique and strain rate imaging. Materials and Methods: Conventional echocardiographic analysis, tissue velocity imaging, and strain/strain rate imaging of the left ventricle were evaluated in 48 children with beta thalassemia major (19 girls, 29 boys; 8.39±4.05 years and 22 healthy children (11 girls, 11 boys; 8±3.72 years. Results: Conventional echocardiographic examinations revealed that beta-thalassemia patients had larger left ventricular end-systolic diameter, end-diastolic and end-systolic volume, left ventricular mass index, and mitral early/late diastolic flow velocity ratio (p<0.05. Strain and strain rate imaging study of the basal lateral wall of the left ventricle was higher in patients than in controls, at p=0.035 and p=0.008, respectively. Conclusion: We found that superior systolic strain and strain rate imaging of the left ventricle indicated the presence of regional systolic function in the left ventricular wall. We suggest that left ventricle volume and mass index parameters might be more sensitive than the other conventional and strain/strain rate imaging parameters during childhood. However, the adulthood strain and strain rate imaging values may be lower than controls, exceeding the critical level of iron overload.

  14. Heterozygous beta-thalassemia and homozygous H63D hemochromatosis in a child: an 18-year follow-up. (United States)

    Miniero, Roberto; Tardivo, Irene; Roetto, Antonella; De Gobbi, Marco


    At age of 3.2 years routine blood analysis showed the presence of a beta-thalassemic trait with unexpected high level of serum iron and high transferrin saturation. Hematological follow-up confirmed the moderate degree of anemia and persisting high levels of iron indices throughout the years with a progressive increase of serum ferritin. At the age of 19 years the patient was diagnosed homozygous for HC63D HFE. The patient referred by us confirm the possibility of precocious alteration of iron indices in patients with heterozygosity for beta-thalassemia inherited together with HFE mutations. This observation suggests that any children with thalassemic trait with increased transferrin saturation and/or serum ferritin might be investigated for the presence of the hemocromatosis genes in order to detect the disease before any clinical manifestation and even before organ iron loading.

  15. Evaluation of the children with beta-thalassemia in terms of their self-concept, behavioral, and parental attitudes. (United States)

    Yalçn, Siddika Songül; Durmuşoğlu-Sendoğdu, Mine; Gümrük, Fatma; Unal, Selma; Karg, Eda; Tuğrul, Belma


    This study was planned to explore the self-concept, behavioral, and parental attitudes of the children with beta-thalassemia major, and the factors that affect them. The study was undertaken between January and June 2004 at the Hacettepe University Ihsan Doğramaci Children's Hospital, Pediatric Hematology Unit, Ankara and 43 voluntary children with beta-thalassemia major on regular blood transfusion and iron chelation treatment between the ages of 5.0 and 18.0 years were included into the study. Age, sex, birth order, school performance, hemoglobin value, serum ferritin levels, associated illness, splenectomy status, presence of thalassemic sibling or relatives, death of thalassemic relatives, place of residence, maternal and paternal education were recorded. Parental Attitude Research Instrument, Piers-Harris Self-Concept Scale, and Child Behavior Checklist were applied. Higher educated mothers have lower overprotection (P=0.009), parental discordance (P=0.044), and discipline scores (P=0.002) than lower educated mothers. In cases with death of thalassemic relatives, democratic/equality attitude scores were decreased (P=0.034). With stepwise multiple linear regression analysis, splenectomy, good school achievement, absence of death of thalassemic relatives, and serum ferritin levels were found to increase Piers-Harris Self-Concept Scale; however, total behavior problem score was found to decrease with increasing age, splenectomy and decreasing overprotection subscale of Parental Attitude Research Instrument scores. The self-esteem and behavior problems of children with thalassemia depended not only on the variables related exclusively to the child (age, school achievement) and the illness-associated conditions (splenectomy, serum ferritin levels) but also on the parental attitude (overprotection).

  16. Comparative Sero-Prevalence Investigation of Helicobacter Pylori Infection in Beta Thalassemia Major Patients, Referred to Taleghani Center, Gorgan, Iran

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    Hedayat Mofidi SM


    Full Text Available Background and objectives: Recurrent Abdominal Pain (RAP syndrome is acommon disorder, especially in children with beta thalassemia major. Thesepatients are predisposed to heart diseases which are caused byhemochromatosis (Iron overload, resulting in sudden death. Because of therole of Helico bacter pylori in causing abdominal pain and peptic ulcer, and inincreasing the risk or exacerbating of heart diseases, it can be important in betathalassemia major. This study aimed at determining the frequency of anti-H.pylori class IgA in patients suffered from beta thalassemia major.Material and Methods: In this descriptive-analytic Study, 132 betathalassemia major Patients and 135 healthy cases were matched by age, sexand ethnic as a control group. The sera were separated from clot in firstSeroepidemiology and along with the filled questionnaires sent toImmunology-hematology Laboratory of paramedical school, in which thesamples were tested by ELISA method with Diagnostic kit for anti-H.pyloriIgA and IgG classes detection. We analyzed the Data by chi square andIndependent T and Fisher tests.Results: the results show that the difference between the anti-H.pylori classIgA in case (22.7% and control group (17.8% is not significant (P=0.6, Butit is significant between anti-H.pylori IgG class, 81.8% for cases and 54.8%for controls (P<0.001.Conclusion: Based on the results, the rate of anti-H.P IgA class in case is1.131 times more than control group, which is not significant. On the otherhand , the rate of anti-H.P IgG is 1.478 times more than control group which issignificant.Key words: Thalassemia, Helicobacter pylori, Gorgan, Sero epidemiology

  17. Perfil de beta talassemia heterozigota obtido a partir de análise data mining em banco de dados The profile of beta thalassemia obtained by data mining analysis in a database

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    Ana L. B. Domingos


    Full Text Available Variations in the phenotypic expression of heterozygous beta thalassemia reflect the formation of different populations. To better understand the profile of heterozygous beta-thalassemia of the Brazilian population, we aimed at establishing parameters to direct the diagnosis of carriers and calculate the frequency from information stored in an electronic database. Using a Data Mining tool, we evaluated information on 10,960 blood samples deposited in a relational database. Over the years, improved diagnostic technology has facilitated the elucidation of suspected beta thalassemia heterozygote cases with an average frequency of 3.5% of referred cases. We also found that the Brazilian beta thalassemia trait has classic increases of Hb A2 and Hb F (60%, mainly caused by mutations in beta zero thalassemia, especially in the southeast of the country.

  18. Prevalence and Intensity of Depression in Mothers of Children with Beta-Thalassemia Major In Talghani Hospital of Gorgan, Iran

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    Nargesbeygom Mirbehbahani


    Full Text Available Background: Thalassemia is a chronic disease that it leads to psychological and social problems for parents. Mothers are at markedly increased risk of suffering from psychological distress and depression because they usually take on a considerable part of extra care that their children need.This study was designed to determine prevalence and intensity of depression in mothers with a thalassemic child. Material and Methods: In this cross – sectional study, 65 mothers of children with thalassemia major (case group and 65 mothers of children without thalassemia major (control group were assessed using the Beck Depression Inventory (BDI. Data were analyzed by using SPSS (v 16.0 for windows. Results: Prevalence of depression was significantly higher in case group than that in control group (84.6%vs. 56.9%, p <0.05. Moderate depression had a highest prevalence in the both groups (33.4% in case group and 30.8% in control group. Prevalence of severe depression in case group was markedly higher than that in control group (29.2% vs. 3.1% p<0.05. There was a significant difference between intensity of depression in mothers of case group that had another child with beta-thalassemia major (p<0.05. Conclusion: Mothers of children with thalassemia major are vulnerable to depression. They need psychosocial support to promote their health.

  19. Adrenal glands in beta-thalassemia major: magnetic resonance (MR) imaging features and correlation with iron stores

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    Drakonaki, Eleni; Papakonstantinou, Olympia; Maris, Thomas; Gourtsoyiannis, Nicholas [University Hospital of Heraklion, Department of Radiology, Heraklion (Greece); Vasiliadou, Artemis [Aghios Georgios Hospital of Chania, Thalassemia Unit, Chania (Greece); Papadakis, Alex [Venizelion Hospital of Heraklion, Thalassemia Unit, Heraklion (Greece)


    This study aimed at describing the magnetic resonance (MR) imaging features of the adrenal glands in beta-thalassemic patients and at investigating the relation between adrenal and hepatic siderosis. Adrenal signal intensity (SI) was retrospectively assessed on abdominal MR studies of 35 patients with beta-thalassemia major undergoing quantification of hepatic siderosis and 12 healthy controls, using T1- (120/4/90), intermediate - (120/4/20), and T2*- (120/15/20) weighted GRE sequences. Adrenal SI was graded as grade 0 (normal SI on all sequences), grade 1 (hypointensity on T2* alone), or grade 2 (hypointensity on at least T2*). Adrenal size was measured in the thalassemic patients and compared with normative data. Liver-to-muscle (L/M) SI ratios, expressing hepatic siderosis, were estimated on each sequence. Serum ferritin levels were recorded. Adrenal hypointensity (grades 1 and 2) was noted in 24/35 (68.6%) patients. L/M ratios correlated significantly with adrenal SI in all sequences. Patients with grade 1 and grade 2 adrenal SI had significantly decreased L/M ratios compared with grade 0. Serum ferritin correlated significantly with L/M values but not with adrenal SI. Adrenal size was within normal limits. Diffuse hypointensity in normal-sized adrenals is a common MR finding in beta-thalassemic patients and correlates with the degree of hepatic siderosis. (orig.)

  20. Bone marrow changes in beta-thalassemia major: quantitative MR imaging findings and correlation with iron stores

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    Drakonaki, Eleni E.; Karantanas, Apostolos H. [University Hospital of Heraklion, Radiology Department, Heraklion, Crete (Greece); Maris, Thomas G. [University of Crete, Department of Medical Physics, Heraklion, Crete (Greece); Papadakis, Alex [Venizelion General Hospital, Heraklion, Crete (Greece)


    The purpose of this study is to describe the MR imaging features of bone marrow in beta-thalassemia major and investigate their relation to ferritin, liver and spleen siderosis. Spinal bone marrow was prospectively assessed on abdominal MR studies of 40 transfused beta-thalassemic patients and 15 controls using T1-w, Pd, T2*-w Gradient Echo (GRE) and T1-w turbo Spin Echo (TSE) sequences. Signal intensity (SI) ratios of liver, spleen and bone marrow to paraspinous muscles (L/M, S/M, B/M respectively) and the respective T2 relaxation rates (1/T2) were calculated. Serum ferritin levels were recorded. Bone marrow hypointensity in at least T2*-w GRE sequence was noted in 29/40 (72.5%) patients. Eleven/40 patients exhibited normal B/M on all MR sequences. Five/40 patients had normal B/M and low L/M. B/M correlated with L/M in T1-w TSE sequence only (r = 0.471, p = 0.05). B/M correlated with S/M and mean ferritin values in all sequences (r > 0.489, p < 0.01 and r > - 0.496, p < 0.03 respectively). Marrow 1/T2 did not correlate with ferritin values or liver and spleen 1/T2. B/M in transfused beta-thalassemic patients is related to splenic siderosis and ferritin levels. Although marrow is usually hypointense, it may occasionally display normal SI coexisting with liver hypointensity, a pattern typical of primary hemochromatosis. (orig.)

  1. Spatial repolarization heterogeneity detected by magnetocardiography correlates with cardiac iron overload and adverse cardiac events in beta-thalassemia major.

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    Chun-An Chen

    Full Text Available BACKGROUND: Patients with transfusion-dependent beta-thalassemia major (TM are at risk for myocardial iron overload and cardiac complications. Spatial repolarization heterogeneity is known to be elevated in patients with certain cardiac diseases, but little is known in TM patients. The purpose of this study was to evaluate spatial repolarization heterogeneity in patients with TM, and to investigate the relationships between spatial repolarization heterogeneity, cardiac iron load, and adverse cardiac events. METHODS AND RESULTS: Fifty patients with TM and 55 control subjects received 64-channel magnetocardiography (MCG to determine spatial repolarization heterogeneity, which was evaluated by a smoothness index of QTc (SI-QTc, a standard deviation of QTc (SD-QTc, and a QTc dispersion. Left ventricular function and myocardial T2* values were assessed by cardiac magnetic resonance. Patients with TM had significantly greater SI-QTc, SD-QTc, and QTc dispersion compared to the control subjects (all p values<0.001. Spatial repolarization heterogeneity was even more pronounced in patients with significant iron overload (T2*<20 ms, n = 20 compared to those with normal T2* (all p values<0.001. Loge cardiac T2* correlated with SI-QTc (r = -0.609, p<0.001, SD-QTc (r = -0.572, p<0.001, and QTc dispersion (r = -0.622, p<0.001, while all these indices had no relationship with measurements of the left ventricular geometry or function. At the time of study, 10 patients had either heart failure or arrhythmia. All 3 indices of repolarization heterogeneity were related to the presence of adverse cardiac events, with areas under the receiver operating characteristic curves (ranged between 0.79 and 0.86, similar to that of cardiac T2*. CONCLUSIONS: Multichannel MCG demonstrated that patients with TM had increased spatial repolarization heterogeneity, which is related to myocardial iron load and adverse cardiac events.


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    Full Text Available BACKGROUND : Beta - thalassemia syndromes are a group of hereditary blood disorders characterized by reduced or absent beta globin chain synthesis , resulting in transfusion dependent severe anemia , leading to iron overload , resulting in hypothyroidism as the most common endocrine problem. OBJECTIVE : There is lack of information about frequency of hypothyroidism in thalassemic patients in ce ntral part of India , so this was undertaken to determine the frequency of hypothyroidism in patients suffering from homozygous ß - thalassemia and to study its correlation with serum ferritin and transfusion index. METHOD : This descriptive study included 60 diagnosed thalassemia major patients aged 2 - 18 years. Demographic data as well as history of blood transfusion , from which transfusion index was estimated , was taken. Serum total T3 , T4 and TSH by sandwich ELISA method using Eliscan kit , serum ferritin lev el by sandwich ELISA method using Accu - bind kit were measured from fasting blood sample. Hypothyroidism was defined by a TSH level >6.4μIU/ml. RESULTS: Study of the thyroid panel among all 60 patients showed a mean TSH level of 4.65±2.41 μIU/ml. Mean total T3 and total T4 levels were 1.35±0.48 ng/ml and 7.4±1.93 μg/dl respectively. Mean serum ferritin level was 557.25±198.66 ng/dl. Hypothyroidism was detected in 14 (23.33% out of 60 β thalassemia patients. Out of these , compensated hypothyroid (normal T3 a nd T4 with raised TSH was seen in 9 patients (15% and decompensated hypothyroid (Decrease T3 or T4 and Raised TSH was seen in 5 patients (8.33%. There was significant positive correlation of TSH levels with serum ferritin levels , age and transfusion in dex. However total T3 and total T4 did not show any correlation with serum ferritin levels , age or transfusion index. CONCLUSION : Hypothyroidism , are more common in second decade of life. Early recognition and hence prevention of these complications will d efinitely help to

  3. Sustained improvements in myocardial T2* over 2 years in severely iron-overloaded patients with beta thalassemia major treated with deferasirox or deferoxamine. (United States)

    Pennell, Dudley J; Porter, John B; Piga, Antonio; Lai, Yong-Rong; El-Beshlawy, Amal; Elalfy, Mohsen; Yesilipek, Akif; Kilinç, Yurdanur; Habr, Dany; Musallam, Khaled M; Shen, Junwu; Aydinok, Yesim


    Long-term controlled studies are needed to inform on the clinical benefit of chelation therapy for myocardial iron removal in transfusion-dependent beta thalassemia patients. In a 1-year nonrandomized extension to the CORDELIA study, data collected from patients with myocardial siderosis provided additional information on deferasirox or deferoxamine (DFO) efficacy and safety. Myocardial (m)T2* increased from baseline 11.6 to 15.9 ms in patients receiving deferasirox for 24 months (n = 74; geometric mean [Gmean ] ratio of month 24/baseline 1.38 [95% confidence interval 1.28, 1.49]) and from 10.8 to 14.2 ms in those receiving DFO (n = 29; Gmean ratio 1.33 [1.13, 1.55]; P = 0.93 between groups). Improved mT2* with deferasirox was evident across all subgroups evaluated irrespective of baseline myocardial (mT2* < 10 vs. ≥ 10 ms) or liver (LIC <15 vs. ≥15 mg Fe/g dw) iron burden. Mean LVEF was stable and remained within normal limits with deferasirox or DFO. Liver iron concentration decreased from high baseline values of 30.6 ± 18.0 to 14.4 ± 16.6 mg Fe/g dw at month 24 in deferasirox patients and from 36.8 ± 15.6 to 11.0 ± 12.1 mg Fe/g dw in DFO patients. The long-term safety profile of deferasirox or DFO was consistent with previous reports; serious drug-related AEs were reported in 6.8% of deferasirox and 6.9% of DFO patients. Continued treatment of severely iron-overloaded beta thalassemia patients with deferasirox or DFO led to sustained improvements in myocardial iron irrespective of high or low baseline myocardial or liver iron burden, in parallel with substantial improvements in liver iron ( identifier: NCT00600938).

  4. Hemoglobina C em homozigose e interação com talassemia beta Homozygous hemoglobin C and its interaction with beta thalassemia

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    Ivan L. Angulo


    Full Text Available A hemoglobina C (Hb C é originária do oeste da África e é detectada por migração lenta na eletroforese alcalina em acetato de celulose. Consiste na mutação do gene da globina beta no códon 6 (GAG-AAG, resultando na substituição do sexto aminoácido da cadeia beta da hemoglobina humana, o ácido glutâmico, pelo aminoácido lisina. A cromatografia de alto desempenho (HPLC separa completamente as frações C e A2, permitindo caracterizar a presença da interação com talassemia beta. Esta entidade (Hb CC, em homozigoze é considerada benigna em relação à doença falciforme, já que a falcização não faz parte de sua fisiopatologia. A raridade do diagnóstico C homozigoto e C talassemia beta nos pacientes portadores de hemoglobinopatias nos alertou para a necessidade de se conhecer melhor e estudar aspectos clínicos e hematológicos dos casos dessa mutação em homozigose e na interação com a talassemia beta no ambulatório de anemias do Centro Regional de Hematologia e Hemoterapia de Ribeirão Preto, SP, Brasil.Hemoglobin C (Hb C originated in the west of Africa and is detected by alkaline electrophoresis by slow migration in cellulose acetate. It consists of a mutation of the beta globin gene in codon 6 (GAG-AAG, resulting in a substitution of glutamic acid, the sixth amino acid of the beta string of the human hemoglobin, for lysine. High performance chromatography (HPLC separates the C and A2 fractions completely, allowing the characterization of the presence of interactions with thalassemia beta. This entity (Hb CC is considered benign in respect to sickle cell disease, as sickle cells are not part of its physiopathology. The rarity of the diagnosis of homozygous C and beta thalassemia in patients with hemoglobinopathies showed the necessity of studying clinical and hematologic aspects of the cases of this mutation in homozygosis carriers and the interaction with beta thalassemia in the anemias clinic of the Regional Blood

  5. Evaluating the role of indirect bilirubin, urobilinogen and Shine AND Lal index as an alternative screening tool for beta thalassemia minor

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    Ridham A. Khanderia


    Methods: The present study was conducted on 100 (n=100 subjects in blood bank, department of pathology, government medical college Rajkot, Gujarat, India. In first group 50 subjects (Thalassemia minor were selected while in second group 50 (n2=50 normal individuals from hospital staff were selected. Complete-haemogram, serum-direct, indirect and total bilirubin, urine urobilinogen and their sensitivity and specificity were calculated. Results: Of the 50 cases in test group, 41 had higher Indirect Bilirubin level (>0.7 mg/dl, 35 had high urobilinogen level (>1 mg/dl. In control group out of 50 cases, 3 had high indirect bilirubin levels, 4 had high urobilinogen levels. Indirect-bilirubin had sensitivity of 82%, specificity of 94%. Urobilinogen showed sensitivity of 70% and specificity of 92%. Conclusion: Indirect bilirubin and urine-urobilinogen is a valuable, cost-effective screening test for beta-thalassemia-trait with sensitivity and specificity comparable to RBC indices. [Int J Res Med Sci 2015; 3(3.000: 730-737

  6. Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families

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    Elisa Fermo


    Full Text Available Hereditary xerocytosis (HX is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. We report the clinical, haematological, and molecular characteristics of four patients from two unrelated Italian families affected by HX, associated with beta-thalassemia trait and heterozygous pyruvate kinase deficiency, respectively. Two patients had been splenectomised and displayed thrombotic episodes. All patients had iron overload in the absence of transfusion, two of them requiring iron chelation. The diagnosis of HX was confirmed by LoRRca Osmoscan analysis showing a left-shifted curve. PIEZO1 gene sequencing revealed the presence of mutation p.E2496ELE, showing that this is one of the most frequent mutations in this disease. The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. The study underlines the importance of a precise diagnosis in HX, particularly in view of splenectomy, and the need of a molecular confirmation of suspected RBC enzymopathy.

  7. Hereditary Xerocytosis due to Mutations in PIEZO1 Gene Associated with Heterozygous Pyruvate Kinase Deficiency and Beta-Thalassemia Trait in Two Unrelated Families (United States)

    Vercellati, Cristina; Marcello, Anna Paola; Zaninoni, Anna; van Wijk, Richard; Mirra, Nadia; Curcio, Cristina; Cortelezzi, Agostino; Zanella, Alberto; Barcellini, Wilma; Bianchi, Paola


    Hereditary xerocytosis (HX) is a rare disorder caused by defects of RBC permeability, associated with haemolytic anaemia of variable degree and iron overload. It is sometimes misdiagnosed as hereditary spherocytosis or other congenital haemolytic anaemia. Splenectomy is contraindicated due to increased risk of thromboembolic complications. We report the clinical, haematological, and molecular characteristics of four patients from two unrelated Italian families affected by HX, associated with beta-thalassemia trait and heterozygous pyruvate kinase deficiency, respectively. Two patients had been splenectomised and displayed thrombotic episodes. All patients had iron overload in the absence of transfusion, two of them requiring iron chelation. The diagnosis of HX was confirmed by LoRRca Osmoscan analysis showing a left-shifted curve. PIEZO1 gene sequencing revealed the presence of mutation p.E2496ELE, showing that this is one of the most frequent mutations in this disease. The concomitant defects did not aggravate the clinical phenotype; however, in one patient, the initial diagnosis of pyruvate kinase deficiency delayed the correct diagnosis of HX for many years and resulted in splenectomy followed by thrombotic complications. The study underlines the importance of a precise diagnosis in HX, particularly in view of splenectomy, and the need of a molecular confirmation of suspected RBC enzymopathy. PMID:28367341

  8. A multicenter prospective study on the risk of acquiring liver disease in anti-hepatitis C virus negative patients affected from homozygous beta-thalassemia. (United States)

    Prati, D; Zanella, A; Farma, E; De Mattei, C; Bosoni, P; Zappa, M; Picone, A; Mozzi, F; Rebulla, P; Cappellini, M D; Allain, J P; Sirchia, G


    Although the risk of transfusion-transmitted hepatitis has been recently reduced, transfusion-dependent beta-thalassemia patients may still develop liver disease due to viral infection or iron overload. We assessed the frequency and causes of liver dysfunction in a cohort of anti-hepatitis C virus (HCV) negative thalassemics. Of 1,481 thalassemics enrolled in 31 centers, 219 (14.8%) tested anti-HCV- by second-generation assays; 181 completed a 3-year follow-up program consisting of alanine-aminotransferase (ALT) measurement at each transfusion and anti-HCV determination by third-generation enzyme-immunoassay (EIA-3) at the end of study. Serum ferritin levels were determined at baseline and at the end of follow-up. Ten patients were anti-HCV+ by EIA-3 at the end of follow-up. Of them, seven were already positive in 1992 to 1993 when the initial sera were retested by EIA-3, one tested indeterminate by confirmatory assay, and two had true seroconversion (incidence, 4. 27/1,000 person years; risk of infection, 1/7,100 blood units, 95% confidence interval [CI], 1 in 2,000-1 in 71,000 units). At baseline, 67 of 174 thalassemics had abnormal ALT. Of those with normal ALT, seven subsequently developed at least one episode of moderate ALT increase (incidence, 24.6/1,000 person-years). All of the 20 patients with ferritin values >/=3,000 ng/mL had clinically relevant ALT abnormalities, as compared with 53 of 151 with <3,000 ng/mL (P < .005). Hepatic dysfunction is still frequent in thalassemics. Although it is mainly attributable to siderosis and primary HCV infection, the role of undiscovered transmissible agents cannot be excluded.

  9. Comparing prevalence of Iron Deficiency Anemia and Beta Thalassemia Trait in microcytic and non-microcytic blood donors: suggested algorithm for donor screening

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    Tiwari Aseem


    Full Text Available Background: The prevalence of microcytosis in donors and Iron Deficiency Anemia (IDA and Beta-Thalassemia trait (BTT in microcytic and non-microcytic donors has not been studied in India. The present study aims at finding the same. Materials and Methods: Initially 925 donor samples were evaluated on cell-counter. Of these, 50 were found to be microcytic. These were subjected to Ferritin and HbA2 determination. Subsequently, an additional 51, age-and-sex matched non-microcytic donor samples were selected to serve as controls. These were subjected to the same tests. Results: The prevalence of microcytosis was 5.4% (50/925. Among the microcytic donors, 52% were IDA, 36% BTT, 8% both, and 4% none. In case of non-microcytic donors 29.4% were IDA, 3.9% BTT, and 66.7% none. Conclusions: The study revealed a high prevalence of IDA and BTT in blood donors and a higher probability of finding these in the microcytic samples. This prompted authors to suggest an algorithm for screening of blood donors for IDA and BTT. The algorithm recommends doing an hemogram on all donor samples, routinely. Ferritin could be done only in microcytic samples. At levels lower than15 ng/ml, it is diagnosed as IDA, and therefore, HPLC is performed only for non-IDA samples with Ferritin levels higher than 15 ng/ml. By employing this algorithm, a substantial number of IDA and BTT could be diagnosed while keeping the number of Ferritin tests small and the number of HPLC tests even smaller and thus making it cost efficient.

  10. Effects of the anti-receptor activator of nuclear factor kappa B ligand denusomab on beta thalassemia major-induced osteoporosis

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    Mohamed A Yassin


    Full Text Available Introduction: Osteoporosis represents the second most common cause of endocrinopathy in patients with beta thalassemia major (BTM. Some drugs proved effective to reduce vertebral and non-vertebral fracture risk. Denosumab is a fully human monoclonal antibody to the receptor activator of nuclear factor kappa B ligand (RANKL, a member of the tumor necrosis factor receptor superfamily essential for osteoclastogenesis. The efficacy and safety of denosumab in BTM-induced osteoporosis has not been tested. Objective: To evaluate the efficacy and safety of anti-RANKL on the biochemical and radiological parameters of bone mineralization in patients with BTM-induced osteoporosis. Design: The study population was selected using the random sampling method from the patient′s database of our thalassemia clinic. Transfusion-dependent BTM patients above 18 years with no history of treatment with bisphosphonates were randomly selected. Bone mineral density (BMD of the lumbar spine (LS and right femoral neck (FN were measured by dual energy X-ray absorption (DEXA scan using a calibrated method. Independent factors likely to be associated with low bone mass were determined and included in the analysis to ascertain possible associations. Patients and Methods: We studied 30 patients with BTM-induced osteoporosis as per World Health Organization criteria (T Score of less than − 1.0 being defined as osteopenic and a T Score of less than − 2.5 being referred as osteoporotic. 19 males and 11 females aged between 18 and 32 years, with full pubertal development (Tanner′s stage 5 at the time of the study. Their mean serum ferritin concentration was 3557 ng ± 1488 ng/ml. Every patient underwent DEXA scan as a baseline and after 12 months of denosumab therapy. Biochemical evaluation including serum concentrations of creatinine, Na, K, calcium, phosphorus, parathormone, bone specific alkaline phosphatase and type 1 collagen carboxy telopetide (ICCT using enzyme

  11. Mutation analysis of beta thalassemia gene in Guangxi Zhuang Autonomous Region%广西壮族自治区β-地中海贫血基因突变分析

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    张强; 范歆; 何升; 唐燕青; 陈秋丽; 郑陈光


    目的 分析广西壮族自治区(简称广西)常见、罕见类型β-地中海贫血(简称地贫)基因突变的发生情况,为减少漏诊、误诊提供临床帮助.方法 2010年1月至2013年12月,选取在广西妇幼保健院就诊及转诊的可疑地贫患者42 770例,其中男性20 740例,女性22 030例.年龄范围在1个月~ 54岁.所有患者进行血常规,血红蛋白电泳,血清铁、铁蛋白筛查;筛查阳性患者通过反向点杂交(RDB)进行基因诊断;筛查阳性但基因诊断常见基因未发现突变位点的患者进行β珠蛋白基因扩增并测序.结果 42 770名可疑地贫患者中,共确诊地贫患者28 101例,其中β-地贫患者10 891例,包括β-地贫纯合子49例,杂合子10 718例,双重 杂合子124例;患者进行β珠蛋白基因扩增并测序后,发现14种南方常见类型地贫,7种罕见β-地贫突变类型,罕见地贫检出率为17.949%(7/39).结论 广西地区β-地贫突变类型复杂多样;常规地贫基因检测正常但有地贫表型的患者,应对其进行罕见地贫的检测,减少漏诊,以便更好地为临床开展地贫诊断提供帮助.%Objective To investigate the occurrence of regular and rare types of beta thalassemia in Guangxi,and to reduce the misdiagnosis and missed diagnosis.Methods Between Jan 2010 and Dec 2013,42 770 patients (20 740 males and 22 030 females,one month to fifty-four years old) from Maternal and Child Healthy Hospital of Guangxi,who were suspected with thalassemia were involved in this study.All these patients were went through the following screening tests:routine blood cell count,hemoglobin electrophoresis test,and serum iron and ferritin tests.Positive patients in the screening test would be taken gene diagnosis with regular reverse dot blot (RDB) method; negative patients in gene diagnosis but positive in the screening test would be under the test of beta globin gene sequencing.Results Totally 28 101 patients were confirmed with thalassemia from 42

  12. Developmental effect of the XmnI site on Ggamma-globin gene expression among newborn Hb F-Malta-I [Ggamma117(G19)His-->Arg, CAT-->CGT] heterozygotes and adult beta+ -Thalassemia homozygotes. (United States)

    Pulis, Svetlana; Scerri, Christian A; Wismayer, Pierre Schembri; Galdies, Ruth; Wettinger, Stephanie Bezzina; Felice, Alex E


    Hb F-Malta-I [Ggamma117(19)His-->Arg, CAT-->CGT] is a stable and benign variant of Hb F found in 1.8% of Maltese newborn. We studied 120 Hb F-Malta-I heterozygotes and four Hb F-Malta-I homozygotes. The mean proportion of Ggamma-F-Malta-I in Hb F was 0.26 +/- 0.03 for the Hb F-Malta-I heterozygotes and 0.58 +/- 0.06 for the Hb F-Malta-I homozygotes. The Hb F-Malta-I allele was shown to occur on a background of the common Mediterranean haplotype Va [+ + - - - - - + + -]. Furthermore, the common Mediterranean haplotypes Va, IIIb [- + + + - + + + + -], I [+ + - - - - - + + +] and II [- + - + + - + + + +] accounted for most (66.2%) of the wild-type alleles among the tested Hb F-Malta-I heterozygotes. Different genotypes at the 5' epsilon HincII, Ggamma and Agamma HindIII, and 3'psibeta HincII sites (but not at the 5' Ggamma XmnI site) were found to be linked to significant variations in the proportion of Ggamma-F-Malta-I and Ggamma-globins in the Hb F of newborn Hb F-Malta-I heterozygotes. Moreover, the 5' Ggamma XmnI site was found to be associated with variations in Hb F and Ggamma-globin levels in a population of adult Maltese beta-thalassemia (thal) homozygotes. This implies that a determinant linked to the XmnI site which effects Ggamma-globin gene expression is active in anemic adults but not in normal infants.

  13. Extraosseous radiotracer uptake on bone scan in beta-thalassemia: report of one case; Fixation extraosseuse du radiotraceur lors de la realisation d'une scintigraphie du squelette chez un patient atteint de beta-thalassemie: a propos d'un cas

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    Guezguez, M.; Nouira, M.; Sfar, R.; Chatti, K.; Ben Fradj, M.; Ben Ali, K.; Ajmi, S.; Essabbah, H. [CHU Sahloul, Service de Medecine Nucleaire, Sousse (Tunisia); Zrour, S. [EPS F. Bourguiba, Service de Rhumatologie, Monastir (Tunisia)


    Red blood cell transfusion, main therapeutic modality of beta-thalassemia, leads to iron overload which may perturb several metabolic ways. The aim of this paper is to illustrate the uptake abnormalities observed on bone scan of thalassaemic patients and to discuss mechanisms of extraosseous accumulation of the radiopharmaceutical in this pathology. We report a 16-year-old child suffering from beta-thalassemia major undergoing transfusion therapy. A bone scan was indicated to look for osseous infection. This study revealed a little skeletal uptake and abnormal liver, splenic and renal accumulation. A repeat bone scan, performed three weeks later showed a better skeletal uptake which enabled the discovery of focal abnormalities and made the diagnostic easier. The effect of iron overload on radiopharmaceuticals uptake in bone scan is known since 1975. Dissociation of {sup 99m}Tc from the carrier ligand due to the presence of iron excess seems the most plausible hypothesis. Free {sup 99m}Tc can be bound to other tissular substrates which can explain extraosseous uptake. The normally available pool for bone is reduced and then the skeletal uptake decreased. This report limits considerably the sensitivity of the bone scan. A well-led iron chelation and eventually the use of diuretic drug may guarantee a better quality of bone scan images. (authors)

  14. Interação entre Hb C [beta6(A3Glu>Lys] e IVS II-654 (C>T beta-talassemia no Brasil Hb C [beta6(A3Glu>Lys] and IVS II - 654 (C>T beta thalassemia interaction in Brazil

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    Claudia R. Bonini-Domingos


    Full Text Available Thalassemias are a heterogeneous group of inherited disorders characterized by a microcytic hypochromic anemia and an imbalance in the synthesis of the globin-chains. Hb C is the second most frequently variant of hemoglobin found in Brazil. The laboratory diagnosis of hemoglobinopathies, including thalassemias, is growing in importance, particularly because of an increasing requirement for neonatal diagnosis of abnormal hemoglobins. Screening tests were carried out using alkaline and acid electrophoresis, globin-chain analysis by cellulose acetate in alkaline pH, isoelectric focusing and HPLC. The molecular characterization was made by PCR-ASO for Hb C and beta thalassemia mutants. Large-scale screening and discriminative methodologies must provide information about the hemoglobin polymorphisms in Brazilian population. HPLC is a powerful tool in these cases. Molecular characterization is important to genetic counseling and clinical management, in particular for the Brazilian population that have an intense racial admixture, with great variability of hemoglobins. In this paper an association between Hb C and beta thalassemia (IVS-II-654 in a black family from Brazil was described.

  15. Effects of beta-thalassemia minor on the efficacy of erythropoietin in hemodialysis patients%β地中海贫血对血液透析患者使用重组人促红细胞生成素疗效的影响

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    黄俊; 张虹; 傅君舟


    Objective To investigate the effects of beta - thalassemia minor on the efficacy of erythropoietin to ameliorate anemia in hemodialysis patients. Methods The hemodialysis patients with beta - thalassemia minor ( thalasse-mic group ) and the matched hemodialysis patients without beta - thalassemia minor ( control group ) were initially treated with erythropoietin [ 120 ~ 150 IU/( kg · week ) ] subcutaneous injection for three months. After three months of treatment , a high dose of erythropoietin [ 200 ~ 250 IU/( kg · week ) ] was applied for followed three months, if the hemoglobin levels less than 110 g/L in thalassemic group. Results There was no significant difference revealed in baseline hemoglobin level and therapeutic erythropoietin dose between thalassemic group and control group. However, the hemoglobin level of patients in thalassemic group was significantly lower than that in control group at each ends of the three months ( P 0.05),但每月末地贫组血红蛋白水平明显比对照组低(P<0.01);3个月后,对照组患者贫血基本纠正,而地贫组患者血红蛋白水平虽比治疗前有所改善(P<0.01),但贫血未能纠正.后3个月地贫组患者使用大剂量rHuEPO治疗,血红蛋白水平从第1月末开始明显上升(P<0.01),并持续至第3月末,患者贫血得以纠正;期间除引起患者血压升高外未出现不可控制的恶性高血压、内瘘堵塞等严重并发症.结论 β地中海贫血会影响血透患者使用rHuEPO改善贫血的疗效,大剂量rHuEPO能纠正伴β地中海贫血的血透患者贫血.

  16. The identification of beta-thalassemia mutants in Brazilians with high Hb F levels Identificação de mutantes de beta talassemia em grupo de indivíduos com Hb Fetal aumentada da população brasileira

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    Paula J. A. Zamaro


    Full Text Available Hemoglobinopathies are a heterogeneous group of genetic disorders which represent a public health problem, with significant morbidity, in countries where the prevalence is high. This study aimed at identifying molecular abnormalities that might explain the laboratorial profile obtained using electrophoresis and high performance liquid chromatography in a group of individuals without signs or clinical symptoms of anemia. Five different mutations for beta-thalassemia were found using PCR-ASO: three cases with CD 6 (-A, one CD 39, one IVI I-6, one -87 (mutations originating in the Mediterranean region and one IVS II-654 (mutation originating in Asia. This is the first time that the CD 6 (-A, -87 and IVS II-654 mutations have been described in the Brazilian population.As hemoglobinopatias são um grupo de afecções genéticas que representam problema de saúde pública em muitos países em que sua incidência é alta, com significativa morbidade. Objetivamos identificar defeitos moleculares que pudessem explicar o perfil laboratorial obtido por eletroforese e HPLC com Hb F elevada, em um grupo de indivíduos adultos sem sinais ou sintomas de anemia. Encontramos cinco diferentes mutações que originam beta talassemia por PCR-ASO: três casos com CD 6 (-A, um CD 39, um IVS 1-5, um -87 todas de origem mediterrânea, e um IVS II-654 de origem asiática. As mutações CD 6 (-A, -87 e IVS II-654 foram descritas pela primeira vez na população brasileira.

  17. 地拉罗司治疗重型β-地中海贫血铁过载的三年临床试验研究%A 3-year clinical trial of deferasirox in heavily iron-overloaded patients with Beta-thalassemia major

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    刘容容; 赖永榕; 马劼; 张新华; 罗建明; 李辉萍; 梁金清; 李喆; 王明月; 苏鹏


    Objective To evaluate the efficacy and safety of deferasirox in heavily iron-overloaded patients with beta-thalassemia major. Methods A single arm, open-label clinical trial was conducted to evaluate the efficacy and safety of deferasirox in the treatment for 23 patients with beta-thalassemia major and heavily iron-overloaded in 3 years follow-up. Results The 23 patients never received regular chelation before enrolling this trial [the mean baseline of serum ferritin was (5433.96 ± 2873.90) μg/L]. In this trial, a deferasirox dose of 20 mg·kg-1·d-1 could stabilize serum ferritin levles,while of ≥30mg·d-1 reduced the levels and achieved negative iron balance. There were no serious adverse events related to the drug.Most common adverse events were mild increases of liver enzyme and serum creatinine levels. Overall, 23 patients could tolerate the drug on schedule and all completed the trial. Conclusion As a new oral iron chelator, deferasirox has a significant efficacy for the treatment of iron overload. The effectiveness is dependent on the courses of treatment and the dose of deferasirox. The single-dose used is safe and tolerated, so deferasirox can remarkably improve life quality of patients.%目的 评价新型口服铁螯合剂--地拉罗司治疗重型β-地中海贫血(β-地贫)患者铁过载的疗效及安全性.方法 采用单组、开放试验设计,观察23例重型β-地贫铁过载患者3年随访中地拉罗司的疗效及安全性.结果 入组的23例重型β-地贫患者治疗前均未规则使用铁螫合剂,铁过载状况严重[血清铁蛋白平均基线值为(5433.96±2873.90)μg/L].20 mg·kg-1·d-1的地拉罗司能维持患者铁过载处于平衡状态,治疗前后血清铁蛋白水平无显著性变化;随治疗时间的延长,服药剂量的增加,≥30 mg·kg-1·d-1的地拉罗司能使患者铁过载达到负平衡状态,治疗前后比较血清铁蛋白水平差异具有统计学意义(P<0.01).3年随访中未出现地拉罗

  18. Hemoglobin Interlaken in combination with beta thalassemia trait

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    Mara J. Ojeda


    Full Text Available We report a rare a1 globin gene variant (Hb Interlaken found in a 63-year-old woman of Italian ancestry living in Buenos Aires Province, Argentina. The variant, a missense mutation at cd15 (GGT → GAT causing a Gly →Asp amino acid substitution and also known as Hb J Oxford, was found in combination with the common thalassemia trait cd 39 (C→T. The clinical picture of the patient was that of a b-thalassemia trait. 我们曾报道在阿根廷布宜诺斯艾利斯一名63岁意大利血统的妇女体内发现罕有的1珠蛋白基因(因特拉肯血红蛋白)变体。研究发现该变体是导致Gly → Asp氨基酸置的错义突变,也称为Hb J Oxford,与常见的地中海贫血性症cd 39 (C → T)有关。该患者临床症状与乙型地中海贫血特征相同。

  19. A preclinical approach for gene therapy of beta-thalassemia. (United States)

    Breda, Laura; Kleinert, Dorothy A; Casu, Carla; Casula, Laura; Cartegni, Luca; Fibach, Eitan; Mancini, Irene; Giardina, Patricia J; Gambari, Roberto; Rivella, Stefano


    Lentiviral-mediated beta-globin gene transfer successfully treated beta-thalassemic mice. Based on this result, clinical trials were initiated. To date, however, no study has investigated the efficacy of gene therapy in relation to the nature of the different beta-globin mutations found in patients. Most mutations can be classified as beta(0) or beta(+), based on the amount of beta-globin protein produced. Therefore, we propose that a screening in vitro is necessary to verify the efficacy of gene transfer prior to treatment of individual patients. We used a two-phase liquid culture system to expand and differentiate erythroid progenitor cells (ErPCs) transduced with lentiviral vectors. We propose the use of this system to test the efficiency of lentiviral vectors carrying the human beta-globin gene, to correct the phenotype of ErPCs from patients preparing for gene therapy. This new approach might have profound implications for designing gene therapy and for understanding the genotype/phenotype variability observed in Cooley's anemia patients.

  20. Approaches to management of beta-thalassemia intermedia

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    Joseph E. Maakaron


    Full Text Available Thalassemia intermedia is a genetically diverse group of diseases that is the result of an imbalance in the production of the alpha and beta chains with ensuing chronic hemolysis, ineffective erythropoiesis, and iron overload.Resulting complications include bone changes, hypercoagulability, and end-organ damage due to iron overload. This decade has witnessed major breakthroughs in the management of thalassemia. In this article, we examine these novelties in therapy including iron chelation therapy, stem cell transplant, and gene therapy.Iron chelation therapy has been revolutionized with the advent of deferasirox, a once-daily oral iron chelator, that has been shown to be safe and efficacious.Gene therapy was also at the core of this revolution with the discovery of novel gene elements and viral vectors allowing for better control and improved outcomes.

  1. Laboratory assessment of iron status and reticulocyte parameters in differential diagnosis of iron deficiency anemia and heterozygous beta-thalassemia Avaliação laboratorial do estado do ferro e parâmetros reticulocitários no diagnóstico diferencial da anemia ferropriva e beta-talassemia heterozigótica

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    Gisélia A.F.M. de Lima


    Full Text Available Introduction:The soluble form of transferrin receptor (sTfR has been pointed as a useful parameter to assess the iron status and erythropoiesis activity. Immature reticulocytes present high concentration of membrane transferrin receptor. We tested the correlation between sTfR and reticulocyte parameters in iron deficiency anemia (IDA and heterozygous beta-thalassemia (hetero beta-thal patients. Laboratory parameters related to iron status and reticulocytes were studied in order to establish their clinical value to distinguish both anemias. Material and Methods: Reticulocyte measurements were obtained using a semi-automated analyzer and serum concentration of sTfR was determined by an immunoenzymatic technique. Forty-nine IDA and 43 hetero beta-thal patients were studied. Results: Reticulocyte count and sTfR values were significantly higher in IDA than in hetero beta-thal group, but the best parameter to distinguish both anemias was sTfR index, obtained by the ratio sTfR/ferritin level. Transport compartment was better evaluated by transferrin dosage than by transferrin iron binding capacity (TIBC determination. The association of serum iron with transferrin measurements (transferrin index improved the accuracy of the transferrin test. Discussion: The correlation between highly immature reticulocytes and sTfR level was observed only in IDA group, suggesting that cellular iron deprivation is the main responsible factor for up regulation of the sTfR synthesis in immature red blood cells. High sTfR values in hetero beta-thal patients reflect a degree of ineffective erythropoiesis in this hemoglobinopathy. Conclusion: We concluded that sTfR, ferritin and transferrin measurements are useful and precise parameters to discriminate IDA from hetero beta-thal patients.Introdução: A forma solúvel do receptor da transferrina (sTfR tem sido indicada como um parâmetro útil na avaliação do estado do ferro e da atividade eritropoiética. Reticul

  2. Prevalence of renal tubular dysfunction in beta thalassemia minor in shiraz

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    Ali Moradi Nakhodcheri


    Full Text Available  Background & objective: β-Thalassemia minor is an asymptomatic hereditary disease. The first study on the relation of renal tubular dysfunction and β-thalassemia minor was performed in 2002 but those studies seem inadequate.The main goal of this study is through evaluation of renal tubular function in 100 patients with thalassemia minor. Materials & Methods: 100 patients with β- thalassemia which confirmed by hemoglobin electrophoresis and CBC as well as RBC indices were studied.14 out of 100 cases exit because of Urinary Tract Infection, diabetes mellitus or hypertension.Complete chemistry profile was performed on serum and urine of all reminder 86 patients (46 female and 40 male. Patients classified into two groups: β-thalassemia minor with anemia and without anemia. Another control group include 50 healthy individuals also considered.Then data analyzed by proper statistical methods. Results: 20 out of 86 reminder cases e.g. 24% showed at least one index of renal tubular dysfunction.58% of patients was been anemic and 42% non anemic. The most prominent tubular dysfunction was seen in a 29 years old lady with glucosuria and without anemia. conclusion: β-Thalassemia minor is common in Iran specially in Fars province. This study revealed significant renal tubular dysfunction in patient with β-thalassemia minor. So it is necessary to check out thalassemic patients for renal function tests periodically. Key words: β-thalassemia, minor,renal tubular dysfunction

  3. Prevalence of anti-HAV antibodies in multitransfused patients with beta-thalassemia

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    Dimitrios Siagris; Chryssoula Labropoulou-Karatza; Alexandra Kouraklis-Symeonidis; Irini Konstantinidou; Myrto Christofidou; Ioannis Starakis; Alexandra Lekkou; Christos Papadimitriou; Alexandros Blikas; Nicholas Zoumbos


    AIM:To detect the prevalence of anti-HAV IgG antibodies in adult multitransfused beta-thalassemic patients.METHODS:We studied 182 adult beta-thalassemic patients and 209 controls matched for age and sex from the same geographic area,at the same time.Anti-HAV IgG antibodies,viral markers of hepatitis B virus (HBV)and hepatitis C virus (HCV) infection were evaluated.RESULTS:Anti-HAV IgG antibodies were detected more frequently in thalassemic patients(133/182;73.1%)than in healthy controls(38/209;18.2%,P<0.0005).When we retrospectively evaluated the prevalence of anti-HAV IgG antibodies in 176/182(96.7%)thalassemic patients,whose medical history was available for the previous ten years,it was found that 83(47.2%)of them were continuously anti-HAV IgG positive,16(9.1%)acquired anti-HAV IgG antibody during the previous ten years,49 (27.8%) presented anti-HAV positivity intermittently and 28 (15.9%) were anti-HAV negative continuously.CONCLUSION:Multitransfused adult beta-thalassemic patients present higher frequency of anti-HAY IgG antibodies than normal population of the same geographic area.This difference is difficult to explain,but it can be attributed to the higher vulnerability .of thalassemics to HAV infection and to passive transfer of anti-HAV antibodies by blood transfusions.

  4. Study of Serum Haptoglobin Level and its Relation to Erythropoietic Activity in Beta Thalassemia Children


    Seham M. Ragab; Safan, Manal A.; Badr, Eman A.


    Background Serum haptoglobin (Hp) is a reliable marker for hemolysis regardless the inflammatory state. Objective We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV) infection and iron load in β-thalassemia children. Methods Twenty two β-thalassemia major (TM),20 β-thalassemia intermedia (TI) children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered. Serum ferritin, Hp and transfe...

  5. Prevalence of anti HCV infection in patients with beta-thalassemia in Isfahan-Iran

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    Behrooz Ataei


    Conclusions: Our findings revealed that blood transfusion was the main risk factors for HCV infection among beta-thalassemic patients. Therefore, more blood donor screening programs and effective screening techniques are needed to prevent transmission of HCV infection among beta-thalassemic patients.

  6. Macrophages support pathological erythropoiesis in Polycythemia Vera and Beta-Thalassemia (United States)

    Ramos, Pedro; Casu, Carla; Gardenghi, Sara; Breda, Laura; Crielaard, Bart J.; Guy, Ella; Marongiu, Maria Franca; Gupta, Ritama; Levine, Ross L.; Abdel-Wahab, Omar; Ebert, Benjamin L.; Van Rooijen, Nico; Ghaffari, Saghi; Grady, Robert W.; Giardina, Patricia J.; Rivella, Stefano


    Regulation of erythropoiesis is achieved by integration of distinct signals. Among these, macrophages are emerging as erythropoietin-complementary regulators of erythroid development, particularly under stress conditions. We investigated the contribution of macrophages for physiological and pathological conditions of enhanced erythropoiesis. We utilized mouse models of induced anemia, Polycythemia vera and β-thalassemia in which macrophages were chemically depleted. Our data indicate that macrophages contribute decisively for recovery from induced anemia as well as the pathological progression of Polycythemia vera and β-thalassemia by modulating erythroid proliferation and differentiation. We validated these observations in primary human cultures, showing a critical direct impact of macrophages on proliferation and enucleation of erythroblasts from healthy individuals and Polycythemia vera or β-thalassemic patients. In summary, we identify a new mechanism that we named “Stress Erythropoiesis Macrophage-supporting Activity” (SEMA) that contributes to the pathophysiology of these disorders and will have critical scientific and therapeutic implications in the near future. PMID:23502961

  7. A prospective study on TT virus infection in transfusion-dependent patients with beta-thalassemia. (United States)

    Prati, D; Lin, Y H; De Mattei, C; Liu, J K; Farma, E; Ramaswamy, L; Zanella, A; Lee, H; Rebulla, P; Allain, J P; Sirchia, G; Chen, B


    A novel DNA virus designated TT virus (TTV) has been reported to be involved in the development of posttransfusion non-A-C hepatitis. We evaluated the frequency and natural course of TTV infection in a cohort of transfusion-dependent thalassemic patients in a 3-year follow-up study. Ninety-three serum hepatitis C virus (HCV) antibody-negative patients (median age of 8 years; range, 0 to 25) from eight centers were studied. Of them, 34 (37%) had an abnormal alanine-aminotransferase (ALT) baseline pattern, and the other 12 (13%) showed ALT flare-ups during the follow-up. TTV DNA in patient sera collected at the time of enrollment and at the end of follow-up was determined by polymerase chain reaction (PCR). In parallel, serum samples from 100 healthy blood donors were also tested. At baseline, 87 patient sera (93.5%) tested positive for the TTV DNA. Of these TTV DNA-positive patients, 84 (96.5%) remained viremic at the end of the study period. Of the 6 TTV DNA-negative patients, 3 acquired TTV infection during follow-up. However, no definite relation was observed between the results of TTV DNA determination and ALT patterns. TTV viremia was also detectable in 22% of blood donors. In conclusion, TTV infection is frequent and persistent among Italian transfusion-dependent patients. The high rate of viremia observed in healthy donors indicates that the parenteral route is not the only mode of TTV spread.

  8. Mithramycin encapsulated in polymeric micelles by microfluidic technology as novel therapeutic protocol for beta-thalassemia

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    Capretto L


    Full Text Available Lorenzo Capretto1, Stefania Mazzitelli2, Eleonora Brognara2, Ilaria Lampronti2, Dario Carugo1, Martyn Hill1, Xunli Zhang1, Roberto Gambari2, Claudio Nastruzzi31Engineering Sciences, University of Southampton, Southampton, UK; 2Department of Biochemistry and Molecular Biology, 3Department of Pharmaceutical Sciences, University of Ferrara, Ferrara, ItalyAbstract: This report shows that the DNA-binding drug, mithramycin, can be efficiently encapsulated in polymeric micelles (PM-MTH, based on Pluronic® block copolymers, by a new microfluidic approach. The effect of different production parameters has been investigated for their effect on PM-MTH characteristics. The compared analysis of PM-MTH produced by microfluidic and conventional bulk mixing procedures revealed that microfluidics provides a useful platform for the production of PM-MTH with improved controllability, reproducibility, smaller size, and polydispersity. Finally, an investigation of the effects of PM-MTH, produced by microfluidic and conventional bulk mixing procedures, on the erythroid differentiation of both human erythroleukemia and human erythroid precursor cells is reported. It is demonstrated that PM-MTH exhibited a slightly lower toxicity and more pronounced differentiative activity when compared to the free drug. In addition, PM-MTH were able to upregulate preferentially γ-globin messenger ribonucleic acid production and to increase fetal hemoglobin (HbF accumulation, the percentage of HbF-containing cells, and their HbF content without stimulating α-globin gene expression, which is responsible for the clinical symptoms of ß-thalassemia. These results represent an important first step toward a potential clinical application, since an increase in HbF could alleviate the symptoms underlying ß-thalassemia and sickle cell anemia. In conclusion, this report suggests that PM-MTH produced by microfluidic approach warrants further evaluation as a potential therapeutic protocol for ß-thalassemia.Keywords: microfluidics, lab-on-a-chip, design of experiments, erythroid differentiation, human erythroid precursor cells

  9. The molecular basis of beta-thalassemia intermedia in southern China: genotypic heterogeneity and phenotypic diversity

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    Sun Manna


    Full Text Available Abstract Background The clinical syndrome of thalassemia intermedia (TI results from the β-globin genotypes in combination with factors to produce fetal haemoglobin (HbF and/or co-inheritance of α-thalassemia. However, very little is currently known of the molecular basis of Chinese TI patients. Methods We systematically analyzed and characterized β-globin genotypes, α-thalassemia determinants, and known primary genetic modifiers linked to the production of HbF and the aggravation of α/β imbalance in 117 Chinese TI patients. Genotype-phenotype correlations were analyzed based on retrospective clinical observations. Results A total of 117 TI patients were divided into two major groups, namely heterozygous β-thalassemia (n = 20 in which 14 were characterized as having a mild TI with the Hb levels of 68-95 g/L except for five co-inherited αααanti-3.7 triplication and one carried a dominant mutation; and β-thalassemia homozygotes or compound heterozygotes for β-thalassemia and other β-globin defects in which the β+-thalassemia mutation was the most common (49/97, hemoglobin E (HbE variants was second (27/97, and deletional hereditary persistence of fetal hemoglobin (HPFH or δβ-thalassemia was third (11/97. Two novel mutations, Term CD+32(A→C and Cap+39(C→T, have been detected. Conclusions Chinese TI patients showed considerable heterogeneity, both phenotypically and genotypically. The clinical outcomes of our TI patients were mostly explained by the genotypes linked to the β- and α-globin gene cluster. However, for a group of 14 patients (13 β0/βN and 1 β+/βN with known heterozygous mutations of β-thalassemia and three with homozygous β-thalassemia (β0/β0, the existence of other causative genetic determinants is remaining to be molecularly defined.

  10. Phenotypic expression of hemoglobin A2 in beta-thalassemia trait with iron deficiency. (United States)

    Madan, N; Sikka, M; Sharma, S; Rusia, U


    Iron status was estimated in 463 heterozygous beta-thalassemics to delineate the effect of iron deficiency on the expression of hemoglobin A2 (HbA2) in these patients. One hundred and twenty-six (27.2%) patients with the trait were iron deficient. These iron-deficient patients had a significantly (p 3.5%) in all but one heterozygote investigated. Mean HbA2/cell was significantly (p < 0.05) lower in BTT patients with iron deficiency than in patients without iron deficiency. The presence of iron deficiency did not preclude the detection of BTT in this population. The effect of iron deficiency in BTT was apparent as a significant lowering of the Hb concentration and an increased prevalence of anemia. Iron therapy is warranted for BTT patients with iron-deficiency traits and would help to significantly raise their Hb concentration. The elevation of HbA2 was striking and could be used with reliability in making the diagnosis of BTT even in the presence of iron deficiency.

  11. Renal tubular dysfunction in pediatric patients with beta-thalassemia major

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    Ali Ahmadzadeh


    Full Text Available To evaluate the prevalence of renal tubular dysfunction in children with β-thalassemia (β-T major, we studied the glomerular and tubular function in 140 children with β-T major and compared them to a healthy control group at our center from May 2007 to April 2008. Fresh first morning samples were collected from each patient and analyzed for sodium, potassium, calcium (Ca, protein, uric acid (UA, creatinine (Cr, urine osmolality and urinary N-acetyl-β-D-glucosaminidase (UNAG activity. Blood samples were also collected for complete blood count, blood urea nitrogen (BUN, fasting blood sugar, serum creatinine (SCr, electrolytes, and ferritin before transfusion. Among the study patients, 72 were males, and the mean age was 11.5 (ranging 7-16 years. SCr levels were all within normal limits and all of them had normal glomerular filtration rate (GFR. The mean UNAG was 17.8 IU/L in the study patients (normal 0.15-11.5 IU/L and 3.2 IU/L in the control group (P 0.21 (P = 0.006. Nine (6.4% thalassemic patients with a mean age of 12 years had proteinuria (Upr/UCr > 0.2. Sixty-nine (49.3% out of the 140 patients and 45 (65.2% of the patients having UNAG had uricosuria also (UUA/UCr > 0.26. Ten (7% patients had microscopic hematuria and 10 (7% patients with a mean age of 13.5 years had glucosuria or diabetes mellitus. We conclude that tubular dysfunction is a relative common complication of the β-T major; UNAG and its index are the best to detect renal tubular dysfunction in these patients. Currently, periodic measurement of UCa/UCr and UUA/UCr ratios as well as urinalysis are recommended.

  12. Antioxidant status in beta thalassemia major: A single-center study

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    Faiza Waseem


    Full Text Available Background: Homozygous β thalassemia may lead to a marked reduction or absence of normal β chain production and accumulation of unpaired alpha-globin chains. A crucial component in the oxidant susceptibility of the thalassemic RBC is the release of heme and iron from the excessive, unpaired α-globin chains. This release can initiate self-amplifying redox reactions, which deplete the cellular reduction potential (e.g., GSH, oxidize additional hemoglobin and accelerate RBC destruction. Furthermore, β-thalassemia patients are under continuous blood transfusion, which, although life-saving, leads to an iron overload with a resultant increase in non-transferrin-bound iron that may cause greater tissue toxicity than iron in other forms. Iron-induced oxidative stress is known to be one of the most important factors determining cell injury in thalassemic patients. Therefore, we designed this study to obtain a comprehensive picture of the iron overload, antioxidant status and cell damage in β thalassemia major patients undergoing regular blood transfusion. Materials and Methods: A total of 48 diagnosed patients of β thalassemia major and 30 age- and sex-matched healthy subjects were included in the study. Estimation of hemoglobin, hematocrit, glutathione peroxidase (GPX, superoxide dismutase (SOD,vitamin E, serum ferritin, total and direct bilirubin, AST and ALT was carried out. Results: The levels of vitamin E, antioxidant enzymes GPX and SOD were significantly lowered in β thalassemic patients as compared with the control group (P<0.001. Serum total and direct bilirubin, AST and ALT were significantly elevated in thalassemic subjects as compared with the control group, indicating liver cell damage. Conclusion: Thus, our findings indicate that thalassemics are in a state of enhanced oxidative stress and that the administration of selective antioxidants would represent a promising approach toward counteracting oxidative damage and its deleterious effects on the disease status.

  13. Insulin-like growth factor-1 levels in children with Beta-thalassemia minor

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    Mehran Karimi


    Full Text Available Objective: Growth retardation in children with b-thalassemia major is multifactorial. Some etiologies described for this condition are hemochromatosis, disturbed growth hormone (GH / insulin growth factor-1 (IGF-1 axis, undernutrition and hypermetabolism. It has also been proven that growth retardation is present in b-thalassemia major children despite regular transfusion and chelation. Our aim was to evaluate the level of IGF-1 in b-thalassemia minor subjects and compare it with that in healthy children. Material and Methods: Fifty children aged 6 months to 15 years with b-thalassemia minor (32 males, 18 females and 50 age- and sex-matched normal healthy children were selected. Medical history was taken and complete physical examination was done in each case; IGF-1 level was checked in all cases. This study was done in Shiraz, southern Iran, during 2005.Results: IGF-1 levels were significantly lower in b-thalassemia minor children than normal children (P = 0.015. This result demonstrates that some etiologies of growth failure in b-thalassemia major other than those described to date can exist, which may be shared with b-thalassemia minor in feature or may be transformed by genes that are either expressed or not.Conclusion: We conclude that in addition to that observed in b-thalassemia major, IGF-1 level is also decreased in b-thalassemia minor, and these two may have similar etiologies.

  14. Metabolic and endocrinologic complications in beta-thalassemia major: a multicenter study in Tehran

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    Hashemi Reza


    Full Text Available Abstract Background The combination of transfusion and chelation therapy has dramatically extended the life expectancy of thalassemic patients. The main objective of this study is to determine the prevalence of prominent thalassemia complications. Methods Two hundred twenty patients entered the study. Physicians collected demographic and anthropometric data and the history of therapies as well as menstrual histories. Patients have been examined to determine their pubertal status. Serum levels of 25(OH D, calcium, phosphate, iPTH were measured. Thyroid function was assessed by T3, T4 and TSH. Zinc and copper in serum were determined by flame atomic absorption spectrophotometry. Bone mineral density (BMD measurements at lumbar and femoral regions have been done using dual x-ray absorptiometry. The dietary calcium, zinc and copper intakes were estimated by food-frequency questionnaires. Results Short stature was seen in 39.3% of our patients. Hypogonadism was seen in 22.9% of boys and 12.2% of girls. Hypoparathyroidism and primary hypothyroidism was present in 7.6% and 7.7% of the patients. About 13 % of patients had more than one endocrine complication with mean serum ferritin of 1678 ± 955 micrograms/lit. Prevalence of lumbar osteoporosis and osteopenia were 50.7% and 39.4%. Femoral osteoporosis and osteopenia were present in 10.8% and 36.9% of the patients. Lumbar BMD abnormalities were associated with duration of chelation therapy. Low serum zinc and copper was observed in 79.6% and 68% of the study population respectively. Serum zinc showed significant association with lumbar but not femoral BMD. In 37.2% of patients serum levels of 25(OH D below 23 nmol/l were detected. Conclusion High prevalence of complications among our thalassemics signifies the importance of more detailed studies along with therapeutic interventions.

  15. The Correlation between Troponin and Ferritin Serum Levels in the Patients with Major Beta-Thalassemia

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    Iraj Shahramian


    Full Text Available Background: Thalassemia is a hereditary hemoglobinopathy whose most common complication is cardiac involvement which ends up in these patients’ death. Since troponin is a sensitive and specific marker for the detection of microinfarct, we studied the relationship between troponin and ferritin serum levels for early diagnosis of cardiac involvement in these patients. Materials and Methods: This case-control study was performed on 80 patients, including 40 patients with major thalassemia and normal echocardiography and 40 healthy volunteers ranging from 6 months to 16 years old. All the children were examined and the eligible children who were not infected with known heart disease, iron deficiency anemia, kidney disease, diabetes, fever, and systemic diseases were enrolled into the study after obtaining written informed consents from their parents. At 8:00 A.M. before breakfast, 5cc blood was drawn from these children. After collecting the samples, ferritin and troponin serum levels were evaluated using ELISA and electro- kymonolonsense methods, respectively. The gathered data were analyzed through the SPSS statistical software (v. 20 and T-test. Besides, P value<0.05 was considered as statistically significant. Results: The study results revealed a significant difference between the two groups regarding the mean of the serum levels of troponin (P=0.045 and ferritin (P=0.001. In this study, no significant correlation was observed between serum troponin and ferritin levels and age and BMI in the two groups. Also, no significant relationship was found between serum troponin level and sex (P=0.264. Conclusions: In microinfarct, troponin increases independent of ferritin; therefore, it can be used for early detection of cardiac involvement in thalassemia patients to determine the sub-clinical effects.


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    Seham Ragab


    Full Text Available Background  :Serum haptoglobin (Hp is a reliable marker for hemolysis regardless the inflammatory state.  Objective: We investigated the possible relation between Hp depletion and hemolysis severity, hepatitis C virus (HCV infection and iron load in β-thalassemia children. Methods: Twenty  two β-thalassemia major (TM ,20 β-thalassemia  intermedia (TI children with 20 age and sex matched healthy controls were involved. Pre-transfusion hemoglobin level was considered . Serum ferritin , Hp  and transferrin receptor  levels (sTfR  (by ELISA , alanine aminotransferase (ALT and  aspartate aminotransferase (AST  (by colorimetric method were assayed. Markers of hepatitis C virus  (HCV  were done by PCR. Results:  The mean Hp levels among the studied groups were as follows; 8.02 ± 0.93 (mg/dl , 8.6 ±0.72 (mg/dl  and 122  ± 18.5(mg/dl   for TM ,TI and the controls respectively . Both patient groups had significantly lower Hp level compared to the controls (P<0.0001  with significant lower level in TM compared to TI  children ( P= 0.034  .Significant inverse correlations were  found between serum Hp and sTfR levels in thalassemia children combined and in each group (TM and TI as well as among HCV infected children. STfR   was the only significant independent predictor for  serum Hp level (t= -5.585 , P<0.0001 . Among  HCV infected patients , no significant correlation was found between serum Hp and serum transaminases  .Conclusion:  Serum Hp depletion in thalassemia had significant relation to disease severity and correlated   well with their erythropoietic activity, as assessed by the measurement of  sTfR without significant relation  HCV infection . Large sample  multicenter studies are  recommended.


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    Anju Barhai Teli


    Full Text Available We report here a patient from upper Assam region of India with Hb E / β thalassemia disease, whose father belongs to the tea garden community and mother is Assamese where Hb E is very common. The patient was suffering from severe anaemia and hepatosplenomegaly. After examination two units of blood transfusion and folic acid course were given to the patient. Patient was finally treated with c helation therapy

  18. Effects of Vitamin E and Zinc Supplementation on Antioxidants in Beta-Thalassemia Major Patients

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    Abbasali Keshtkar


    Full Text Available Objective:In beta thalassemic patients, tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body. This study was conducted to determine the effect of zinc and vitamin E supplementation on antioxidant status in beta-thalassemic major patients. Methods:This double blind randomized clinical trial was carried out on 120 beta thalassemic patients older than 18 years. Patients were randomly categorized in four groups. Zinc (50mg/day and vitamin E (400mg/day supplements were administered for former and latter group, respectively. In the third group both supplements were administered in similar doses. The fourth (control group received no supplement. The effect of supplementations on serum zinc and vitamin E, superoxide dismutase (SOD, glutathione peroxidase (GPX, total antioxidant capacity (TAC and body mass index (BMI were measured at the beginning and the end of the study. Findings:Serum zinc levels in group 1 and 3 were significantly increased (P<0.007 and P<0.005, respectively. Serum vitamin E levels in group 2 and 3 were also increased significantly (P<0.001. Mean GPX activity in group1, 2 and 3 decreased significantly (P<0.015, P<0.032 and P<0.029, respectively. Mean SOD activity and TAC did not show significant change after supplementation. BMI had significant increase in all treated groups (P<0.001. Conclusion:Our results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage.

  19. Effects of Vitamin E and Zinc Supplementation on Antioxidants in Beta thalassemia major Patients (United States)

    Rashidi, Mohammadreza; Aboomardani, Maryam; Rafraf, Maryam; Arefhosseini, Seyed-Rafie; Keshtkar, Abbasali; Joshaghani, Hamidreza


    Objective In beta thalassemic patients, tissue damage occurs due to oxidative stress and it happens because of the accumulation of iron in the body. This study was conducted to determine the effect of zinc and vitamin E supplementation on antioxidant status in beta-thalassemic major patients. Methods This double blind randomized clinical trial was carried out on 120 beta thalassemic patients older than 18 years. Patients were randomly categorized in four groups. Zinc (50mg/day) and vitamin E (400mg/day) supplements were administered for former and latter group, respectively. In the third group both supplements were administered in similar doses. The fourth (control) group received no supplement. The effect of supplementations on serum zinc and vitamin E, superoxide dismutase (SOD), glutathione peroxidase (GPX), total antioxidant capacity (TAC) and body mass index (BMI) were measured at the beginning and the end of the study. Findings Serum zinc levels in group 1 and 3 were significantly increased (P<0.007 and P<0.005, respectively). Serum vitamin E levels in group 2 and 3 were also increased significantly (P<0.001). Mean GPX activity in group1, 2 and 3 decreased significantly (P<0.015, P<0.032 and P<0.029, respectively). Mean SOD activity and TAC did not show significant change after supplementation. BMI had significant increase in all treated groups (P<0.001). Conclusion Our results suggest that beta thalassemic patients have enhanced oxidative stress and administration of selective antioxidants may preclude oxidative damage. PMID:23056757

  20. The Association between Myocardial Iron Load and Ventricular Repolarization Parameters in Asymptomatic Beta-Thalassemia Patients

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    Mehmet Kayrak


    Full Text Available Previous studies have demonstrated impaired ventricular repolarization in patients with β-TM. However, the effect of iron overload with cardiac T2* magnetic resonance imaging (MRI on cardiac repolarization remains unclear yet. We aimed to examine relationship between repolarization parameters and iron loading using cardiac T2* MRI in asymptomatic β-TM patients. Twenty-two β-TM patients and 22 age- and gender-matched healthy controls were enrolled to the study. From the 12-lead surface electrocardiography, regional and transmyocardial repolarization parameters were evaluated manually by two experienced cardiologists. All patients were also undergone MRI for cardiac T2* evaluation. Cardiac T2* score <20 msec was considered as iron overload status. Of the QT parameters, QT duration, corrected QT interval, and QT peak duration were significantly longer in the β-TM group compared to the healthy controls. Tp−Te and Tp−Te dispersions were also significantly prolonged in β-TM group compared to healthy controls. (Tp-Te/QT was similar between groups. There was no correlation between repolarization parameters and cardiac T2* MRI values. In conclusion, although repolarization parameters were prolonged in asymptomatic β-TM patients compared with control, we could not find any relation between ECG findings and cardiac iron load.

  1. Iron metabolism in heterozygotes for hemoglobin E (HbE), alpha-thalassemia1, or beta-thalassemia and in compound heterozygotes for HbE/ beta-thalassemia

    NARCIS (Netherlands)

    Zimmermann, M.B.; Fucharoen, S.; Winichagoon, P.; Sirankapracha, P.; Zeder, C.; Gowachirapant, S.; Judprasong, K.; Tanno, T.; Miller, J.L.; Hurrell, R.F.


    BACKGROUND: Despite large populations carrying traits for thalassemia in countries implementing universal iron fortification, there are few data on the absorption and utilization of iron in these persons. OBJECTIVE: We aimed to determine whether iron absorption or utilization (or both) in women hete

  2. Identification of low frequency anti-erythrocyte antibodies in chronically transfused patient with beta-thalassemia: a case report

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    Ana Rúbia Magalhães Ferreira


    Full Text Available The rate of erythrocyte alloimmunization in tranfusion-dependent patients can reach 50%, although the frequency of clinically relevant antibodies in transfused patients is not fully known, it is estimated that about 1% of patients are sensitized to each unit of transfused RBCs. The aim of this study is to report the case of  an 11-year-old girl with ?-thalassemia major, chronically transfused, which was detected in pre-transfusion protocol, the presence of two rare anti-erythrocyte antibodies: anti-Colton b (anti-Cob and anti-Lutheran 14 (anti-Lu14. To survey the clinical and laboratory patient history, research records filed in the archives of the university hospital in which the patient is monitored system was performed. The phenotyping erythrocyte in multitransfused patients is essential to decrease the risk of complications due to alloimmunization and estimate the availability of compatible blood. Thus, the report of this case may contribute to increase knowledge about of the real frequency of uncommon anti-erythrocyte antibodies in thalassemic patients.

  3. Hb Wilde and Hb Patagonia: two novel elongated beta-globin variants causing dominant beta-thalassemia. (United States)

    Scheps, Karen G; Hasenahuer, Marcia A; Parisi, Gustavo; Fornasari, María S; Pennesi, Sandra P; Erramouspe, Beatriz; Basack, Felisa N; Veber, Ernesto S; Aversa, Luis; Elena, Graciela; Varela, Viviana


    We describe here the molecular and hematological characteristics of novel frameshift mutations in exon 2 of the HBB gene (in heterozygous state) found in two Argentinean pediatric patients with dominant β-thalassemia-like features. In Hb Wilde, HBB:c.270_273delTGAG(p.Glu90Cysfs*67), we detected the deletion of the third base of the codon 89 (T) and the codon 90 (GAG), whereas in Hb Patagonia, HBB:c.296_297dupGT(p.Asp99Trpfs*59), the frameshift mutation was due to a duplication of a 'GT' dinucleotide after the second base of codon 98 (GTG). The Hb Patagonia and Hb Wilde mutations would result in elongated β-globin chains with modified C-terminal sequences and a total of 155 and 157 amino acids residues, respectively. Based on bioinformatics and structural analysis, as well as protein modeling, we predict that the elongated β-globins would affect the formation of the αβ dimers and their stability, which would further support the mechanism for the observed clinical features in both patients.

  4. Erythrocyte Catalase Activity in More Frequent Microcytic Hypochromic Anemia: Beta-Thalassemia Trait and Iron Deficiency Anemia

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    Sandra Stella Lazarte


    Full Text Available Most common microcytic hypochromic anemias are iron deficiency anemia (IDA and β-thalassemia trait (BTT, in which oxidative stress (OxS has an essential role. Catalase causes detoxification of H2O2 in cells, and it is an indispensable antioxidant enzyme. The study was designed to measure erythrocyte catalase activity (ECAT in patients with IDA (10 or BTT (21, to relate it with thalassemia mutation type (β0 or β+ and to compare it with normal subjects (67. Ninety-eight individuals were analyzed since September 2013 to June 2014 in Tucumán, Argentina. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA2, catalase, and iron status were performed. β-thalassemic mutations were determined by real-time PCR. Normal range for ECAT was 70,0–130,0 MU/L. ECAT was increased in 14% (3/21 of BTT subjects and decreased in 40% (4/10 of those with IDA. No significant difference (p=0,245 was shown between normal and BTT groups, while between IDA and normal groups the difference was proved to be significant (p=0,000. In β0 and β+ groups, no significant difference (p=0,359 was observed. An altered ECAT was detected in IDA and BTT. These results will help to clarify how the catalase activity works in these anemia types.

  5. Evaluation of Myocardial Performance Index(Mpi in Beta Thalassemia Major Patients at the Ali Asghar Hospital , Zahedan , Iran

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    R Sohrevardi


    Full Text Available Introduction : Patients with major thalassemia need recurrent transfusions and if not treated are at risk of heart dysfunction. Heart tissue could be abnormal in patients who use desferral continously due to iron deposits , fibrosis , hypertrophy and side effects of chronic anemia. Cardiac involvement is the main cause of morbidity and mortality in major thalassemics, so we decided to improve early diagnosis of cardiac involvement by measuring myocardial performance index( MPI . Method & Materials : This case-control study was performed from April 2003 to December 2003 at the Ali-Asghar pediatrics hospital, Zahedan, Iran. MPI of both ventricles was measured by Doppler echocardiography in 48 patients with major thalassemia aged between 10-18 years and compared with 48 age , sex-matched controls. Patients had no abnormality in physical examination , chest x-ray and ECG and echocardiography did not show heart failure. Hemoglobin and serum ferritin levels was measured in all patients before echocardiography. Results: Mean age of patients was 12.3±2.4 years and that in the control group was 12.7±2years . Right ventricle isovolumetric relaxation time (RVIRT (107 ± 14 vs 94 ±14 , p0.05 and LVICT (31 ± 13 vs 21 ± 15 , p0.05 in the two groups. Finally, RVMPI (0.59 ± 0.12 Vs 0.46 ± 0.12 , p<0.001 was increased in 87% of patients and LVMPI (0.49 ± 0.12 Vs 0.41± 0.09 , p0.05. Conclusion: This study showed that RVMPI and LVMPI increase in major thalassemia patients that indicates systolic and diastolic dysfunction and RVMPI increases more than LVMPI. On the other hand, MPI has a direct correlation with serum ferritin . On the basis of this study ,we suggest MPI measurement in serial echocardiography in asymptomatic major thalassemia patients.

  6. Evaluating the Correlation between Serum NT-proBNP Level and Diastolic Dysfunction Severity in Beta-Thalassemia Major Patients

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    Behzad Alizadeh


    Full Text Available Background: N-terminal pro-brain natriuretic peptide (NT-proBNP is a sensitive biomarker for the detection of asymptomatic left ventricular (LV dysfunction. Since β-thalassemia major patients suffer from early diastolic dysfunction due to iron deposition of chronic blood transfusion, we tried to evaluate the correlation between the serum NT-proBNP level and the severity of LV diastolic dysfunction determined by echocardiography in these patients. Methods: Fifty β-thalassemia major patients with normal LV systolic function were studied by tissue Doppler echocardiography, and blood samples were taken at the same time to measure the serum NT-proBNP level. Using flow velocity through the mitral valve on the tissue velocity of the mitral annulus in early ventricular filling (E/E' as an LV diastolic function indicator, the patients were divided into 3 groups: group 1 no diastolic dysfunction (E/E' < 8, group 2 suspected diastolic dysfunction (E/E' = 8-15, and group 3 documented diastolic dysfunction (E/E' >15. Other variables assessed included sex, age, method of chelator therapy, and mean hemoglobin and ferritin levels for the past 2 years.Results: According to the echocardiographic findings of all the 50 patients (29 male and 21 female with an age range of 11-35 years (mean = 17.98 y, 46% were classified in group 1, 54% in group 2, and none in group 3. The NT-proBNP level was 1070 ± 566 ng/mL in group 1 and 974 ± 515 ng/mL in group 2. The t-test showed no significant difference between groups 1 and 2 in the NT-proBNP level (p value = 0.536. Conclusions: Due to specific conditions in thalassemia major patients, the correlation between the serum NT-proBNP level and the severity of diastolic dysfunction seems to be not meaningful.

  7. Evaluating the Correlation between Serum NT-proBNP Level and Diastolic Dysfunction Severity in Beta-Thalassemia Major Patients (United States)

    Alizadeh, Behzad; Badiee, Zahra; Mahmoudi, Mahmoud; Mohajery, Mahsa


    Background: N-terminal pro-brain natriuretic peptide (NT-proBNP) is a sensitive biomarker for the detection of asymptomatic left ventricular (LV) dysfunction. Since β-thalassemia major patients suffer from early diastolic dysfunction due to iron deposition of chronic blood transfusion, we tried to evaluate the correlation between the serum NT-proBNP level and the severity of LV diastolic dysfunction determined by echocardiography in these patients. Methods: Fifty β-thalassemia major patients with normal LV systolic function were studied by tissue Doppler echocardiography, and blood samples were taken at the same time to measure the serum NT-proBNP level. Using flow velocity through the mitral valve on the tissue velocity of the mitral annulus in early ventricular filling (E/E') as an LV diastolic function indicator, the patients were divided into 3 groups: group 1) no diastolic dysfunction (E/E' 15). Other variables assessed included sex, age, method of chelator therapy, and mean hemoglobin and ferritin levels for the past 2 years. Results: According to the echocardiographic findings of all the 50 patients (29 male and 21 female) with an age range of 11-35 years (mean = 17.98 y), 46% were classified in group 1, 54% in group 2, and none in group 3. The NT-proBNP level was 1070 ± 566 ng/mL in group 1 and 974 ± 515 ng/mL in group 2. The t-test showed no significant difference between groups 1 and 2 in the NT-proBNP level (p value = 0.536). Conclusion: Due to specific conditions in thalassemia major patients, the correlation between the serum NT-proBNP level and the severity of diastolic dysfunction seems to be not meaningful. PMID:27928257

  8. Erythrocyte Catalase Activity in More Frequent Microcytic Hypochromic Anemia: Beta-Thalassemia Trait and Iron Deficiency Anemia (United States)

    Lazarte, Sandra Stella; Mónaco, María Eugenia; Jimenez, Cecilia Laura; Ledesma Achem, Miryam Emilse; Terán, Magdalena María; Issé, Blanca Alicia


    Most common microcytic hypochromic anemias are iron deficiency anemia (IDA) and β-thalassemia trait (BTT), in which oxidative stress (OxS) has an essential role. Catalase causes detoxification of H2O2 in cells, and it is an indispensable antioxidant enzyme. The study was designed to measure erythrocyte catalase activity (ECAT) in patients with IDA (10) or BTT (21), to relate it with thalassemia mutation type (β0 or β+) and to compare it with normal subjects (67). Ninety-eight individuals were analyzed since September 2013 to June 2014 in Tucumán, Argentina. Total blood count, hemoglobin electrophoresis at alkaline pH, HbA2, catalase, and iron status were performed. β-thalassemic mutations were determined by real-time PCR. Normal range for ECAT was 70,0–130,0 MU/L. ECAT was increased in 14% (3/21) of BTT subjects and decreased in 40% (4/10) of those with IDA. No significant difference (p = 0,245) was shown between normal and BTT groups, while between IDA and normal groups the difference was proved to be significant (p = 0,000). In β0 and β+ groups, no significant difference (p = 0,359) was observed. An altered ECAT was detected in IDA and BTT. These results will help to clarify how the catalase activity works in these anemia types. PMID:26527217

  9. Nonsense-mediated decay mechanism is a possible modifying factor of clinical outcome in nonsense cd39 beta thalassemia genotype

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    Maria Concetta Renda


    Full Text Available Nonsense-mediated mRNA decay (NMD is a surveillance system to prevent the synthesis of non-functional proteins. In β-thalassemia, NMD may have a role in clinical outcome. An example of premature translation stop codons appearing for the first time is the β-globin cd39 mutation; when homozygous, this results in a severe phenotype. The aim of this study was to determine whether the homozygous nonsense cd39 may have a milder phenotype in comparison with IVS1,nt110/cd39 genotype. Genotypes have been identified from a cohort of 568 patients affected by β-thalassemia. These genotypes were compared with those found in 577 affected fetuses detected among 2292 prenatal diagnoses. The nine most common genotypes, each with an incidence rate of 1.5% or over, and together accounting for 80% of genotype frequencies, underwent statistical analysis. Genotype prevalence was calculated within the overall group. Results are expressed as proportions with 95% confidence intervals; P≤0.05 was considered statistically significant. A binomial distribution was assumed for each group; z-tests were used to compare genotype frequencies observed in the patient group with frequencies in the affected fetus group. In the absence of selecting factors, prevalence of these two genotypes was compared between a cohort of 568 β-thalassemia patients (PTS and 577 affected fetuses (FOET detected during the same period. IVS1,nt110/cd39 was significantly more prevalent in FOET than PTS (P<0.0001, while there was no significant difference in prevalence of cd39/cd39 in FOET compared with PTS (P=0.524. These results suggest a cd39 genotype NMD mechanism may be associated with improved clinical outcomes in thalassemia major. 无义介导的mRNA 降解(NMD) 是一种预防非功能性蛋白质合成的监控系统。在β地中海贫血中,NMD可能对临床结果有影响。第一次出现的过早终止密码子(PTC)为β珠蛋白cd39突变;若为纯合子,则会导致严重的表型。本研究旨在确定与IVS1,nt110/cd39基因型相比,纯合子无义cd39能否有更轻度的表型。目前已确定568名β地中海贫血患者的基因型,并与从2292个产前诊断中检测出的577名地中海贫血胎儿的基因型相比较。对9个最常见基因型进行统计分析,每个基因型的发生率均为1.5%或以上,共占基因型频率的80%。在整个组中计算基因型分布情况,其结果以95%置信区间表示;若P≤0.05,则具有统计意义。各组均假定成一个二项分布;Z测试适用于比较患者组的基因型频率和地中海贫血胎儿的基因型频率。 若没有选择因子,则比较568名β地中海贫血患者(PTS)和同一时期所检测到的577个地中海贫血胎儿(FOET)这两组基因型的发生率。IVS1,nt110/cd39在FOET中的发生率明显高于PTS(P<0.0001),同时cd39/cd39 在FOET和PTS(P=0.524)中的发生率并没有明显不同。这些结果表明cd39基因型NMD机制可能与重型地中海贫血的临床结果相关。

  10. Community genetics and health approaches for bringing awareness in tribals for the prevention of beta-thalassemia in India

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    Ranbir S. Balgir


    Full Text Available Beta (β thalassemia syndromes are a group of hereditary disorders characterized by a genetic deficiency in the synthesis of β-globin chains. In the homozygous state, β-thalassemia (i.e., thalassemia major causes severe transfusion-dependent anemia. Inherited β-thalassemia syndromes cause high degree of hemolytic anemia, recurrent fever, clinical jaundice, frequent infections, bossing of cheek bones, growth retardation, splenomegaly, etc. and are responsible for high infant morbidity, mortality and fetal wastage in India. The victims include the infants, growing children, adolescent girls, pregnant women and a large chunk of ignorant people. In view of heavy genetic load, frequent requirement of blood transfusions, high cost of treatment and management, physical trauma, and mental and psychological harassment to the patients and their families, it has been realized that preventive community health and genetics approach is the most suitable for India. After carrier detection, prenatal diagnosis, and genetic couselling are the important options for couples at high risk for β-thalassemia. A prerequisite for successful prevention and intervention approach in India is the health education, bringing public awareness, sensitization, and community screening for the identification of heterozygotes or carriers in the concerned community. Some suggestions for the prevention of β-thalassemia in the vulnerable communities of India have been over emphasized for amelioration.β地中海贫血综合症是一簇遗传性异常,其特点是β球蛋白链接合处基因缺失。β地贫(或重型地贫)在纯和状态下导致严重的输液依赖型贫血症。遗传性的β地贫综合症引起严重的溶血性贫血、回归热、显性黄疸、常见感染、疼痛危象、颊骨浮肿、生长迟缓、脾肿大等症状,这导致在印度出现婴儿高发病率、死亡率和胎儿夭折。其受害人群包括婴儿、发育中的儿童、青春期女生、孕妇和大量无辜的人。由于该病症基因负荷重,通常需要对患者进行输血、高额治疗和护理,并对患者及其家人造成物理创伤、心理和生理困扰。印度人已认识到最适合治疗该症的方法是预防性社区卫生和基因学方法。载波检测后,β地贫高风险夫妇有必要进行产前诊断和遗传咨询。要在印度成功预防和干预该病症的蔓延,首先需要做的是:实施健康教育、提高公众意识、地贫敏感化、在相关社区进行杂合子或载波筛查以鉴定。为降低印度高发区的发病率,某些β地贫预防措施已被高度重视。

  11. [Anomalies of the masticatory apparatus in beta-thalassemia. The present status after transfusion and iron-chelating therapy]. (United States)

    Scutellari, P N; Orzincolo, C; Andraghetti, D; Gamberini, M R


    Fifty-four homozygous beta-thalassemic patients (26 men and 28 women) aged 7 to 24 years, who had been treated with high transfusion regimen (Hb levels = 9-10 g/dl) and chelation therapy (desferrioxamine, 35-50 mg/kg), underwent clinical and radiographic investigations. This study was aimed at assessing the clinical and radiographic changes in the stomatognathic system (teeth, mandible and maxilla, occlusion relationship and dental bases). All patients underwent orthopantomography and teleradiography of the skull, in the lateral view. Twenty thalassemic patients (13 men and 7 women) of the same age but treated with low transfusion regimes (Hb levels = 5-6 g/dl) were examined as a control group. Our results indicate that: 1) in the control group, osteopenia is the specific lesion of anemia, in both the alveolar process and the mandible, following marrow expansion. Consequently, diastema of incisors and several types of malocclusion follow--i.e., overjet, anterior open-bite and crossbite, nearly all of them associated with II dental and skeletal patterns of Angle's classification. 2) In adequately transfused patients, no lesions are observed in 55% of cases, in both the teeth and the facial skeleton. This means that current treatment methods can prevent bone abnormalities, especially if transfusions begin at birth. Nevertheless, osteopenia of the mandible (31.4%) and dental and/or skeletal malocclusions (40.7%) remain in many cases, because of persistent marrow expansion, which usually follows incorrect treatment. 3) General dental diseases--e.g., caries, paradentosis, gingivitis, etc.--affect both populations with the same incidence.

  12. Imaging findings in a child with calcineurin inhibitor-induced pain syndrome after bone marrow transplant for beta thalassemia major

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    Ayyala, Rama S.; Arnold, Staci D.; Bhatia, Monica; Dastgir, Jahannaz [Columbia University Medical Center, Morgan Stanley Children' s Hospital, Department of Radiology, New York, NY (United States)


    Calcineurin inhibitor-induced pain syndrome is an entity recognized in patients on immunosuppressive therapy after transplantation. Diagnosis is characterized by onset of pain beginning in the setting of an elevated calcineurin-inhibitor trough level. Reducing the medication dose relieves symptoms. Imaging findings can be nonspecific, including bone marrow edema and periosteal reaction. We present the unique case of calcineurin inhibitor-induced pain syndrome in a child and review the imaging findings. (orig.)

  13. Masked deficit of vitamin B12 in the patient with heterozygous beta-thalassemia and spastic paraparesis. (United States)

    Bilic, Ernest; Bilic, Ervina; Zagar, Marija; Juric, Stjepan


    The spinal cord, brain, optic nerves and peripheral nerves may be affected by vitamin B12 (cobalamin) deficiency. Deficiency of vitamin B12 also causes megaloblastic anaemia, meaning that the red blood cells are usually larger than normal. In this paper we report a 16-year old girl who was referred to us for the evaluation of mild paraparesis and paresthesias marked by tingling "pins and needles" feelings and general weakness. The patient, her parents and sisters were on a strict vegan diet, which made us believe that vitamin B12 deficiency may be the possible cause of the neurologic clinical manifestations. The serum level of vitamin B12 was low, but there was no macrocytosis in the routine blood examination. The electrophoresis of haemoglobin was pathologic, there was 3.7% of HbA2 and 11.6% of HbF (heterozygous form of beta-thalassaemia). When megaloblastic anaemia occurs in combination with a condition that gives rise to microcytic anaemia, many megaloblastic features may be masked. Instead of being macrocytic, the anaemia could be normocytic or even microcytic. Vitamin B12 deficiency is a diagnosis that must not be overlooked. This case report turns the light on the fact that increased MCV is a hallmark in vitamin B12 deficiency, but it is not an obligatory sign.

  14. High prevalence of alpha- and beta-thalassemia in the Kadazandusuns in East Malaysia: challenges in providing effective health care for an indigenous group. (United States)

    Tan, Jin-Ai Mary Anne; Lee, Ping-Chin; Wee, Yong-Chui; Tan, Kim-Lian; Mahali, Noor Fadzlin; George, Elizabeth; Chua, Kek-Heng


    Thalassemia can lead to severe transfusion-dependent anemia, and it is the most common genetic disorder in Malaysia. This paper aims to determine the prevalence of thalassemia in the Kadazandusuns, the largest indigenous group in Sabah, East Malaysia. α- and β-thalassemia were confirmed in 33.6% and 12.8%, of the individuals studied respectively. The high prevalence of α- and β-thalassemia in the Kadazandusuns indicates that thalassemia screening, genetic counseling, and prenatal diagnosis should be included as part of their healthcare system. This preliminary paper serves as a baseline for further investigations into the health and genetic defects of the major indigenous population in Sabah, East Malaysia.

  15. MRI of the liver and the pituitary gland in patients with {beta}-thalassemia major: Does hepatic siderosis predict pituitary iron deposition?

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    Argyropoulou, Maria I.; Efremidis, Stavros C. [Department of Radiology, Medical School, University of Ioannina, 45110 Ioannina (Greece); Kiortsis, Dimitrios N. [Laboratory of Physiology, Medical School, University of Ioannina, 45110 Ioannina (Greece)


    Our objective was to study, in thalassemic patients, if hepatic siderosis evaluated by MRI could predict the pituitary iron overload. In 36 thalassemic patients (age range 6-44 years, mean age 21.7 years) the liver/fat ratio (L/F), the pituitary/fat ratio (P/F), the liver and pituitary T2 relaxation times were evaluated, by using a multiecho spin-echo sequence. Serum ferritin levels were measured and an extensive endocrine evaluation was performed. The L/F, the P/F and pituitary T2 showed a good correlation with serum ferritin (r=-0.55, r=-0.55 and r=-0.53, respectively; p<0.01). Liver T2 did not show significant correlation with serum ferritin. The variability of L/F explained only the 10.8% of the variability of pituitary T2 and of the P/F. When ferritin was added to the model it predicted only the 26.85% and the 30.8% of the variability of pituitary T2 and of the P/F, respectively. The P/F and pituitary T2 were lower in patients with hypogonadotropic hypogonadism (group 1) compared with those without pituitary dysfunction (group 2). No significant differences of L/F were found between the two groups. Hepatic iron overload evaluated by MR is a poor predictor of pituitary siderosis. The MR studies of the pituitary gland might be necessary to evaluate the pituitary iron overload. (orig.)

  16. High Prevalence of Alpha- and Beta-Thalassemia in the Kadazandusuns in East Malaysia: Challenges in Providing Effective Health Care for an Indigenous Group

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    Jin-Ai Mary Anne Tan


    Full Text Available Thalassemia can lead to severe transfusion-dependent anemia, and it is the most common genetic disorder in Malaysia. This paper aims to determine the prevalence of thalassemia in the Kadazandusuns, the largest indigenous group in Sabah, East Malaysia. α- and β-thalassemia were confirmed in 33.6% and 12.8%, of the individuals studied respectively. The high prevalence of α- and β-thalassemia in the Kadazandusuns indicates that thalassemia screening, genetic counseling, and prenatal diagnosis should be included as part of their healthcare system. This preliminary paper serves as a baseline for further investigations into the health and genetic defects of the major indigenous population in Sabah, East Malaysia.


    NARCIS (Netherlands)



    We have characterized the structural abnormality of a new alpha chain mutant found in a Kurdish; family. The clinical and hematological investigation of eight individuals have shown that the a variant is associated with a beta degrees-thalassemia mutation (nonsense codon 39). The tryptic peptide map

  18. Co-inheritance of novel ATRX gene mutation and globin (α & β) gene mutations in transfusion dependent beta-thalassemia patients. (United States)

    Al-Nafie, Awatif N; Borgio, J Francis; AbdulAzeez, Sayed; Al-Suliman, Ahmed M; Qaw, Fuad S; Naserullah, Zaki A; Al-Jarrash, Sana; Al-Madan, Mohammed S; Al-Ali, Rudaynah A; AlKhalifah, Mohammed A; Al-Muhanna, Fahad; Steinberg, Martin H; Al-Ali, Amein K


    α-Thalassemia X-linked mental retardation syndrome is a rare inherited intellectual disability disorder due to mutations in the ATRX gene. In our previous study of the prevalence of β-thalassemia mutations in the Eastern Province of Saudi Arabia, we confirmed the widespread coinheritance of α-thalassemia mutation. Some of these subjects have a family history of mental retardation, the cause of which is unknown. Therefore, we investigated the presence or absence of mutations in the ATRX gene in these patients. Three exons of the ATRX gene and their flanking regions were directly sequenced. Only four female transfusion dependent β-thalassemia patients were found to be carriers of a novel mutation in the ATRX gene. Two of the ATRX gene mutations, c.623delA and c.848T>C were present in patients homozygous for IVS I-5(G→C) and homozygous for Cd39(C → T) β-thalassemia mutation, respectively. While the other two that were located in the intronic region (flanking regions), were present in patients homozygous for Cd39(C → T) β-thalassemia mutation. The two subjects with the mutations in the coding region had family members with mental retardation, which suggests that the novel frame shift mutation and the missense mutation at coding region of ATRX gene are involved in ATRX syndrome.

  19. 77 FR 58399 - Oncologic Drugs Advisory Committee; Notice of Meeting (United States)


    ... is for the treatment of chronic iron overload in patients with non-transfusion-dependent thalassemia syndromes (beta-thalassemia intermedia, HbE beta-thalassemia, and alpha-thalassemia) aged 10 years and...

  20. The liver in patients with [beta]-thalassemia major. Determination of iron concentration with Magnetic Resonance Imaging. Il fegato dei pazienti affetti da [beta]-talassemia major. Determinazione della concentrazione di ferro con Risonanza Magnetica

    Energy Technology Data Exchange (ETDEWEB)

    Midiri, M. (Bari, Policlinico Univ. (Italy). Ist. di Radiologia); Gallo, C.; Finazzo, M. (Palermo, Policlinico Univ. ' P. Giaccone' (Italy). Ist. di Radiologia ' Pietro Cignolini' )

    The paper investigates the clinical usefulness of liver MRI in a large multicenter study because the control of iron concentration (LIC) is crucial in thalassemia major (TM) prognosis and conflicting results have been reported in small and heterogeneous groups of patients using MRI, the only very common non-invasive procedure. One hundred and eight consecutive TM patients, selected according to a specific protocol, were included in the study. This study shows that LIC can be calculated as a function of SIR. A validation study is necessary before introducing this prediction rule in clinical practice.

  1. Detection of glycemic abnormalities in adolescents with beta thalassemia using continuous glucose monitoring and oral glucose tolerance in adolescents and young adults with β-thalassemia major: Pilot study

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    Ashraf T Soliman


    Full Text Available Background: Both insulin deficiency and resistance are reported in patients with β-thalassemia major (BTM. The use of continuous blood glucose monitoring (CGM, among the different methods for early detection of glycemic abnormalities, has not been studied thoroughly in these adolescents. Materials and Methods: To assess the oralglucose tolerance (OGT and 72-h continuous glucose concentration by the continuous glucose monitoring system (CGMS and calculate homeostatic model assessment (HOMA, and the quantitative insulin sensitivity check index (QUICKI was conducted in 16 adolescents with BTM who were receiving regular blood transfusions every 2-4 weeks and iron-chelation therapy since early childhood. Results: Sixteen adolescents with BTM (age: 19.75 ± 3 years were investigated. Using OGTT, (25% had impaired fasting blood (plasma glucose concentration (BG (>5.6 mmol/L. 2-h after the glucose load, one of them had BG = 16.2 mmol/L (diabetic and two had impaired glucose tolerance (IGT (BG > 7.8 and 11.1 mmol/L and 9 with IGT (56%. HOMA and QUICKI revealed levels 0.33 (0.36 ± 0.03, respectively, ruling out significant insulin resistance in these adolescents. There was a significant negative correlation between the β-cell function (B% on one hand and the fasting and the 2-h BG (r=−0.6, and − 0.48, P < 0.01, respectively on the other hand. Neither fasting serum insulin nor c-peptide concentrations were correlated with fasting BG or ferritin levels. The average and maximum blood glucose levels during CGM were significantly correlated with the fasting BG (r = 0.68 and 0.39, respectively, with P < 0.01 and with the BG at 2-hour after oral glucose intake (r = 0.87 and 0.86 respectively, with P < 0.001. Ferritin concentrations were correlated with the fasting BG and the 2-h blood glucose levels in the OGTT (r = 0.52, and r = 0.43, respectively, P < 0.01 as well as with the average BG recorded by CGM (r = 0.75, P < 0.01. Conclusion: CGM has proven to be superior to OGTT for the diagnosis of glycemic abnormalities in adolescents with BTM. Defective β-cell function rather than insulin resistance appeared to be the cause for these abnormalities.


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    Seham Ragab


    Full Text Available Background: Cardiac iron toxicity is the leading cause of death among  β-halassaemia major (TM  patients.  Once  heart failure becomes overt , it will be  difficult to reverse . Objectives: To investigate non overt cardiac dysfunctions  in TM patients using  pulsed wave Tissue Doppler  Imaging (TD I and its relation to the iron overload and brain natruritic peptide (BNP. Methods: Thorough  clinical , conventional echo and  pulsed  wave TDI  parameters were compared between  asymtomatic 25 β-TM  patients  and 20 age and gender matched individuals. Serum ferritin and plasma BNP  levels were assayed by  ELISA .  Results: TM patients had significant higher mitral inflow early diastolic (E wave and  non significant other conventional echo  parameters. Pulsed wave TDI revealed systolic and diastolic dysfunctions in the form of significant higher  isovolumetric contraction time (ICT , ejection time ( E T and  isovolumetric relaxation time (IRT with significantly lower  mitral annulus  early diastolic velocity E` (12.07 ±2.06 vs 15.04±2.65 ,P= 0.003  in patients compared to  controls. Plasma BNP was higher in patients compared to the controls.  Plasma BNP and serum ferritin had significant correlation with each other and with pulsed wave conventional and TDI indices of systolic and diastolic functions.  Patients with E/E` ≥ 8 had  significant higher  serum ferritin  and plasma BNP levels compared to those with E/E` ratio < 8 without difference in Hb levels .Conclusion:  Pulsed wave TDI  is an  important diagnostic tool for latent cardiac dysfunction in iron loaded TM patients and is related to iron overload and BNP .

  3. 中间型β地中海贫血家系基因分子生物学特征分析%Molecular characterization of a family with beta-thalassemia intermedia

    Institute of Scientific and Technical Information of China (English)

    荣卡彬; 黄革; 蒋文玲; 李运雄; 罗宪玲; 孟锦绣; 余细勇


    目的 分析在中国人群中发现的中间型β地中海贫血家系的分子生物学特征.方法 表型检测采用标准的血液学分析技术测量RBC参数,采用高效液相色谱方法检测Hb组分.采用反向斑点杂交技术诊断β地中海贫血基因突变,利用跨越断裂点PCR技术(gap-PCR)扩增断裂点基因序列并进行测序分析.结果 先证者Hb浓度为86 g/L,属中间型地中海贫血表型.先证者父亲呈典型的小细胞低色素改变,平均红细胞容积(MCV)为63.7 fl,平均红细胞血红蛋白量(MCH)为20.4 pg,均降低;血红蛋白A2(HbA2)增加,属地中海贫血杂合子表型.而先证者母亲、外祖母和妹妹的MCV及MCH均正常,但胎儿血红蛋白(HbF)较高,HbF分别为28.3%、21.1%及33.7%,属于胎儿血红蛋白持存综合征(HPFH)杂合子表型.进一步的基因分析表明,先证者为β441-42/HPFH-6基因型的中间型地中海贫血患儿,其父母基因型分别为β41-42/βN和HPFH-6杂合子.其外祖母和妹妹均为HPFH-6杂合子.结论 发现1例β41-42/HPFH-6中间型地中海贫血病例,可为产前诊断提供可借鉴的临床经验.%Objective To analyze a rare genotype with β-thalassemia intermadia.Methods Phenotypic analysis was performed using routine hematological tests to measure red blood cell parameters and high performance liquid chromatography (HPLC)was used to measure hemoglobin fractions.The β-globin gene mutations were conducted using reverse-dot-blot and DNA sequencing of the breakpoint region were characterized with gap-PCR.Results The proband had a trait of thalassemia intermedia with reduced hemoglobin (86 g/L).The proband's father had a trait of microcytic hypochromic with reduced mean corpuscular volume(MCV),mean corpuscular hemoglobin (MCH) (63.7 fl and 20.4 pg,respectively) and an elevated level of HbA2.He had the phenotype of heterozygosity for β-thalassemia.The preband's mother,grandmother and sister had a trait of heterezygote for hereditary persistence of fetal hemoglobin (HPFH) with elevated level of HbF,which were 28.3%,21.1% and 33.7%,respectively.After molecular characterization of the family members,the proband was identified as a patient with β-thalassemia intermedia caused by co-existence of β-thalassemia(β41-42) and HPFH-6.The father was heterozygoas for β-thaiassemia (β41-42/βN) and the mother,grandmother and sister were all heterozygons for HPFH-6.Condusions A rare β-thalassemia intermedia case resulting from compound heterezygote of β41-42 with HPFH-6 is found.This study may provide clinical experiences for antenatal diagnosis.

  4. Hb D/Talassemia beta associada à anemia crônica Hb D/ Beta thalassaemia associated with chronic anaemia

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    Paulo C. Naoum


    Full Text Available We describe a case of Hb D/Beta thalassemia associated with chronic anemia. Hematological analyses performed in a patient with chronic anemia demonstrating microcytosis and hypochromic in his erythrocytes. Specific laboratory diagnosis performed by alkaline and acid electrophoresis, and fetal determination by alkali resistance, indicated it to be Hb D associated with beta thalassemia. Analyses carried out on his family (father, mother and brother confirmed the suspected diagnosis. Hb D/Beta thalassemia is a very rare interaction in the Brazilian population, and its determination required specific laboratorial techniques and hematological analyses.

  5. 遗传性球形红细胞增多症并存β地中海贫血双重溶血性贫血的鉴别诊断%Differential diagnosis of hereditary spherocytosis associated with beta thalassemia

    Institute of Scientific and Technical Information of China (English)

    李津婴; 陈莉; 黄正霞; 方超平; 蔡斌



  6. Report and Literature Review of a Missed Diagnosed Patient with Hereditary Spherocytosis Complicated with Beta-thalassemia%遗传性球形红细胞增多症并β地中海贫血漏诊并文献复习

    Institute of Scientific and Technical Information of China (English)

    周霖; 卢田天; 蔡斌; 雷蕾; 蒋瑾瑾


    目的 探讨遗传性球形红细胞增多症并β地中海贫血的临床特点、漏诊原因及其防范措施.方法 对我院收治的遗传性球形红细胞增多症并β地中海贫血漏诊后者1例的临床资料进行回顾性分析并复习相关文献.结果 患儿4岁,面色发黄3年余,出生5个月时即诊断遗传性球形红细胞增多症,多次行输血治疗,1个月前行脾切除术治疗,16 d前皮肤始进行性苍白.经血常规及溶血试验等贫血相关检查确诊遗传性球形红细胞增多症并β地中海贫血.再次予输血治疗,血红蛋白上升至正常出院.出院后随访2.5年,一直于当地医院输血及祛铁治疗,每输血2个月左右血红蛋白便降至60 ~ 70 g/L.结论 临床上同时患有遗传性球形红细胞增多症和β地中海贫血十分罕见,结合临床表现、血常规、红细胞形态学特点及溶血试验等贫血相关检查综合、系统进行分析,可防止漏诊.

  7. 基于社区水平的珠海市大人群地中海贫血的遗传筛查和产前诊断%A community-based genetic screening of large-scale population and prenatal diagnosis for alpha and beta thalassemia in Zhuhai city of Guangdong province

    Institute of Scientific and Technical Information of China (English)

    周玉球; 徐湘民; 莫秋华; 卢金汉; 李莉艳; 梁雄; 贾世奇; 肖鸽飞; 周万军; 肖奇志


    Objective To describe a community-based model for prevention and control of severe α and β thalassemias in Zhuhai city of Guangdong province.Methods Couples for premarital medical examination or regular heahhcare examination in pregnancy were enrolled in this prospective screening program,which was supported by the two-level network composed of 6 local hospitals for testing thalassemias and follow-up for genetic counseling.A conventional heterozygote screening strategy Was used to determine α and β thalasemia traits in women and their partners according to the standard procedures of hematological phenotype analysis.Then confirmative diagnosis of α and β thalassemia was performed On those couples suspected at-risk for seven thalassemia by using the PCR-based molecular diagnostic assays. The couples at risk for severe thalassemia Were counseled and offered prenatal diagnosis and termination of pregnancy in ease of an affected fetus. Results During the period between January 1998 and December 2005, the screened records included 85522 young females and their partners for premarital screening and 10439 pregnant women for prenatal screening,with 71.38% coverage of total population recorded in this city for premarital screening.Six thousands five hundreds and sixty-three individuals in total were found to be the carriers of thalassemias,with 4312 for α thalassemia (4.5%) and 2251 for β thalassemia (2.3%),respectively.One hundred and forty-eisht couples Were diagnosed to be at-risk for thalassemias,including 103 for a thalassemia and 45 for β thalassemia, respectively.Successful prenatal diagnosis was made for 142(98 for a thalasemia and 44 for β thalassemia) out of 148 (95.9%) pregnancies at-risk for severe thalassemias.Twenty-three cases of hydrops fetalis,4 of Hb H diseases and 14 of β thal assemia were identified.All 41 pregnancies with affected fetuses were voluntarily terminated.Thus, this has led to a marked decrease of scvcrc thalassemia syndrome since the program started.Conclusion We presented the first community-based prospective screening progxam in China for control of α and β thalassemia in Zhuhai city with a population of 1.29 million through premarital or prenatal screening.This model could be used for control of thalassemias and other hemoglobinopathies in other regionsof China and also in other developing countries.%目的 阐述在广东省珠海市开展基于社区的控制重型α和β地中海贫血(简称地贫)的预防模式.方法 构建由6家医院组成的二级地贫遗传服务网络,以珠海市婚前医学或产前检查人群作为筛查对象,采用常规杂合子筛查策略,以标准的血液学分析流程进行α和β地贫特征的筛查.对所有地贫疑诊对象进行随访和遗传咨询,并采用基于PCR的分子诊断技术对高风险夫妇进行确诊.在知情同意和选择的情况下,对高风险妊娠实施产前基因诊断并通过选择性引产淘汰受累的重型地贫胎儿.结果 从1998年1月至2005年12月,共筛查了85522例拟婚育龄青年和10439例孕妇,婚检地贫筛查覆盖率达到71.38%.在6563例地贫筛查阳性的病例中,α和β地贫分别为4312例(4.5%)和2251例(2.3%);总计发现148对有生育重型地贫儿可能的高风险夫妇(α地贫103对,β地贫45对),其中有142对(95.9%)高风险夫妇进行了产前诊断(α地贫98例,β地贫44例).本项目启动后共减少了41例重型地贫患儿的出生,其中包括Hb Barts水肿胎23例、Hb H病4例和重型β-地贫14例.结论 这是我国首次基于社区水平的、在拥有129万人口的珠海市实施的前瞻性α和β地贫预防监控计划.这一预防模式对我国其他地贫高发区和其他发展中国家开展地贫和其他血红蛋白病的预防有着重要的借鉴意义.

  8. Amplificação gênica alelo-específica na caracterização das hemoglobinas S, C e D e as interações entre elas e talassemias beta Allele-specific genic amplification in the characterization of hemoglobins S, C, D and interactions among them and with beta thalassemia

    Directory of Open Access Journals (Sweden)

    Luciane Cristina Bertholo


    Full Text Available INTRODUÇÃO: As hemoglobinopatias resultam de alterações hereditárias, sendo prevalentes em muitas regiões do mundo, mas atingem a população brasileira de forma significativa. Elas são decorrentes de alterações em genes estruturais responsáveis pelo aparecimento das hemoglobinas variantes e/ou em genes reguladores, resultando nas talassemias. A identificação dessas patologias tem sido rotineiramente realizada por procedimentos eletroforéticos, contudo nossa experiência laboratorial evidencia que as mesmas nem sempre apresentam resoluções suficientes para a correta caracterização da mutação. CASUÍSTICAS E MÉTODOS: O propósito deste trabalho foi estabelecer uma metodologia válida para a caracterização das hemoglobinas S, C e D em homozigose ou heterozigose, e suas possíveis interações, baseada na amplificação gênica alelo-específica (PCR-AE com a utilização de primers sense, antisense e primers que se acoplam na posição do alelo mutante e na respectiva posição do alelo normal. RESULTADOS E DISCUSSÃO: Os resultados evidenciaram a validade dessa metodologia na caracterização das mutações, sendo esse procedimento de fácil realização, reprodutível e possível de ser aplicado em um significativo número de amostras.BRACKGROUND: The hemoglobinopathies are a group of hereditary hemoglobin disorders in worldwide distribution, affecting Brazilian population significantly; they are decurrent of alterations in structural genes, responsible for hemoglobin variants, and/or in regulatory genes, resulting the thalassemia. These disorders have been identified in most cases by electrophoretics procedures, and our laboratory experience points out that sometimes they do not obtain enough resolution for a right characterization of mutation. MATERIAL AND METHOD: The objective of this study was to establish a valid laboratory methodology for the characterization of hemoglobins S, C and D in homozygous or heterozygous and possible interactions, based on the allele-specific genic amplification (PCR-AE with the use in parallel two primers that differ at their 3’ extremities and are complementary to the normal or mutated sequences. RESULTS AND DISCUSSION: The results make evident the validation of this methodology in the characterization of these mutations, once this procedure is easy to execute,to reproduce, as well as it is possible to be applied to a significative number of samples.

  9. Marcadores eletrocardiográficos para detecção precoce de doença cardíaca em pacientes com talassemia beta maior Electrocardiographic markers for the early detection of cardiac disease in patients with beta-thalassemia major

    Directory of Open Access Journals (Sweden)

    Kemal Nisli


    Full Text Available OBJETIVO: Analisar comparativamente a dispersão da onda P (DOP em pacientes com talassemia beta maior (β-TM e indivíduos saudáveis (controles para a detecção precoce do risco de arritmias. MÉTODOS: Oitenta e uma crianças com β-TM, com idades entre 4 e 19 anos, e 74 crianças saudáveis (grupo controle foram submetidas a exame eletrocardiográfico e ecocardiograma transtorácico de rotina para avaliação cardíaca. A DOP foi calculada como a diferença entre as durações máxima e mínima da onda P. RESULTADOS: Houve uma diferença estatisticamente significativa entre o grupo de estudo e o grupo controle no pico de velocidade do fluxo transmitral no início da diástole (E e na razão E/fluxo transmitral tardio (A. A duração máxima da onda P e a DOP foram significativamente maiores nos pacientes com β-TM do que nos indivíduos controles. CONCLUSÕES: O aumento da DOP em nossos pacientes com β-TM pode estar relacionado à depressão na condução intra-atrial, devido à dilatação atrial, e ao aumento da atividade simpática. Estes pacientes devem ser acompanhados atentamente devido à possibilidade de ocorrência de arritmias com risco de vida.OBJECTIVE: To comparatively evaluate P-wave dispersion (PWD in patients with β-thalassemia major (TM and healthy control subjects for the early prediction of arrhythmia risk. METHODS: Eighty-one children with β-TM, aged 4-19 years, and 74 healthy children (control group underwent routine electrocardiography and transthoracic echocardiography for cardiac evaluation. PWD was calculated as the difference between the maximum and the minimum P-wave duration. RESULTS: There was a statistically significant difference between study and control groups in peak early (E mitral inflow velocity and E/late (A velocity ratio. Maximum P-wave duration and PWD were found to be significantly higher in β-TM patients than in control subjects. CONCLUSIONS: Increased PWD in our β-TM patients might be related to depression of intra-atrial conduction due to atrial dilatation and increased sympathetic activity. These patients should be closely followed up for risk of life-threatening arrhythmias.

  10. 广西重型β地中海贫血HBS1L-MYB基因多态性与胎儿血红蛋白的相关性研究%Correlation between HBS1L-MYB polymorphism and fetal hemoglobin in beta-thalassemia major in Guangxi

    Institute of Scientific and Technical Information of China (English)

    于春蓝; 刘容容; 赖永榕


    Objective To study the correlation between single nucleotide polymorphism of HBS1L-MYB genes ( rs35959442, rs4895441,rs9399137) and fetal hemoglobin(HbF) in patients with β-thalassemia major.Methods Single nucleotide polymorphisms of HBS1L-MYB genes ( rs35959442, rs4895441, rs9399137 ) were determined by polymerase chain reaction-restriction fragment length polymorphism(PCR-RELP) and DNA sequencing among 64 β-thalassemia major patients(case group) and 64 normal individuals(control group).Their association with HbF level was analyzed.Results The G allele frequencies of rs4895441 and rs35959442 loci of HBS1L-MYB gene in the case group were significantly higher than those in the control group(P0.05).rs4895441 and rs35959442 loci positively correlated with HbF level (P0.0167).Conclusion HBS1L-MYB polymorphism correlates with HbF level in patients withβ-thalassemia major in Guangxi.The rs4895441 and rs35959442 mutations might contribute to increasing the HbF level.%目的:研究HBS1L-MYB基因rs35959442、rs4895441和rs9399137位点多态性与胎儿血红蛋白( HbF)的相关性。方法通过聚合酶链反应-限制性片段长度多态性,DNA测序技术检测广西籍64例重型β地中海贫血患者(病例组)及64例健康对照组HBS1L-MYB基因rs35959442、rs4895441和rs9399137位点多态性,并分析它们与HbF水平的相关性。结果病例组HBS1L-MYB基因rs4895441和rs35959442位点G等位基因频率均明显高于健康对照组(P<0.05),而两组rs9399137位点等位基因频率及基因型分布比较,差异无统计学意义(P>0.05)。 rs4895441位点、rs35959442位点与HbF水平呈正相关关系(P<0.0167),rs9399137位点与HbF无相关关系(P>0.0167)。结论广西重型地中海贫血HBS1L-MYB基因多态性与HbF水平有关,rs35959442和rs4895441位点基因突变可能有助于提高HbF的水平。

  11. 重型β地中海贫血患者BCL11A表达水平及其与临床表现的相关性分析%Expression of BCL11 A in Patients with Beta Thalassemia Major and Its Correlation with Clinic Manifestation

    Institute of Scientific and Technical Information of China (English)

    尹晓林; 林万华; 方素萍; 陈希玲; 张天郎; 罗瑞贵; 李静; 吴志奎; 张新华


    目的 探讨重型β地中海贫血患者( thalassemia major,TM)BCL11A表达特点及其与临床表现的关系.方法 正常人和TM患者各24例,分离外周血单个核细胞,实时荧光定量聚合酶链反应(quantitative real time polymerase chain reaction,qRT-PCR)法检测BCL11A、γ基因mRNA表达水平,同时检测血常规血红蛋白(hemoglobin,Hb)、血红蛋白分析仪检测胎儿血红蛋白(fetal hemoglobin,HbF),并行相关性检验.结果 TM患者的HbF、γmRNA水平显著高于正常人群(13.7%±13.6% vs 0.28%±0.15%,P<0.001;2479%±279% vs 10.61%±0.41%,P<0.001),2组BCL11A基因mRNA水平无统计学差异(0.73%±0.26% vs 0.77%±0.22%,P=0.590).TM患者中25%(6例)的患者HbF正常,与HbF升高者比较,其γmRNA水平要低(62.10%±16.49%vs 3285.2%±2792.2%,P<0.001),但BCL11A mRNA水平无统计学差异(0.78%±0.21% vs 0.72%±(0.28%,P=0.704).TM患者BCL11A mRNA水平与首次输血年龄无显著相关(r=0.201,P=0.345).结论 BCL11A不参与TM患者的γ基因的开放和HbF代偿性增加.%Objective To investigate the expression of BCL11A in patients with thalassemia major (TM) and its correlation with clinic manifestation. Methods Peripheral blood mononuclear cells were separated from 24 TM patients and 24 normal persons, BCL11A and γ mRNA expression was determined by quantitative real time polymerase chain reaction (qRT-PCR). Hemoglobin level and HbF percentage were detected by blood routine analysis and hemoglobin analysis. Results Compared with normal control, HbF level and y mRNA level in TM patients were increased significantly (HbF; 13. 7% ± 13.6% vs0.28%±0. 15%.P<0.001, y mRNA:2479% ± 279% vs 10.61% ± 0. 41 %, P<0.001). BCLllA mRNA level was not significantly different between two groups (0. 73% ± 0. 26% us (). 77% ± 0. 22%, P = 0. 590). Six TM patients (25%) had normal HbF levels. Compared with patients having increased HbF levels, patients with normal HbF levels had lower y mRNA levels(62. 10% ± 16.49% vs 3285. 2% ± 2792. 2%, P<0.001), and similar BCLllA mRNA levels (0. 78% ± 0. 21 % vs 0. 72% ± 0. 28%, P = 0. 704). BCL11A mRNA did not correlate with the ages of first blood transfusion (r-0.201, P = 0. 345). Conclusion BCLllA does not take part in y gene upregulation and the compensatory increasing of HbF in TM patients.

  12. 毛细管电泳法在β地中海贫血患者 HbA1c和 HbA2检测中的应用%The application of capillary electrophoresis in HbA1c and HbA2 detection in beta thalassemia patients

    Institute of Scientific and Technical Information of China (English)

    徐安平; 夏勇; 纪玲; 喻晶; 周宇; 李璐


    目的探讨β地中海贫血对毛细管电泳法等8种糖化血红蛋白检测系统的影响,以及毛细管电泳糖化血红蛋白系统检测β地中海贫血中HbA2的应用。方法收集2014年1至8月北京大学深圳医院确诊的非β地中海贫血的样本338例,其中正常样本258名,α地中海贫血80例(基因型为--SEA/αα);以及β地中海贫血且不合并其他血红蛋白病样本(α珠蛋白基因正常,β珠蛋白基因异常且为杂合子)225例。采用毛细管电泳法( Capillary 2 Flex Piercing)、酶法( Norudia N HbA1c )、免疫透射比浊法( one HbA1c FS)、化学发光免疫法( ARCHITECT HbA1c Reagent Kit)、亲和层析高压液相色谱法(Ultra2)和离子交换高压液相色谱法(HA8160、Variant ⅡTurbo和Variant ⅡTurbo 2.0),对正常和β地中海贫血各76例样本进行HbA1c检测,比较不同检测系统HbA1c结果的相关性。毛细管电泳糖化血红蛋白检测仪和毛细管电泳血红蛋白检测仪分别检测338例非β地中海贫血样本和225例β地中海贫血样本的HbA2,通过ROC曲线计算毛细管电泳糖化血红蛋白检测仪HbA2,建立筛查β地中海贫血的截断值。结果对于正常样本,7种检测系统与参比系统( Ultra2)的相关性良好,相关系数都>0.98;对于β地中海贫血样本,除Variant ⅡTurbo与参比系统相关系数为0.972外,其余检测系统相关系数都>0.98。除Variant ⅡTurbo外,正常样本和β地中海贫血样本HbA1c结果的偏倚差异无统计学意义。毛细管电泳糖化血红蛋白检测系统和毛细管电泳血红蛋白检测系统的HbA2有良好的相关性,相关系数为0.993。毛细管电泳糖化血红蛋白检测系统HbA2筛查β地中海贫血的截断值设定为3.38时,敏感性为98.2%,特异性为100%。结论除Variant ⅡTurbo外,β地中海贫血对于其他糖化血红蛋白检测系统无明显影响。毛细管电泳糖化血红蛋白检测系统在检测糖化血红蛋白的同时,具有筛查β地中海贫血的功能。(中华检验医学杂志,2015,38:329-332)%Objective To investigate effects of β-thalassemia on 8 HbA1c measurement systems including Capillary electrophoresis and application of HbA2 values of samples with β-thalassemia from Capillary 2 Flex Piercing HbA1c measurement systems.Methods 338 samples without β-thalassemia ( include 80 α-thalassemia with --SEA/ααgenotype) and 225 samples with β-thalassemia were collected in Peking University Shenzhen hospital from January 2014 to August 2014.Samples withβ-thalassemia are all heterozygotes with normal α-globin and abnormal β-globin, and without combining other haemoglobinopathies.76 normal samples and 76 samples with β-thalassemia were selected from above all samples, HbA1c values of which were given by capillary electrophoresis ( Capillary Flex 2 Piercing), enzymatic ( Norudia N HbA1c ), immune transmission turbidity ( oneHbA1c FS ), chemiluminescent immunoassay (ARCHITECT HbA1c Reagent Kit), boronate affinity HPLC (Trinity Ultra2)and ion exchange HPLC (HA8160, VariantⅡTurbo and Variant Ⅱ BioRad 2.0), respectively.HbA1c values given by the eight systems were compared.338 samples without β-thalassemia and 225 samples with β-thalassemia were measured by using Capillarys 2 Flex Piercing HbA1c system and capillary electrophoresis hemoglobin system, the cut-off values of HbA2 from Capillary 2 Flex Piercing HbA1c measurement system for β-thalassemia was assessed by using ROC curve.Data statistics were done by using SPSS 19.0.Results The HbA1c values of normal samples were well correlated with the comparative system.The correlation coefficients for the 7 systems are all greater than 0.98.For samples withβ-thalassemia, the correlation coefficients are all greater than 0.98 except for Variant Ⅱ Turbo.The bias between normal samples and samples with β-thalassemia have no significant difference except for VariantⅡTurbo.HbA2 values from Capillary 2 Flex Piercing

  13. What Causes Thalassemias? (United States)

    ... percent chance of inheriting two normal genes (no anemia), a 50 percent chance of inheriting one altered gene and one normal gene (beta thalassemia ... INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA NO FEAR ACT OIG ...

  14. beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, Anne; Main, Katharina Maria; Scheibel, Elma


    INTRODUCTION: Beta-thalassemia major occurs with increasing frequency among Danish children as a result of immigration. The aim of the study was to estimate the occurrence of beta-thalassemia major in Denmark, analyse the treatment and organ functions, and identify areas for an improved treatment...... strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters...... were performed. RESULTS: Twenty-six children had beta-thalassemia major. Out of these, 20 received blood transfusions, and 17 patients were chelated. Eight patients were not chelated owing to previous bone marrow transplantation, treatment with hydroxyurea or ferritin

  15. Blood Transfusion (For Parents) (United States)

    ... or bleeding disorder , such as sickle cell disease , thalassemia, or anemia caused by kidney disease , hemophilia , or ... Kids For Parents MORE ON THIS TOPIC Beta Thalassemia Sickle Cell Disease Alpha Thalassemia von Willebrand Disease ...

  16. About Thalassemia (United States)

    ... I want more information about the Foundation About Thalassemia A Basic Description | Alpha Thalassemia | Beta Thalassemia | Other ... Thalassemia | Downloadable Brochures on Thalassemia and its complications Thalassemia: A Basic Description Thalassemia is the name of ...

  17. Phase I/II Pilot Study of Mixed Chimerism to Treat Hemoglobinopathies (United States)


    Anemia, Sickle Cell; Complex and Transfusion-dependent Hemoglobinopathies; Thalassemia; Diamond-Blackfan Anemia; Bone Marrow Failure Syndromes Characterized by Severe Chronic Anemia; Alpha-Thalassemia; Beta-Thalassemia

  18. Hematopoietic Stem Cell Transplant for High Risk Hemoglobinopathies (United States)


    Sickle Cell Disease; Transfusion Dependent Alpha- or Beta- Thalassemia; Diamond Blackfan Anemia; Paroxysmal Nocturnal Hemoglobinuria; Glanzmann Thrombasthenia; Severe Congenital Neutropenia; Shwachman-Diamond Syndrome; Non-Malignant Hematologic Disorders

  19. Study of ocular manifestations in children of thalassemia


    Dhara K. Gosai; K. M. Mehariya; Jigarkumar B. Gosai


    Background: Purpose of current study was to study the ocular manifestations in beta-thalassemia major patients and assess the ocular side-effects of iron chelating agents. Methods: Cross sectional study included 45 beta Thalassemia major patients from age group of 6months to 12 years were taken. Full medical history, thorough physical examinations were done to all patients groups, and ophthalmological examination to determine the prevalence of ocular manifestations for all patient groups a...

  20. Premature epiphyseal fusion and extramedullary hematopoiesis in thalassemia

    Energy Technology Data Exchange (ETDEWEB)

    Colavita, N.; Orazi, C.; Danza, S.M.; Falappa, P.G.; Fabbri, R.


    The main skeletal abnormalities in ..beta..-thalassemia are widening of medullary spaces, rarefaction of bone trabeculae, thinning of cortical bone, and perpendicular periosteal spiculation. Premature epiphyseal fusion (PEF) and extramedullary hematopoiesis (EH) are found, though more rarely. The incidence of PEF and EH in 64 patients affected by ..beta..-thalassemia is reported. The different incidence of such complications in thalassemia major and intermedia is reported, and a possible correlation with transfusion regimen is also considered.

  1. Hematological differences between patients with different subtypes of sickle cell disease on hydroxyurea treatment

    Directory of Open Access Journals (Sweden)

    Fabia Neves


    Full Text Available OBJECTIVE: Sickle cell anemia and the interaction S/Beta thalassemia differ in hematological values due to microcytosis and hypochromia caused by the thalassemic mutation. The clinical benefit of long-term hydroxyurea treatment is undeniable in sickle cell disease with monitoring of the biological action of the drug being by the complete blood count. The objective of this work is to compare changes in some of the erythrocytic indexes between S/Beta thalassemia and sickle cell anemia patients on long-term hydroxyurea treatment. METHODS: The values of erythrocyte indexes (mean corpuscular volume and mean corpuscular hemoglobin were compared in a retrospective study of two groups of patients (Sickle cell anemia and S/Beta thalassemia on hydroxyurea treatment over a mean of six years. RESULTS: The quantitative values of the two parameters differed between the groups. Increases in mean corpuscular volume and reductions in mean corpuscular hemoglobin delay longer in S/Beta thalassemia patients (p-value = 0.018. CONCLUSION: Hematological changes are some of the beneficial effects of hydroxyurea in sickle cell disease as cellular hydration increases and the hemoglobin S concentration is reduced. The complete blood count is the best test to monitor changes, but the interpretation of the results in S/Beta thalassemia should be different.

  2. Evaluation of hemoglobinopathy screening results of a six year period in Turkey '

    Directory of Open Access Journals (Sweden)

    Seçil Gunher Arıca


    Full Text Available Background and Objectives: Hemoglobinopathies are autosomal recessive inherited diseases more commonly seen in Mediterranean countries. Hereditary blood diseases including B-thalassemia and sickle cell anemia are important health problems. In our study we aimed to analyze the results of the premarital hemoglobinopathy screening test for a 6 years period in Hatay region. Material and Methods: The study sample comprised the couples attending to the Mother and Child Health Care Center in Hatay for premarital hemoglobinopathy screening from 2004 to 2009. Hemoglobin chain analyses of 87.830 couples were evaluated. RESULTS: 175.660 people were screened at total. The prevalence of beta thalassemia trait, sickle cell anemia trait, sickle cell anemia, beta thalassemia major, beta-thalassemia intermedia, alpha-thalassemia, alpha-thalassemia trait was found as 13.921 (7,9%, 6.074 (3,4%, 631 (0.35%, 132 (0.07%, 118 (0.06%, 9 (0.005%, 150 (0.08% respectively. 72 newborns with beta-thalassemia were diagnosed as a result of the marriage of the carrier couples in 6 years. Conclusions: Hatay is a high risk region for beta-thalassemia and sickle cell anemia trait. In countries with high prevalence of hemoglobinopathies, a premarital screening program and counseling is needed to decrease the prevalence.

  3. [Prevention of mediterranean anemia in Latium: Ida Bianco archives]. (United States)

    Falchetti, Mario; Lupi, Ramona; Ottini, Laura


    Mediterranean anemia or beta-thalassemia is a hereditary syndrome characterized by a severe defect in haemoglobin production and an altered morphology of red blood cells. Homozygous condition for beta-thalassemia is characterized by short survival. Heterozygous condition is clinically found in adolescence and is characterized by a less aggressive phenotype. Ida Bianco, with her husband Ezio Silvestroni, has conducted a long struggle for beta-thalassemia prevention in Italy. They were the first to draw up an accurate map of the distribution of thalassemia in Italy and to conceive and implement a campaign against this genetic disease by the development of annual screening on at-school teenagers and pre-marriage prevention. Here we focused on the analysis of Ida Bianco's archives concerning screenings conducted on middle-schools in the Latium by the "Centro Studi della Microcitemia" of Rome from 1975 up to today. The results of the thirty-years prevention work in the Latium will be described.

  4. Prenatal diagnosis of thalassemia and hemoglobinopathies in Thailand: experience from 100 pregnancies. (United States)

    Fucharoen, S; Winichagoon, P; Thonglairoam, V; Siriboon, W; Siritanaratkul, N; Kanokpongsakdi, S; Vantanasiri, C


    In this review, we describe a simple strategy to detect the three severe thalassemic diseases commonly found in Thailand. Hb Bart's hydrops fetalis can be detected unambiguously by ultrasonography at 18-20 weeks of gestation or detected early in the first trimester by the gene amplification technique. Prenatal diagnosis for homozygous beta-thalassemia is better performed in the second trimester by in vitro protein synthesis. This is because the molecular defects of some beta-thalassemias are still unknown and homozygosity of the same mutation is low. In contrast, beta-thalassemia/Hb E is easily detected, in the first trimester, by direct visualization on electrophoresis or by dot blot analysis of enzymatically amplified DNA with a set of nonradioactively labeled oligonucleotide probes complementary to the most common mutations. We also found that the beta/gamma synthesis ratio in homozygous Hb E is similar to that of beta-thalassemia/Hb E and DNA analysis is the only method to distinguish these two conditions in the couple at risk of having either beta-thalassemia/Hb E or asymptomatic homozygous Hb E. In 100 pregnancies studied, the diagnoses were achieved in 96 pregnancies. Complications leading to fetal loss were found in 3 pregnancies: one woman developed amnionitis after fetal blood sampling; one had amniotic fluid leakage after the biopsy, and the third, carrying a normal fetus, aborted 10 days after fetal blood sampling with urinary tract infection and high fever. However, these figures are compatible with other reports and the risks are significantly lower than that of thalassemic disease the fetus is facing. One case of beta-thalassemia/Hb E was incorrectly diagnosed prenatally as being Hb E trait. In twenty-five pregnancies (25%) prenatally diagnosed to carry affected fetuses it was decided to have abortion. This study shows the feasibility of prenatal diagnosis for thalassemic diseases in Thailand which, in addition to screening and genetic counseling

  5. Types of thalassemia among patients attending a large university clinic in Kuala Lumpur, Malaysia. (United States)

    George, E; Li, H J; Fei, Y J; Reese, A L; Baysal, E; Cepreganova, B; Wilson, J B; Gu, L H; Nechtman, J F; Stoming, T A


    We have identified the beta-thalassemia mutations in 59 patients with thalassemia major and 47 patients with Hb E-beta-thalassemia, and the deletional and nondeletional alpha-thalassemia determinants in 23 out of 24 patients with Hb H disease. All persons were attending the Haematology Clinic at the National University of Malaysia in Kuala Lumpur (Malaysia). Most patients (76) were of Malay descent, while 52 patients were Chinese, and two came from elsewhere. The most frequently occurring beta-thalassemia alleles among the Malay patients were IVS-I-5 (G----C) and G----A at codon 26 (Hb E), while a few others were present at lower frequencies. The Chinese patients carried the mutation characteristic for Chinese [mainly codons 41/42 (-TTCT) and IVS-II-654 (C----T)]; Malay mutations were not observed among Chinese and Chinese mutations were virtually absent in the Malay patients. The large group of patients with Hb E-beta-thalassemia and different beta-thalassemia alleles offered the opportunity of comparing hematological data; information obtained for patients with Hb E-beta-thalassemia living in other countries was included in this comparison. Twenty-three patients with Hb H disease carried the Southeast Asian (SEA) alpha-thalassemia-1 deletion; 13 had the alpha CS alpha (Constant Spring) nondeletional alpha-thalassemia-2 determinant, while the deletional alpha-thalassemia-2 (-3.7 or -4.2 kb) was present in 10 subjects. The --/alpha CS alpha condition appeared to be the most severe with higher Hb H values. Both deletional and nondeletional types of alpha-thalassemia-2 were seen among Malay and Chinese patients.

  6. MRI features of epidural extramedullary hematopoiesis

    Energy Technology Data Exchange (ETDEWEB)

    Alorainy, Ibrahim A. E-mail:; Al-Asmi, Abdullah R.; Carpio, Raquel del


    A case of {beta}-thalassemia intermedia with spinal cord compression due to extramedullary hematopoiesis, which was successfully treated by blood transfusion, is presented. Emphasis was made on the MRI appearance of extramedullary hematopoiesis on different pulse sequences. The theories that aimed to explain the involvement of the epidural space by extramedullary hematopoiesis are discussed.

  7. The entire β-globin gene cluster is deleted in a form of τδβ-thalassemia.

    NARCIS (Netherlands)

    E.R. Fearon; H.H.Jr. Kazazian; P.G. Waber (Pamela); J.I. Lee (Joseph); S.E. Antonarakis; S.H. Orkin (Stuart); E.F. Vanin; P.S. Henthorn; F.G. Grosveld (Frank); A.F. Scott; G.R. Buchanan


    textabstractWe have used restriction endonuclease mapping to study a deletion involving the beta-globin gene cluster in a Mexican-American family with gamma delta beta-thalassemia. Analysis of DNA polymorphisms demonstrated deletion of the beta-globin gene from the affected chromosome. Using a DNA f

  8. Targeted correction of a thalassemia-associated beta-globin mutation induced by pseudo-complementary peptide nucleic acids

    DEFF Research Database (Denmark)

    Lonkar, Pallavi; Kim, Ki-Hyun; Kuan, Jean Y


    Beta-thalassemia is a genetic disorder caused by mutations in the beta-globin gene. Triplex-forming oligonucleotides and triplex-forming peptide nucleic acids (PNAs) have been shown to stimulate recombination in mammalian cells via site-specific binding and creation of altered helical structures...


    NARCIS (Netherlands)



    We evaluated the use of an HPLC method for screening hemoglobins in cord blood. We studied the genotype frequencies of the structural hemoglobin variants HbS and HbC and the synthesis variants alpha- and beta+-thalassemia in babies born on Curacao. During three months, 67.2% of all (748) newborns we

  10. Generation of a high-titer retroviral vector capable of expressing high levels of the human β-globin gene

    NARCIS (Netherlands)

    M. Sadelain (Michel); C.H.J. Wang (Jason); M. Antoniou (Michael); F.G. Grosveld (Frank); R.C. Mulligan


    textabstractRetrovirus-mediated gene transfer into hematopoietic cells may provide a means of treating both inherited and acquired diseases involving hematopoietic cells. Implementation of this approach for disorders resulting from mutations affecting the beta-globin gene (e.g., beta-thalassemia and

  11. Investigation of molecular heterogeneity of β-thalassemia disorder in District Charsadda of Pakistan (United States)

    Shakeel, Muhammad; Arif, Muhammad; Rehman, Shoaib Ur; Yaseen, Tabassum


    Objective: Thalassemia is blood related disease which arises from the reduced level of hemoglobin in red blood cells (RBC), a protein responsible for carrying oxygen inside the body. Considering its widespread occurrence in developing countries like Pakistan, this study aims to investigate the common molecular anomalies of the beta thalassemia disease in district Charsadda, Khyber Pakhtunkhwa. Methods: This work was done at Abdul Wali Khan University (AWKU) Mardan, Khyber Pakhtunkhwa, Pakistan. The work was performed on the blood samples collected from the patients and their families with beta thalassemia major (n = 13 families) belonged to District Charsadda. The collected blood samples were analyzed for presence of six known mutations with the help of polymerase cha in reaction technique i.e. amplification of refractory mutation system. Results: Our Study reports six known mutations (IVS-1-5, FSC 8/9, CD 41/42, IVS-1-1, CD 15 and FSC-5) accounting for about 90% of total beta thalassemia genes in this country. Among the reported mutations, IVS 1-5 was the most prevalent beta thalassemia gene in patients belonging to District Charsadda. Conclusion: The results and findings of the current study may help in accessing the frequency of these common mutations and in initiating pre-natal diagnosis programme in Pakistan. PMID:27182268

  12. Evaluation of β-globin gene therapy constructs in single-copy transgenic mice.

    NARCIS (Netherlands)

    J. Ellis (James); K.C. Tan-Un; P. Pasceri; A. Harper; X. Wu; P.J. Fraser (Peter); F.G. Grosveld (Frank)


    textabstractEffective gene therapy constructs based on retrovirus or adeno-associated virus vectors will require regulatory elements that direct expression of genes transduced at single copy. Most beta-globin constructs designed for therapy of beta-thalassemias are regulated by the 5'HS2 component o

  13. A mutation of the beta-globin gene initiation codon, ATG-->AAG, found in a French Caucasian man. (United States)

    Lacan, Philippe; Aubry, Martine; Couprie, Nicole; Francina, Alain


    A new mutation of the beta-globin gene initiation codon, ATG-->AAG (Met-->Tyr), is reported in a man originating from the southeast of France. Typical hematological findings of beta-thalassemia (thal) trait were found. We emphasize the importance of characterizing uncommon beta-thal mutations for genetic counseling.

  14. Molecular characterization of sickle cell anemia in the Northern Brazilian state of Pará. (United States)

    De Lemos Cardoso, Greice; Guerreiro, João Farias


    To assess alpha+-thalassemia deletion alleles, beta-thalassemia mutations and haplotypes linked to the HBB*S cluster in a sample of 130 unrelated sickle cell anemia (SCA) patients (55% female) from Belém, Pará State, for their possible effects on the patients' survival. -alpha(3.7), -alpha(42), -alpha(20.5), and -(MED) alpha+-thalassemia deletion alleles were investigated using multiplex gap-PCR method. Characterization of beta-thalassemia mutations was made by direct genomic sequencing of the beta-globin gene amplified through polymerase chain reaction (PCR). Haplotypes were determined by analysis of six polymorphic restriction sites [(1) XmnI-5'gammaG, (2) HindIII-gammaG, (3) HindIII-gammaA, (4) HincII-psibeta, (5) HincII-3'psibeta, and (6) HinfI-5'beta] followed by restriction digestion and agarose gel electrophoresis. Twenty-one patients (16%) presented -alpha3.7 thalassemia. Sixteen of those (76%) were heterozygous (-alpha3.7/alphaalpha) and 5 (24%) were homozygous (-alpha3.7/-alpha3.7). -Alpha(4.2), -alpha(20.5) and -(MED) deletions were not found. Nine cases of sickle cell-beta thalassemia were found and four different beta-thal mutations were identified: beta(+) -88 (C>T), 3.8%; beta(+) codon 24 (T > A), 1.5%; beta(+) IVSI-110 (G > A), 0.7% and beta (IVSI-1 (G > A), 0.7%. No differences according to age were observed in -alpha(3.7) deletion, beta-thalassemia and HHB*S haplotypes distribution. Our results suggest that although alpha- and beta-thalassemia and betaS haplotypes may have modulating effect on clinical expression and hematological parameters of SCA, these genetic variables probably have little influence on the subjects' survival.

  15. [Mesenteric venous trombosis and pregnancy--a case report and a short review of the problem]. (United States)

    Terzhumanov, R; Uchikova, E; Paskaleva, V; Milchev, N; Uchikov, A


    Mesenteric venous thrombosis is extremely rare surgical pathology during pregnancy and frequently is associated with hemoglobinopathies beta-thalassemia, congenital defects of the coagulation and antiphospholipide syndrome. It has nontypical clinical appearance, which hardens the timely diagnosis and the adequate surgical treatment. We present a case of a 22 year-old girl with hemozygote form of beta thalassemia, pregnant in ml II, with mesenteric venose thrombosis. The diagnosis was made on the 24th hour from the beginning of the disease. The patient was operated successfully by a resection of the necrotic changed part of the intestine. She noticed vaginal bleeding due to a missed abortion on the 22nd day after the operation.

  16. Hydroxyurea in the management of thalassemia intermedia. (United States)

    Karimi, Mehran


    Hydroxyurea (HU) is an antineoplastic agent that enhances fetal hemoglobin. The clinical significance induced by this compound is well known in sickle cell disease. This clinical significance could also be expected in beta-thalassemia patients. Although studies on beta-thalassemia major patients showed significant results, but these clinical responses are expected to be more in thalassemia intermedia (TI) patients because of lesser alpha/beta globin imbalance. Studies showed that HU therapy in TI patients has significant effects on increasing Hb levels that can cause reducing blood transfusion dependency and transfusion free in some patients, decreasing skeletal deformities and splenomegaly and increasing energy state. So HU therapy could be a useful alternative to blood transfusion in some TI patients.

  17. Diversity of [beta]-globin mutations in Israeli ethnic groups reflects recent historic events

    Energy Technology Data Exchange (ETDEWEB)

    Filon, D.; Oron, V.; Krichevski, S.; Shaag, A.; Goldfarb, A.; Aker, M.; Rachmilewitz, E.A.; Rund, D.; Oppenheim, A. (Hebrew Univ. Hadassah-Medical School, Jerusalem (Israel)) (and others)


    The authors characterized nearly 500 [beta]-thalassemia genes from the Israeli population representing a variety of ethnic subgroups. They found 28 different mutations in the [beta]-globin gene, including three mutations ([beta][sup S], [beta][sup C], and [beta][sup O-Arab]) causing hemoglobinopathies. Marked genetic heterogeneity was observed in both the Arab (20 mutations) and Jewish (17 mutations) populations. On the other hand, two ethnic isolates - Druze and Samaritans - had a single mutation each. Fifteen of the [beta]-thalassemia alleles are Mediterranean in type, 5 originated in Kurdistan, 2 are of Indian origin, and 2 sporadic alleles came from Europe. Only one mutant allele-nonsense codon 37-appears to be indigenous to Israel. While human habitation in Israel dates back to early prehistory, the present-day spectrum of [beta]-globin mutations can be largely explained by migration events that occurred in the past millennium. 26 refs., 2 figs., 3 tabs.

  18. [Hereditary spherocytosis: Review. Part I. History, demographics, pathogenesis, and diagnosis]. (United States)

    Donato, Hugo; Crisp, Renée Leonor; Rapetti, María Cristina; García, Eliana; Attie, Myriam


    Hereditary spherocytosis is the most frequent hereditary anemia excluding beta thalassemia in Argentina. Historical, demographic, genetic and pathogenic aspects of the disease are reviewed, and confirmatory laboratory tests are described. Special characteristics on the outcome of the disease in our population and prevalent protein deficiencies in our country are described. Emphasis is given on new available laboratory tests, which allow an earlier diagnosis using volume of blood samples significantly smaller than required for conventional tests.

  19. Study of ocular manifestations in children of thalassemia

    Directory of Open Access Journals (Sweden)

    Dhara K. Gosai


    Conclusion: Most of the ocular changes of beta thalassemia are attributed to the course and severity of the disease. Reduction in serum iron and serum Ferritin levels by iron- chelating agents and regular ocular examination to look for side-effects of such agents can aid in preventing or delaying ocular complications. [Int J Res Med Sci 2014; 2(2.000: 695-698

  20. Deferasirox, an oral chelator in the treatment of iron overload


    I. Portioli


    BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years o...

  1. beta-thalassaemia major hos børn og unge i Danmark

    DEFF Research Database (Denmark)

    Jung, Anne; Main, Katharina Maria; Scheibel, Elma;


    strategy. MATERIAL AND METHODS: During 1998-99 all Danish pediatric departments were contacted for identification of children aged 0-18 years with beta-thalassemia major. Blood transfusions and chelation therapy were registered, and for Eastern Denmark clinical, endocrine, cardiac, and serologic parameters....... An earlier and more effective iron chelation therapy together with improved patient support may reduce growth disturbances and endocrine and cardiac late effects. Udgivelsesdato: 2002-Dec-2...

  2. Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate



    Iron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate c...

  3. Sickle-β+ thalassemia with splenic calcification and bone marrow infarction: a case report



    We came across an unusual case of a 20 years old male from north India who presented with repeated episodes of pyrexia of unknown origin (PUO) and history of chronic hemolytic anemia. On investigation he was detected to have Sickle-β+ Thalassemia and subtle features of hyposplenism. Radiological investigations revealed extensive splenic calcification and bone marrow examination to evaluate for PUO showed extensive bone marrow infarction and fibrosis. Molecular diagnosis for beta thalassemia m...


    Asadov, Ch; Alimirzoyeva, Z; Hasanova, M; Mammadova, T; Shirinova, A


    Research objective is to study the efficacy of recombinant erythropoietin (epoetin alfa) as alternative method of treatment beta-thalassemia intermedia. Study involved 58 patients with beta-thalassemia intermedia (23 women and 35 men). In all observed patients was defined levels of hemoglobin (Hb), red blood cells (RBC), erythrocyte indexes (MCV, MCH, MCHC), hemoglobin fractions (HbA, HbA2, HbF), serum ferritin, serum erythropoietin before and after administrated rEPO. All patients received rEPO during 6 month at the dose - 10000 IU subcutaneously. The majority of patients - 39 (67%) had a good response to rEPO (increase in hemoglobin level more than 20 g/l); 16 patients (28%) had a mean response (increase in Hb 10 - 20 g/l); in 3 (5%) patients occurred poor response to rEPO therapy (increase in Hb <10 g/l). After rEPO treatment of beta-thalassemia intermedia patients there was a statistically significant change in the number of RBC, levels of HbF and sEPO. The evaluation of interdependence between the indices of the baseline sEPO and increased Hb values in patients after rEPO treatment revealed the presence of the reverse direct relationship (r=-0.67). Based on the results, it can be concluded that the use of rEPO in complex therapy of beta-thalassemia intermedia leads to increased levels of Hb and consequently reducing the need for blood transfusions, and accordingly expected to prevent severe complications of blood transfusion (alloimmunization, hypersplenism, iron overload, contamination transmissible infections) facilitating normal growth and development, and a better quality of life.

  5. Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy


    SOLIMAN, Ashraf; Yassin, Mohamed; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; De Sanctis, Vincenzo


    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The rece...

  6. A molecular epidemiologic study of thalassemia using newborns' cord blood in a multiracial Asian population in Singapore: results and recommendations for a population screening program. (United States)

    Kham, S K; Yin, Shirley Kham Kow; Quah, Thuan Chong; Loong, Ai Mei; Tan, Poh Lin; Fraser, Angus; Chong, S S; Chuan, Samuel Chong Siong; Yeoh, A E; Eng-Juh, Allen Yeoh


    DNA technology provides a new avenue to perform neonatal screening tests for single-gene diseases in populations of high frequency. Thalassemia is one of the high-frequency single-gene disorders affecting Singapore and many countries in the malaria belt. The authors explored the feasibility of using PCR-based diagnostic screening on 1,116 unselected sequential cord blood samples for neonatal screening. The cord blood samples were screened for the most common reported alpha- and beta-thalassemia mutations in each ethnic group (Chinese, Malays, and Indians) in a multiracial population. The carrier frequency for alpha-thalassemia mutations was about 6.4% in the Chinese (alpha deletions = 3.9%, alpha deletions = 2.5%), 4.8% in Malays, and 5.2% in Indians. Only alpha deletions were observed in the Chinese. The carrier frequency for beta-thalassemia mutations was 2.7% in the Chinese, 6.3% in Malays, and 0.7% in Indians. Extrapolating to the population distribution of Singapore, the authors found a higher overall expected carrier frequency for alpha- and beta-thalassemia mutations of 9% compared with a previous population study of 6% by phenotype. The highly accurate results make this molecular epidemiologic screening an ideal method to screen for and prevent severe thalassemia in high-risk populations.

  7. 45例少见β地中海贫血患者β球蛋白基因序列分析%Study on rate gene mutation of β -thalassemia

    Institute of Scientific and Technical Information of China (English)

    宋春林; 赖金甜; 范菊花; 郭晓玲; 陈淑芬


    目的 研究佛山地区稀有β地中海贫血基因突变.方法 对来佛山妇幼保健院产前检查的8400例患者进行血细胞和血红蛋白电泳常规筛查,对其中3600例血象异常怀疑β地中海贫血的患者行反向点杂交检测常见的17种突变,确诊1260例,然后对未发现常见突变的45例可疑患者扩增β球蛋白基因送公司直接基因测序.结果 发现了15例稀有β地中海贫血,其中nt-90(C→T)、CD6(GAG→AAG)突变各2例,IVS-I-116(T→G)、IVS-I-128(T→G)、IVS-I-130(G→C)突变各1例,CD113(GTG→GAG)突变8例.结论 针对未发现常见17种β地中海贫血基因突变的可疑患者采用β球蛋白基因直接基因测序鉴定可以发现稀有突变,并为患者更好地提供产前基因诊断服务.%Objective To detect the rare gene mutation of β-thalassemia in Foshan area. Methods Basic erythrocyte hematologic parameters were performed through auto cell counter Sysmex XT2000i in routine for all 8400 patients who came to Foshan Maternal and Children's Hospital for prenatal screen. And Hb electrophoresis were carried out through auto analyzer Helena Spire 3000. Then identified the commonest known 17 types beta thalassemia mutations by reverse dot blot hybridization for the 3600 patients whose erythrocyte parameters were associated with hypochromia or whose electrophoresis results had elevated HbA2 or HbF or abnormal band. 1260 cases were identified as beta thalassemia. For the 45 doubtful patients who were not found the commonest known 17 types beta thalassemia mutations, direct DNA sequencing of the entire β-globin gene was performed. Results There were 45 patients were associate with hypochromia and had elevated HbA2 or HbF or abnormal band who were not found the commonest 17 types beta thalassemia mutations by reverse dot blot hybridization. After sequencing the entire beta globin gene, 15 rare beta thalassemia gene mutations were found, of which 2 cases were nt-90 (C→T), 2 cases were

  8. Microcytic hypochromic anemia patients with thalassemia : Genotyping approach

    Directory of Open Access Journals (Sweden)

    Rahim Fakher


    Full Text Available Background: Microcytic hypochromic anemia is a common condition in clinical practice, and alpha-thalassemia has to be considered as a differential diagnosis. Aims: This study was conducted to evaluate the frequency of α-gene, β-gene and hemoglobin variant numbers in subjects with microcytic hypochromic anemia. Setting And Designs: Population-based case-control study in the Iranian population. Materials And Methods: A total of 340 subjects from southwest part of Iran were studied in the Research Center of Thalassemia and Hemoglobinopathies (RCTH, Iran. Genotyping for known a- and b-gene mutations was done with gap-PCR and ARMS. In cases of some rare mutations, the genotyping was done with the help of other techniques such as RFLP and ARMS-PCR. Statistical Analysis: Statistical analysis was carried out by SPSS 11.5 and an independent-sample t test. Results: Out of the total 340 individuals, 325 individuals were evaluated to have microcytic hypochromic anemia based on initial hematological parameters such as MCV< 80 fl; MCH < 27 pg; the remaining 15 patients were diagnosed with no definite etiology. The overall frequency of -α3.7 deletion in 325 individuals was 20.3%. The most frequent mutations were IVS II-I, CD 36/37 and IVS I-110 with frequencies of 6.31%, 5.27% and 1.64%, respectively. Only, there was a significant difference between beta-thalassemia trait and beta-thalassemia major with regard to MCV (P < 0.05 and MCH (P < 0.05 indices, and also MCH index between beta-thalassemia trait and Hb variants (P < 0.05. Conclusion: Molecular genotyping provides a rapid and reliable method for identification of common, rare and unknown a- and b-gene mutations, which help to diagnose unexplained microcytosis and thus prevent unnecessary iron supplementation.

  9. Multiple transfused thalassemia major: Ocular manifestations in a hospital-based population

    Directory of Open Access Journals (Sweden)

    Taneja Rashi


    Full Text Available Purpose: To study the ocular manifestations in multiple transfused beta-thalassemia major patients and assess the ocular side-effects of iron chelating agents. Materials and Methods: In this prospective observational study, 45 multiple transfused beta-thalassemia major children between six months and 21 years of age were enrolled and assigned groups according to the treatment regimens suggested. Group A received only blood transfusions, Group B blood transfusions with subcutaneous desferrioxamine, Group C blood transfusions with desferrioxamine and oral deferriprone and Group D blood transfusions with deferriprone. Ocular status at the time of enrolment was documented. Subjects were observed quarterly for one year for changes in ocular status arising due to the disease process and due to iron chelation therapy. Children with hemoglobinopathies other than beta-thalassemia major, congenital ocular anomalies and anemia due to other causes were excluded. Results: Ocular involvement was observed in 58% of patients. Lenticular opacities were the most common ocular finding (44%, followed by decreased visual acuity (33%. An increased occurrence of ocular changes was observed with increase of serum ferritin and serum iron levels as well as with higher number of blood transfusions received. Desferrioxamine seemed to have a protective influence on retinal pigment epithelium (RPE mottling. Occurrence of lenticular opacities and RPE degeneration correlated positively with use of desferrioxamine and deferriprone respectively. Follow-up of patients for one year did not reveal any change in ocular status. Conclusion: Regular ocular examinations can aid in preventing, delaying or ameliorating the ocular complications of thalassemia.

  10. A novel murine model of Cooley anemia and its rescue by lentiviral-mediated human beta-globin gene transfer. (United States)

    Rivella, Stefano; May, Chad; Chadburn, Amy; Rivière, Isabelle; Sadelain, Michel


    Patients affected by beta-thalassemia major require lifelong transfusions because of insufficient or absent production of the beta chain of hemoglobin (Hb). A minority of patients are cured by allogeneic bone marrow transplantation. In the most severe of the hitherto available mouse models of beta-thalassemia, a model for human beta-thalassemia intermedia, we previously demonstrated that globin gene transfer in bone marrow cells is curative, stably raising Hb levels from 8.0-8.5 to 11.0-12.0 g/dL in long-term chimeras. To fully assess the therapeutic potential of gene therapy in the context of a lethal anemia, we now have created an adult model of beta(0)-thalassemia major. In this novel model, mice engrafted with beta-globin-null (Hbb(th3/th3)) fetal liver cells succumb to ineffective erythropoiesis within 60 days. These mice rapidly develop severe anemia (2-4 g/dL), massive splenomegaly, extramedullary hematopoiesis (EMH), and hepatic iron overload. Remarkably, most mice (11 of 13) treated by lentivirus-mediated globin gene transfer were rescued. Long-term chimeras with an average 1.0-2.4 copies of the TNS9 vector in their hematopoietic and blood cells stably produced up to 12 g/dL chimeric Hb consisting of mu alpha(2):hu beta(2) tetramers. Pathologic analyses indicated that erythroid maturation was restored, while EMH and iron overload dramatically decreased. Thus, we have established an adult animal model for the most severe of the hemoglobinopathies, Cooley anemia, which should prove useful to investigate both genetic and pharmacologic treatments. Our findings demonstrate the remarkable efficacy of lentivirus-mediated globin gene transfer in treating a fulminant blood disorder and strongly support the efficacy of gene therapy in the severe hemoglobinopathies.

  11. Changes in bone micro-architecture and biomechanical properties in the th3 thalassemia mouse are associated with decreased bone turnover and occur during the period of bone accrual (United States)

    Vogiatzi, Maria G.; Tsay, Jaime; Verdelis, Kostas; Rivella, Stefano; Grady, Robert W; Doty, Stephen; Giardina, Patricia J; Boskey, Adele L


    Osteoporosis and fractures occur frequently in patients with beta thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the beta chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse beta chain genes. The heterozygote th3/+ mouse has moderate anemia, and serves as a model of beta thalassemia intermedia (TI), which represents the mild thalassemia phenotype. The th3/th3 mouse has lethal anemia and is a model of beta thalassemia major (TM), which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls: i) Micro-CT of trabecular bone showed decreased bone volume fraction, number of trabeculae and trabecular thickness in both th3/+ and th3/th3 (p<0.05). ii) Cortical bone analysis showed thinner cortices and increased marrow area in th3/+ animals (p<0.05). iii) Micro-CT abnormalities in th3/+ mice were present by 2 months and did not worsen with age. iv) Histomorphometry was significant for decreased bone formation and resorption in both th3/+ and th3/th3. Similarly, cathepsin K and osteocalcin expression from bone of both th3/+and th3/th3 animals was reduced (p<0.05). vi) Biomechanics showed reduced maximum load, maximum moment and structural stiffness in both th3/+and th3/th3 (p<0.01). In conclusion, the th3 mouse model of thalassemia manifests bone changes reminiscent of those in humans, and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover, and develop early on during the period of bone accrual. PMID:20449578

  12. Changes in bone microarchitecture and biomechanical properties in the th3 thalassemia mouse are associated with decreased bone turnover and occur during the period of bone accrual. (United States)

    Vogiatzi, Maria G; Tsay, Jaime; Verdelis, Kostas; Rivella, Stefano; Grady, Robert W; Doty, Stephen; Giardina, Patricia J; Boskey, Adele L


    Osteoporosis and fractures occur frequently in patients with beta-thalassemias, a group of congenital hemolytic anemias characterized by decreased synthesis of the beta chain of hemoglobin. In this study, we determined the bone abnormalities of the th3 thalassemia mouse, generated by deletion of the mouse beta-chain genes. The heterozygous th3/+ mouse has moderate anemia and serves as a model of beta-thalassemia intermedia, which represents the mild thalassemia phenotype. The th3/th3 mouse has lethal anemia and is a model of beta-thalassemia major, which is characterized by life-threatening anemia requiring regular transfusions to sustain life. Compared to controls, (1) microCT of trabecular bone showed decreased bone volume fraction, number of trabeculae, and trabecular thickness in both th3/+ and th3/th3 (P < 0.05); (2) cortical bone analysis showed thinner cortices and increased marrow area in th3/+ (P < 0.05); (3) microCT abnormalities in th3/+ mice were present by 2 months and did not worsen with age; (4) histomorphometry was significant for decreased bone formation and resorption in both th3/+ and th3/th3, and expression of cathepsin K and osteocalcin from bone of both th3/+ and th3/th3 animals was reduced (P < 0.05); (5) biomechanics showed reduced maximum load, maximum moment, and structural stiffness in both th3/+ and th3/th3 (P < 0.01). In conclusion, the th3 mouse model of thalassemia manifests bone changes reminiscent of those in humans and can be used for further bone studies in thalassemia. Bone changes are associated with decreased bone turnover and develop early during the period of bone accrual.

  13. Effects of iron and copper overload on the human liver: an ultrastructural study. (United States)

    Fanni, D; Fanos, V; Gerosa, C; Piras, M; Dessi, A; Atzei, A; Van, Eyken P; Gibo, Y; Faa, G


    Iron and copper ions play important roles in many physiological functions of our body, even though the exact mechanisms regulating their absorption, distribution and excretion are not fully understood. Metal-related human pathology may be observed in two different clinical settings: deficiency or overload. The overload in liver cells of both trace elements leads to multiple cellular lesions. Here we report the main pathological changes observed at transmission electron microscopy in the liver of subjects affected by Beta-thalassemia and by Wilson's disease. The hepatic iron overload in beta-thalassemia patients is associated with haemosiderin storage both in Kupffer cells and in the cytoplasm of hepatocytes. Haemosiderin granules are grouped inside voluminous lysosomes, also called siderosomes. Other ultrastructural changes are fat droplets, proliferation of the smooth endoplasmic reticulum and fibrosis. Apoptosis of hepatocytes and infiltration of sinusoids by polymorphonucleates is also detected in beta-thalassemia. Ultrastructural changes in liver biopsies from Wilson's disease patients are characterized by severe mitochondrial changes, associated with an increased number of perossisomes, cytoplasmic lipid droplets and the presence of lipolysosomes, characteristic cytoplasmic bodies formed by lipid vacuoles surrounded by electron-dense lysosomes. In patients affected by Wilson's disease, nuclei are frequently involved, with disorganization of the nucleoplasm and with glycogen inclusions. On the contrary, no significant changes are detected in Kupffer cells. Our data show that iron and copper, even though are both transition metals, are responsible of different pathological changes at ultrastructural level. In particular, copper overload is associated with mitochondrial damage, whereas iron overload only rarely may cause severe mitochondrial changes. These differences underlay the need for further studies in which biochemical analyses should be associated with

  14. Serum ferritin levels, socio-demographic factors and desferrioxamine therapy in multi-transfused thalassemia major patients at a government tertiary care hospital of Karachi, Pakistan

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    Rehman Anis


    Full Text Available Abstract Background Beta thalassemia is the most frequent genetic disorder of haemoglobin synthesis in Pakistan. Recurrent transfusions lead to iron-overload manifested by increased serum Ferritin levels, for which chelation therapy is required. Findings The study was conducted in the Pediatric Emergency unit of Civil Hospital Karachi after ethical approval by the Institutional Review Board of Dow University of Health Sciences. Seventy nine cases of beta thalassemia major were included after a written consent. The care takers were interviewed for the socio-demographic variables and the use of Desferrioxamine therapy, after which a blood sample was drawn to assess the serum Ferritin level. SPSS 15.0 was employed for data entry and analysis. Of the seventy-nine patients included in the study, 46 (58.2% were males while 33 (41.8% were females. The mean age was 10.8 (± 4.5 years with the dominant age group (46.2% being 10 to 14 years. In 62 (78.8% cases, the care taker education was below the tenth grade. The mean serum Ferritin level in our study were 4236.5 ng/ml and showed a directly proportional relationship with age. Desferrioxamine was used by patients in 46 (58.2% cases with monthly house hold income significant factor to the use of therapy. Conclusions The mean serum Ferritin levels are approximately ten times higher than the normal recommended levels for normal individuals, with two-fifths of the patients not receiving iron chelation therapy at all. Use of iron chelation therapy and titrating the dose according to the need can significantly lower the iron load reducing the risk of iron-overload related complications leading to a better quality of life and improving survival in Pakistani beta thalassemia major patients. Conflicts of Interest: None

  15. Surgical, non-traumatic splenopathies

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    Ivonne López Masó


    Full Text Available As our modern-day understanding about the role of the spleen in the immune system has developed, indications for splenectomies have also changed. Illnesses like idiopatic thrombocytopenic purple, hereditary spherocytosis, sickle cell anemia, beta thalassemia, portal hypertension and other non-traumatic disseases that carry out with congestive splenomegaly and hypersplenism, find an effective alternative with the total or partially splenectomy. We presented the Good Clinical Practices Guideline for Portal hypertension, approved by consensus in the 4th National Good Clinical Practices Workshop in Pediatric Surgery (Las Tunas, Cuba, March, 2005.

  16. Correction of a splice-site mutation in the beta-globin gene stimulated by triplex-forming peptide nucleic acids

    DEFF Research Database (Denmark)

    Chin, Joanna Y; Kuan, Jean Y; Lonkar, Pallavi S


    Splice-site mutations in the beta-globin gene can lead to aberrant transcripts and decreased functional beta-globin, causing beta-thalassemia. Triplex-forming DNA oligonucleotides (TFOs) and peptide nucleic acids (PNAs) have been shown to stimulate recombination in reporter gene loci in mammalian...... DNA fragments, can promote single base-pair modification at the start of the second intron of the beta-globin gene, the site of a common thalassemia-associated mutation. This single base pair change was detected by the restoration of proper splicing of transcripts produced from a green fluorescent...

  17. Therapeutic globin gene delivery using lentiviral vectors. (United States)

    Rivella, Stefano; Sadelain, Michel


    The severe hemoglobinopathies, including beta-thalassemia major and sickle cell anemia, are candidate diseases for a genetic treatment based on the transfer of a regulated globin gene in autologous hematopoietic stem cells. Two years ago, May et al reported that an optimized beta-globin transcription unit containing multiple proximal and distal regulatory elements harbored by a recombinant lentiviral vector could efficiently integrate into murine hematopoietic stem cells and express therapeutic levels of the human beta-globin gene. Here, we review the advantages afforded by lentivirus-mediated globin gene transfer and recent studies based on this strategy.

  18. The Hematopoietic Stem Cell Therapy for Exploration of Deep Space (United States)

    Ohi, Seigo; Roach, Allana-Nicole; Fitzgerald, Wendy; Riley, Danny A.; Gonda, Steven R.


    It is hypothesized that the hematopoietic stem cell therapy (HSCT) might countermeasure various space-caused disorders so as to maintain astronauts' homeostasis. If this were achievable, the HSCT could promote human exploration of deep space. Using animal models of disorders (hindlimb suspension unloading system and beta-thalassemia), the HSCT was tested for muscle loss, immunodeficiency and space anemia. The results indicate feasibility of HSCT for these disorders. To facilitate the HSCT in space, growth of HSCs were optimized in the NASA Rotating Wall Vessel (RWV) culture systems, including Hydrodynamic Focusing Bioreactor (HFB).

  19. Acute lymphoblastic leukemia in children with associated genetic conditions other than Down's syndrome. The AIEOP experience. (United States)

    Ziino, Ottavio; Rondelli, Roberto; Micalizzi, Concetta; Luciani, Matteo; Conter, Valentino; Aricò, Maurizio


    We retrospectively reviewed the databases of seven studies on acute lymphoblastic leukemia (ALL) by the Associazione Italiana Ematologia Oncologia Pediatrica (AIEOP) to identify patients with associated genetic disease, other than Down's syndrome. Forty-two patients were reported to have associated genetic conditions that included beta-thalassemia (n=10), ataxia-telangiectasia (n=5), neurofibromatosis (n=3), Sotos syndrome (n=2) and other individual conditions. Patients with ataxia-telangiectasia, all with T-cell ALL, had a higher frequency of adverse events.

  20. Total Antioxidant Status in Patients with Major β-Thalassemia

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    Lili Koochakzadeh


    Full Text Available Objective:Beta-thalassemia major is an autosomal recessive disease causing severe and hemolytic anemia, which begins about 2-6 months after birth. Iron overload, which arises from recurrent transfusion and ineffective erythropoiesis, can enhance oxidative stress in thalassemic patients. The aim of this study was to evaluate the serum total antioxidant capacity of patients with ß-Thalassemia major. Methods:Sixty six Iranian patients with β-thalassemia major and 66 age-gender matched controls were evaluated for serum total antioxidant status (TAS, uric acid (UA, bilirubin and albumin. In addition, serum ferritin and transaminases were recorded in these subjects. Findings: Significant increases of TAS, UA, and bilirubin were observed in the patient group, compared with the control group (P<0.01. Mean TAS and bilirubin in male patients was higher than in females (P=0.005 and P=0.008, respectively. There was also direct correlation between TAS and albumin (P<0.001, bilirubin (P<0.001 and UA (P=0.002. Conclusion: Endogenous antioxidants such as ferritin, UA and bilirubin can result in increased level of TAS in the patients with Beta-thalassemia major. Compensatory excess of TAS to oxidative stress could also be the reason for difference between our findings and previous studies.

  1. Hemoglobinopatias no Distrito Federal, Brasil

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    J. Tavares-Neto


    Full Text Available Em uma amostra de 3137 pessoas, residentes no Distrito Federal, foram detectadas as seguintes hemoglobinas: em 3009(95,92% HbAA; em 91 (2,90% HbAS; em 20(0,64% HbAC; em 8 (0,26% talassemia beta minor; em 5(0,16% HbAJ alfa; em 3 (0,09% HbAM e em 1 (0,03% talassemia major associada com HbAS. A HbAS têm as seguintes freqüências, quanto ao grupo racial: branco - 1,84%; mulato claro 2,55%; mulato médio-3,68%; mulato escuro - 6,80%; negro -10,43% e mestiço de índio -3,85%.The hemoglobins of 3137 persons from the Federal District, Brazil was studied. The identified types of hemoglobins were: HbAA (3009 - 95,92%; HbAS (91 - 2,90%; HbAC (20 - 0,64% beta thalassemia minor (8 - 0,26%; HbAJ alpha (5 - 0,16%; HbAM (3 - 0,09% and beta thalassemia major/HbS (1 - 0,03%. The frequencies of sickle cell trait (HbAS of each racial class were: white (1,84%; light mulatto (2,55%; medium mulatto (3,68%; dark mulatto(6,80%, negro (10,43%and indian mestizo (3,85%.

  2. Mosaic segmental uniparental isodisomy and progressive clonal selection: a common mechanism of late onset β-thalassemia major (United States)

    Harteveld, Cornelis L.; Refaldi, Chiara; Giambona, Antonino; Ruivenkamp, Claudia A. L.; Hoffer, Mariëtte J. V.; Pijpe, Jeroen; De Knijff, Peter; Borgna-Pignatti, Caterina; Maggio, Aurelio; Cappellini, Maria D.; Giordano, Piero C.


    Genomic DNA of 3 patients, born as healthy carriers and developing a late-onset severe transfusion-dependent beta-thalassemia major was studied by high-density genome wide SNP array analysis. A mosaic loss of heterozygosity for almost the entire 11p was found, not attributable to deletions but involving mosaicism for segmental paternal isodisomy of 11p. Mitotic recombination leading to mosaic segmental uniparental isodisomy on chromosome 11p in multiple tissues has been described as a molecular disease mechanism for a subset of sporadic Beckwith-Wiedemann syndrome cases. A similar mechanism also seems to be involved in causing late-onset disease in carriers of recessive mutations in other genes located in 11p, such as late-onset beta-thalassemia major and sickle cell disease. We suggest that the loss of maternally imprinted IGF-2 and H19 genes may account for the selective advantage of hematopoietic cells containing this segmental paternal isodisomy of 11p carrying the β-thalassemia mutation. PMID:22983591

  3. T2* magnetic resonance imaging of the liver in thalassemic patients in Iran

    Institute of Scientific and Technical Information of China (English)

    Farhad Zamani; Sara Razmjou; Shahram Akhlaghpoor; Seyyedeh-Masoomeh Eslami; Azita Azarkeivan; Afsaneh Amiri


    AIM: To investigate the accuracy of T2*-weighted magnetic resonance imaging (MRI T2*) in the evaluation of iron overload in beta-thalassemia major patients. METHODS: In this cross-sectional study, 210 patients with beta-thalassemia major having regular blood transfusions were consecutively enrolled. Serum ferritin levels were measured, and all patients underwent MRI T2* of the liver. Liver biopsy was performed in 53 patients at an interval of no longer than 3 mo after the MRIT2* in each patient. The amount of iron was assessed in both MRI T2* and liver biopsy specimens of each patient. RESULTS: Patients' ages ranged from 8 to 54 years with a mean of 24.59 ± 8.5 years. Mean serum ferritin level was 1906 ± 1644 ng/mL. Liver biopsy showed a moderate negative correlation with liver MRI T2* (r = -0.573, P = 0.000) and a low positive correlation with ferritin level (r = 0.350, P = 0.001). Serum ferritin levels showed a moderate negative correlation with liver MRI T2* values (r = -0.586, P = 0.000). CONCLUSION: Our study suggests that MRI T2* is a non-invasive, safe and reliable method for detecting iron load in patients with iron overload. . 2011 Baishideng. All rights reserved.

  4. Frequency of Thalassemia in Iran and Khorasan Razavi

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    Gholam Hasan Khodaei


    Full Text Available Introduction: Beta-thalassemia is the most common hereditary disease in Iran. More than two million carriers of beta-thalassemia live in Iran. Since the Iranian population is a mixture of different ethnic groups, it is necessary to determine the frequency  in the different parts of the country. Materials and Methods: This descriptive study is a cross sectional study with helping by professional groups fighting diseases in Khorasan Razavi province.   Results: In Iran, according to World Health Organization, about 4 percent of the population, are carriers of the thalassemia gene. In other words, about 2-3 million people are suffering from thalassemia minor.Now, more than 18 thousand cases of thalassemia are scattered across the country in different provinces, are different. Mazandaran, Gilan, Hormozgan, Khuzestan, kohgiloyeh, Fars, Bushehr, Sistan and Baluchestan, Kerman and Isfahan, are 10 provinces with high prevalence in our country. We have 342 cases of thalassemia major in Khorasan Razavi province.   Conclusion: Prevalence  of thalassemia in our country is 3.6%  and Iran is located on the belt of thalassemia and due to a history of consanguinity, this disease has a prevalence of 0.6% among in the provinces of Khorasan Razavi.

  5. Deferasirox, an oral chelator in the treatment of iron overload

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    I. Portioli


    Full Text Available BACKGROUND Deferasirox is a once-daily oral iron chelator developed for treating iron overload complicating long-term transfusion therapy in patients with diseases such as beta-thalassemia and myelodysplastic syndromes. Iron overload can damage the liver, pancreas and the heart. Deferoxamine, the only other drug approved for iron chelation, can prevent these effects but requires parenteral administration. Deferasirox has been approved after a one-year, open-label trial in patients ≥ 2 years old with beta-thalassemia and transfusional emosiderosis randomized to once-daily oral 5, 10, 20, 30 mg/kg/day in comparison of subcutaneous deferoxamine 20-60 mg/mg/kg/day x 5/week. CONCLUSIONS Deferasirox 20-30 mg/kg/day produced reductions in liver iron concentration (LIC similar to those with deferoxamine. Adverse effect of deferasirox (increases of serum creatinine and aminotransferases, including the gastrointestinal ones, are similar but more frequent than those occurring with deferoxamine. Information is lacking on the effects of deferasirox on cardiac iron and cardiac dysfunction which is the most serious complication of transfusional iron overload.

  6. Chelation Therapy with Oral Solution of Deferiprone in Transfusional Iron-Overloaded Children with Hemoglobinopathies

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    Alexandros Makis


    Full Text Available Iron overload in hemoglobinopathies is secondary to blood transfusions, chronic hemolysis, and increased iron absorption and leads to tissue injury requiring the early use of chelating agents. The available agents are parenteral deferoxamine and oral deferiprone and deferasirox. There are limited data on the safety and efficacy of deferiprone at a very young age. The aim of our study was the presentation of data regarding the use of oral solution of deferiprone in 9 children (mean age 6.5, range 2–10 with transfusion dependent hemoglobinopathies (6 beta thalassemia major, 1 thalassemia intermedia, and 2 sickle cell beta thalassemia. The mean duration of treatment was 21.5 months (range 15–31. All children received the oral solution without any problems of compliance. Adverse reactions were temporary abdominal discomfort and diarrhea (1 child, mild neutropenia (1 child that resolved with no need of discontinuation of treatment, and transient arthralgia (1 child that resolved spontaneously. The mean ferritin levels were significantly reduced at the end of 12 months (initial 2440 versus final 1420 μg/L, . This small study shows that oral solution of deferiprone was well tolerated by young children and its use was not associated with major safety concerns. Furthermore, it was effective in decreasing serum ferritin.

  7. Diagnóstico de hemoglobinopatias em recém-nascidos do Hospital de Base de São José do Rio Preto-SP Diagnosis of hemoglobinopathies in newborn babies in Hospital de Base, São José do Rio Preto, SP, Brazil

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    Fatima A. M. Siqueira


    Full Text Available The neonatal period is considered the most effective for the screening of hemoglobinopathies. This allows prophylaxis and prevention, improving the patient's survival and guidance of parents and heterozygote carriers. The present work aims at the early detection of abnormal hemoglobins, the establishment of standard analysis and to examine the viability of the prevention program. Blood samples were collected by heel stick and from blood cord of children born in the Hospital de Base São José do Rio Preto, from April 1998 to November 1999. Electrophoresis and cytological, biochemical, cromatographic analyses were made for abnormal hemoglobin characterization. A total of 1,478 neonatal blood samples were analyzed in which 14.62% presented with hemoglobins alterations: 3.32% had Hb S; 0.61% had Hb C; 7.44% were suggestive of alpha thalassemia; 1.55% were suggestive of beta thalassemia, and 1.70% had alpha/beta thalassemia interactions. The samples collected from the blood cord showed better results in all analyses while the blood samples collected by heel stick on filter paper, were applicable to only specific methodologies. The routine laboratory methods allowed identification of the thalassemic and variant forms, and isoelectric focusing presented sensitivity only for variant identification in this age range. The suspected cases were reassessed after six months, which permitted genetic counseling of their family members and clinic attendance. A multidisciplinary approach in programs of this kind is fundamental for its success.

  8. [Diagnostic strategy of beta-thalassemic mutation in a Tunisian family, application in prenatal diagnosis]. (United States)

    Khelil, A H; Laradi, S; Ferchichi, S; Carion, N; Béjaoui, M; Saad, A; Chaieb, A; Miled, A; Ben Chibani, J; Perrin, P


    At present, the application of combined methods in molecular biology allows us to carry out the prenatal diagnosis in a more rapid and less onerous manner especially when the family presents an index case. In this study, we have analyzed a family with one case of intermediate beta-thalassemia. First, we have used the denaturing gradient gel electrophoresis (DGGE). Then, we have identified the mutations by the refractory mutation system technique (ARMS PCR) using specific primers for the most frequent mutations in the Tunisian population (codon 39 (C --> T) and IVS-I-2 (T--> G) for beta0 thalassemias and IVS-I-110 (G --> A) for beta+ thalassemias). The analyzed family has shown the IVS-I-110 (G --> A) mutation in the heterozygous state in the mother and the index case. Subsequently, sequencing in the gene revealed a frameshift 8 (-AA) mutation in the father and his daughter. This patient is thus a compound heterozygote Codon 8 (-AA)/IVS-I-110. DGGE and ARMS PCR analysis of foetal DNA extracted from trophoblast culture didn't show any of the two mutations found in the family.

  9. Years Follow-Up

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    Atooshe Rohani


    Full Text Available   Inroduction: Heart failure (HF is an important cause of morbidity and mortality in the cases of Beta-thalassemia major. The purpose of this study was to estimate HF prevalence in these patients and to assess the survivability of those who were treated with intensive chelating therapy.   Design and methods: This cross sectional study included 72 beta-thalassemia major cases, the mean age at the time of referral was 15.7±6.2 years (range 6-35 years and were followed in a prospective 2 year study. A self-reporting symptom questionnaire was administered, a 12-lead ECG was taken and an echocardiography was obtained from all participants. Echocardiography was performed at 6 month intervals or when a new symptom developed. Results: Risk factors (except for iron overload in the study population were hypothyroidism and diabetes mellitus. The male to female ratio was0.75.Twelve patients had left ventricular (LV systolic dysfunction and 57,79% had LV diastolic dysfunction whereas 11,15% had RV failure. Fifty-nine (81% patients had cardiac disease of which diastolic dysfunction was the most common manifestation .Those with systolic dysfunction were older at presentation (22 ± 6 years versus 31 ± 4 years; P

  10. Study of the effect of iron overload on the function of endocrine glands in male thalassemia patients

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    Abdulzahra Mohammed


    Full Text Available Background: Iron overload is an important issue in the state of thalassemic patients due to the harmful effect of high concentration of iron deposited in different tissues in human body including endocrine glands. In the present work, an attempt is carried out to estimate the effect of iron overload in thalassemic patients on the function of endocrine glands through the estimation of their ability to secrete adequate amounts of certain hormones. Materials and Methods: Seventy eight male children with beta-thalassemia, in the age-group of 4-11 years, were enrolled for this research. These children were being treated with frequent transfusions and long-term iron chelation therapy. Thirty age and sex matched children without thalassemia constituted the control group. Ferritin and different hormones were estimated by ELISA technique. Results: The results showed a mild reduction in the function of endocrine glands through the decrease in the level of some hormones. These changes due mainly to the hypoxia and precipitation of iron in certain glands and overlapping with the synthesis or secretion of the hormones. Conclusion: There is a different hormonal disturbances in beta thalassemia patients. Reduction of total body iron store is an important goal of the treatment of thalassemia and measuring the hormones concentration is necessary for the follow up of the thalassemic patients especially during puberty.

  11. Regulation of iron absorption in hemoglobinopathies. (United States)

    Rechavi, Gideon; Rivella, Stefano


    Beta-thalassemia and sickle cell anemia (SCD) represent the most common hemoglobinopathies caused, respectively, by deficient production or alteration of the beta chain of hemoglobin (Hb). Patients affected by the most severe form of thalassemia suffer from profound anemia that requires chronic blood transfusions and chelation therapies to prevent iron overload. However, patients affected by beta-thalassemia intermedia, a milder form of the disease that does not require chronic blood transfusions, eventually also show elevated body iron content due to increased gastrointestinal iron absorption. Even SCD patients might require blood transfusions and iron chelation to prevent deleterious and painful vaso-occlusive crises and complications due to iron overload. Although definitive cures are presently available, such as bone marrow transplantation (BMT), or are in development, such as correction of the disease through hematopoietic stem cell beta-globin gene transfer, they are potentially hazardous procedures or too experimental to provide consistently safe and predictive clinical outcomes. Therefore, studies that aim to better understand the pathophysiology of the hemoglobinopathies might provide further insight and new drugs to dramatically improve the understanding and current treatment of these diseases. This review will describe how recent discoveries on iron metabolism and erythropoiesis could lead to new therapeutic strategies and better clinical care of these diseases, thereby yielding a much better quality of life for the patients.

  12. The Prevalence of Thalassemia Minor in The Aliabad Katool

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    F Niknezhad


    Full Text Available Background & Objectives: Thalassemia syndromes isone of the inherited disorders in which one or more globulin chains are affected. On the basis of clinical symptoms, thalassemias are categorized as minor, intermediate, and major. Minor beta -thalassemia is a mild microcytic hypo chromic anemia; in most cases asymptomatic and HbA2 is more than normal. Materials & Methods: This study carried out on 813 blood samples obtained from male high school students of Aliabad Katool, in the north of Iran. After detecting red blood cell indices of the subjects whose MCV was less than 80fl HbA study performed. Results: The MCV of 8.24% of the subjects was less than 80fl.34 of 67 had HbA2 of less than 3.5 %(normal while the rest more than 3.5%(minor. Conclusions: Since about 50% of microcytic anemic patients were the carrier of beta-thalassemia and it is highly Prevalent in this region (4.06%, we recommend to investigate HbA2 in people with MCV less than 80 fl. Keyword: Thalassemia, Thalassemia minor, HbA2, Iran

  13. Study on effectiveness of transfusion program in thalassemia major patients receiving multiple blood transfusions at a transfusion centre in Western India

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    Shah Neeraj


    Full Text Available Background : Children suffering from beta-thalassemia major require repeated blood transfusions which may be associated with dangers like iron overload and contraction of infections such as HIV, HCV, and HBsAg which ultimately curtail their life span. On the other hand, inadequate transfusions lead to severe anemia and general fatigue and debility. Materials and Methods: Data were obtained from 142 beta-thalassemia major patients aged 3 years or more receiving regular blood transfusions at a transfusion centre in Western India from 1 April 2009 to 30 June 2009. The clinical data and laboratory results were subsequently analyzed. Results: Of the 142 patients, 76 (53.5% were undertransfused (mean Hb <10 gm%. 96 (67% of the patients were taking some form of chelation therapy but out of them only 2 (2% were adequately chelated (S. ferritin <1000 ng/ml. 5 (3.5% of the patients were known diabetics on insulin therapy. 103 (72% of the patients were retarded in terms of growth. The prevalence of transfusion-transmitted infections (TTIs such as HCV, HIV, and HBsAg was respectively 45%, 2%, and 2%, with the prevalence of HCV being significantly more than the general population. The HCV prevalence showed positive correlation with the age of the patients and with the total no of blood transfusions received. As many as 15% (6 out of 40 children who were born on or after 2002 were HCV positive despite the blood they received being subjected to screening for HCV. Conclusions: The study suggests the need to step up the transfusions to achieve hemoglobin goal of 10 gm% (as per the moderate transfusion regimen and also to institute urgent and effective chelation measures with the aim of keeping serum ferritin levels below 1000 ng/ml to avoid the systemic effects of iron overload. In addition, strict monitoring of the children for endocrinopathy and other systemic effects of iron overload should be done. Rigid implementation of quality control measures for the

  14. Genotyping of Kell, Duffy, Kidd and RHD in patients with b Thalassemia

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    Castilho Lilian


    Full Text Available Determination of Rh, Kell, Duffy and Kidd phenotypes in addition to ABO is used to prevent the alloimmunization to red blood cells (RBCs antigens and as part of the antibody identification process in patients with beta Thalassemia. However, phenotyping in these patients can be time consuming and difficult to interpret. In these situations, it would be valuable to have an alternative to hemagglutination tests to determine the patient's antigen profile. We used PCR-RFLP to genotype such patients. DNA was prepared from 50 patients with beta Thalassemia who had been phenotyped by routine hemagglutination, and tested for Kell, Kidd, Duffy/GATA mutation by PCR-RFLP. RHD/non-D was analysed by PCR product size associated to RHD gene sequence in intron 4 and exon 10/3'UTR. The genotyping assays were performed without knowledge of phenotype results. For RHD/non-D, 47 were RhD+ and RHD+/RHCE+, and 3 were RhD- and RHD-/RHCE+. For Kell, 48 kk were K2K2 and 2 Kk were K1K2. For Duffy, of 44 samples that had normal GATA box, 8 Fy(a+b- were FYA/FYA, 15 Fy(a+b+ were FYB/FYB, and 19 Fy(a+b+ were FYA/FYB; of the other 4 samples 3 were FYA/FYB and heterozygous GATA mutation, and 1 Fy(a-b- was FYB/FYB, homozygous GATA mutation. Two samples phenotyped as Fy(a+b- that had normal GATA , presented the 265T/298A mutations and two samples phenotyped as Fy(a-b+ were genotyped was FYA/FYB.. For Kidd , 15 Jk(a+b were JKA/JKA, 12 Jk(a-b+ were JKB/JKB, and 20 Jk(a+b+ were JKA/JKB. Three samples phenotyped as JK(a+b+ were genotyped as JKB/JKB. Genotype is more accurate than phenotype for determination of blood groups in polytransfused patients with betaThalassemia. Genotyping in these patients can be helpful to select antigen-negative RBCs for transfusion.

  15. Molecular characterization of hereditary persistence of fetal hemoglobin in the Karen people of Thailand. (United States)

    Trachoo, Objoon; Sura, Thanyachai; Sakuntabhai, Anavaj; Singhasivanon, Pratap; Krudsood, Srivicha; Phimpraphi, Waraphon; Krasaesub, Somporn; Chanjarunee, Suporn; Looareesuwan, Sornchai


    Hereditary persistence of fetal hemoglobin (HPFH) is the condition whereby a continuously active gamma-globin gene expression leads to elevated fetal hemoglobin (Hb F) levels in adult life [Stamatoyannopoulos G, Grosveld F. Hemoglobin switching. In: Stamatoyannopoulos G, Majerus PW, Perlmutter RM, Varmus H, eds. The Molecular Basis of Blood Diseases. Philadelphia: W.B. Saunders, 2001:135-182; Wood WG. Hereditary persistence of fetal hemoglobin and delta(beta) thalassemia. In: Steinberg MH, Forget BG, Higgs DR, Nagel RL, eds. Disorders of Hemoglobin: Genetics, Pathophysiology, and Clinical Management. Cambridge: Cambridge University Press, 2001:356-388; and Weatherall DJ, Clegg JB. Hereditary persistence of fetal hemoglobin. In: Weatherall DJ, Clegg JB, eds. The Thalassaemia Syndromes. Oxford: Blackwell Scientific Publishers, 1981:450-507]. The condition is caused either by mutation of the beta- and gamma-globin genes, or the gamma-gene controlled region on other chromosomes. Several families with this condition have been reported from Vietnam, Cambodia and China, and the Southeast Asian mutation (or HPFH-6), a 27 kb deletion, was demonstrated. Here we report on a mother and her daughter of the Karen ethnic group with high levels of Hb F, living in the Suan Pueng District on the border of Thailand and Myanmar. Genotyping showed a heterozygosity for the 27 kb deletion of the beta-globin gene. Their conditions have been confirmed by gap polymerase chain reaction (PCR) with three oligonucleotide primers recently developed by Xu et al. [Xu X-M, Li Z-Q, Liu Z-Y, Zhong X-L, Zhao Y-Z, Mo Q-H. Molecular characterization and PCR detection of a deletional HPFH: application to rapid prenatal diagnosis for compound heterozygotes of this defect with beta-thalassemia in a Chinese family. Am J Hematol 2000; 65:183-188.], and a DNA sequencing method. Thus far there has been no official report of the HPFH-6 anomaly from Thailand. The compound heterozygosity of beta-thalassemia (thal

  16. Intrasplenic masses of ``preserved`` functioning splenic tissue in sickle cell disease: correlation of imaging findings (CT, ultrasound, MRI, and nuclear scintigraphy)

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    Levin, T.L. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Berdon, W.E. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Haller, J.O. [Department of Radiology, SUNY Downstate Medical Center, Brooklyn, New York (United States); Ruzal-Shapiro, C. [Department of Radiology, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, 3959 Broadway, BHN 3-318, New York, NY 10032 (United States); Hurlet-Jenson, A. [Department of Pediatrics, Columbia-Presbyterian Medical Center, Babies and Children`s Hospital of New York, New York (United States)


    Purpose. We studied six patients with sickle cell disease (SSD), five homozygous for sickle cell anemia and one with sickle beta-thalassemia, in whom rounded intrasplenic masses proved to be preserved functioning splenic tissue. Materials and methods. Available images including computed tomography, ultrasonography, bone scans (Tc-99m MDP), liver spleen scans (Tc-99m sulfur colloid), and MRI were evaluated. Results. The masses were low density on CT (in an otherwise calcified spleen), hypoechoic relative to the echogenic spleen on US, and had the imaging characteristics of normal spleen on MRI. They failed to accumulate Tc-99m MDP but did demonstrate uptake of Tc-99m sulfur colloid. Conclusion. In a patient with SSD and intrasplenic masses, proper correlation of multiple imaging modalities will establish the diagnosis of functioning splenic tissue and avoid mistaken diagnosis of splenic abscess or infarction. (orig.). With 2 figs., 1 tab.

  17. Targeting the Hepcidin-Ferroportin Axis in the Diagnosis and Treatment of Anemias

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    Elizabeta Nemeth


    Full Text Available The hepatic peptide hormone hepcidin regulates dietary iron absorption, plasma iron concentrations, and tissue iron distribution. Hepcidin acts by causing the degradation of its receptor, the cellular iron exporter ferroportin. The loss of ferroportin decreases iron flow into plasma from absorptive enterocytes, from macrophages that recycle the iron of senescent erythrocytes, and from hepatocytes that store iron, thereby lowering plasma iron concentrations. Malfunctions of the hepcidin-ferroportin axis contribute to the pathogenesis of different anemias. Deficient production of hepcidin causes systemic iron overload in iron-loading anemias such as beta-thalassemia; whereas hepcidin excess contributes to the development of anemia in inflammatory disorders and chronic kidney disease, and may cause erythropoietin resistance. The diagnosis of different forms of anemia will be facilitated by improved hepcidin assays, and the treatment will be enhanced by the development of hepcidin agonists and antagonists.

  18. Non-invasive prenatal diagnosis of β-thalassemia by detection of the cell-free fetal DNA in maternal circulation: a systematic review and meta-analysis. (United States)

    Zafari, Mandana; Kosaryan, Mehrnoush; Gill, Pooria; Alipour, Abbass; Shiran, Mohammadreza; Jalalli, Hossein; Banihashemi, Ali; Fatahi, Fatemeh


    The discovery of fetal DNA (f-DNA) opens the possibility of early non-invasive procedure for detection of paternally inherited mutation of beta-thalassemia. Since 2002, some studies have examined the sensitivity and specificity of this method for detection of paternally inherited mutation of thalassemia in pregnant women at risk of having affected babies. We conducted a systematic review of published articles that evaluated using this method for early detection of paternally inherited mutation in maternal plasma. A sensitive search of multiple databases was done in which nine studies met our inclusion criteria. The sensitivity and specificity was 99 and 99 %, respectively. The current study found that detection of paternally inherited mutation of thalassemia using analysis of cell-free fetal DNA is highly accurate. This method could replace conventional and invasive methods.

  19. Imaging features of thalassemia

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    Tunaci, M.; Tunaci, A.; Engin, G.; Oezkorkmaz, B.; Acunas, G.; Acunas, B. [Dept. of Radiology, Istanbul Univ. (Turkey); Dincol, G. [Dept. of Internal Medicine, Istanbul Univ. (Turkey)


    Thalassemia is a kind of chronic, inherited, microcytic anemia characterized by defective hemoglobin synthesis and ineffective erythropoiesis. In all thalassemias clinical features that result from anemia, transfusional, and absorptive iron overload are similar but vary in severity. The radiographic features of {beta}-thalassemia are due in large part to marrow hyperplasia. Markedly expanded marrow space lead to various skeletal manifestations including spine, skull, facial bones, and ribs. Extramedullary hematopoiesis (ExmH), hemosiderosis, and cholelithiasis are among the non-skeletal manifestations of thalassemia. The skeletal X-ray findings show characteristics of chronic overactivity of the marrow. In this article both skeletal and non-skeletal manifestations of thalassemia are discussed with an overview of X-ray findings, including MRI and CT findings. (orig.)

  20. Hypersensitivity reaction with deferasirox

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    Atul Sharma


    Full Text Available Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case.

  1. Hypersensitivity reaction with deferasirox. (United States)

    Sharma, Atul; Arora, Ekta; Singh, Harmanjit


    Thalassemias comprise a group of hereditary blood disorders. Thalassemia major presents with anemia within the first 2 years of life requiring frequent blood transfusions for sustaining life. Regular blood transfusions lead to iron overload-related complications. Prognosis of thalassemia has improved because of the availability of iron-chelating agents. Oral iron chelators are the mainstay of chelation therapy. Deferasirox is a new-generation oral iron chelator for once daily usage. We herein describe a patient of beta thalassemia major who developed an allergic manifestation in the form of erythematous pruritic skin rashes to the oral iron chelator deferasirox. This is a rare adverse reaction reported with deferasirox that led to a therapeutic dilemma in this particular case.


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    Full Text Available ABSTRACT: Anaemia is a very common problem in our country and iron deficiency is the most common cause especially in the adolescent age group o f girls .Auto-immune haemolytic anaemia (AIHA is an acquired type of haemolytic anaemia, ca used by autoantibodies directed against the red cells. We hereby report a cross sectional study of chronic severe anaemia, which presented to our hospital for evaluation.5 patients o f the 36 patients evaluated over a period of 3 months were found to have a haemolytic anaemia.2 patients had beta thalassemia minor and 3 patients had autoimmune haemolytic anaemia with wa rm antibodies. Treatment with prednisolone resulted in significant improvement of t he haematological parameters in these 3 patients along with blood transfusion. Alternative a etiological causes of anaemia should be considered in patients with microcytic hypochromic an aemia for proper management of patients.

  3. Screening for thalassemia and other hemoglobinopathies in a tertiary care hospital of West Bengal: implications for population screening. (United States)

    Jain, Bhawna Bhutoria; Roy, Rabindra Nath; Ghosh, Sulekha; Ghosh, Tapan; Banerjee, Uma; Bhattacharya, Subodh Kumar


    Hemoglobinopathies are common genetic disorders of hemoglobin, which can be prevented by population screening and offering genetic counseling. In absence of population-based screening for hemoglobinopathies, the hospital-based diagnosis register provide idea about the extent of problem in the community. The present study was undertaken to find out the burden of hemoglobinopathies and spectrum of this disorders among the population who were screened in the hospital-based screening program. A record-basedanalysis of subjects who underwent screening for hemoglobinopathies in Burdwan Medical College and Hospital over a period of 3 years and 4 months revealed that overall 29.3% of subjects were positive for hemoglobinopathies. Beta thalassemia heterozygous was the most commonhemoglobinopathy in this region closely followed by hemoglobin E heterozygous. In view of high prevalence of hemoglobinopathies in this region, a routine premarital screening program is needed for identification and prevention of high-risk marriages.

  4. The role of ineffective erythropoiesis in non-transfusion-dependent thalassemia. (United States)

    Rivella, Stefano


    Ineffective erythropoiesis is the hallmark of beta-thalassemia that triggers a cascade of compensatory mechanisms resulting in clinical sequelae such as erythroid marrow expansion, extramedullary hematopoiesis, splenomegaly, and increased gastrointestinal iron absorption. Recent studies have begun to shed light on the complex molecular mechanisms underlying ineffective erythropoiesis and the associated compensatory pathways; this new understanding may lead to the development of novel therapies. Increased or excessive activation of the Jak2/STAT5 pathway promotes unnecessary disproportionate proliferation of erythroid progenitors, while other factors suppress serum hepcidin levels leading to dysregulation of iron metabolism. Preclinical studies suggest that Jak inhibitors, hepcidin agonists, and exogenous transferrin may help to restore normal erythropoiesis and iron metabolism and reduce splenomegaly; however, further research is needed.

  5. A case of plasmacytoma of scalp in pediatric thalassemia human immunodeficiency virus positive child

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    Swapan Kumar Mallick


    Full Text Available A 9-year-old female child, known case of beta thalassemia major and human immunodeficiency virus seropositive, presented with two slowly growing masses in the temporoparietal region of the skull on both sides. Irregular bony erosion at left parietal area with underlying scalp hematoma with similar change at the right side to a lesser degree were found. Fine needle aspiration cytology from masses showed abundant plasmacytoid cells some of which are binucleated along with free erythroblasts. Cytological features were suggestive of plasmacytoma. Serum protein electrophoresis showed no M-band. Urine was negative for Bence-Jones protein. Bone marrow biopsy showed no plasma cell neoplasm. Diagnosed as first reported case of primary multiple solitary plasmacyomas affecting bilateral temporoparietal bones in a pediatric patient, the child was treated with external beam radiation therapy to scalp lesions showing excellent results and on further follow-up showed no evidence of progressive disease.

  6. The diagnosis of microcytic anemia by a rule-based expert system using VP-Expert. (United States)

    O'Connor, M L; McKinney, T


    We describe our experience in creating a rule-based expert system for the interpretation of microcytic anemia using the expert system development tool, VP-Expert, running on an IBM personal computer. VP-Expert processes data (complete blood cell count results, age, and sex) according to a set of user-written logic rules (our program) to reach conclusions as to the following causes of microcytic anemia: alpha- and beta-thalassemia trait, iron deficiency, and anemia of chronic disease. Our expert system was tested using previously interpreted complete blood cell count data. In most instances, there was good agreement between the expert system and its pathologist-author, but many discrepancies were found in the interpretation of anemia of chronic disease. We conclude that VP-Expert has a useful level of power and flexibility, yet is simple enough that individuals with modest programming experience can create their own expert systems. Limitations of such expert systems are discussed.

  7. Effect of Combined versus Monotherapy with Deferoxamine and Deferiprone in Iron Overloaded Thalassemia Patients: a Randomized Clinical Trial

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    Sasan Hejazi


    Full Text Available Background: Patients with transfusional iron overload have depended on iron chelation therapy and improving chelation regimens have been of the highest priority. The aim of this study was to compare effect of combined versus monotherapy with Deferoxamine (DFO and Deferiprone (DFP in iron overloaded beta thalassemia (BT major patients Materials and Methods We studied 36 BT major patients (mean age 7.6±4.6; range 3–16 years attending the Ormieh Motahari hospital for regular transfusional support. Patients were randomly allocated to receive one of the following two treatments: DFO in combination with DFP (n=12, DFO alone (n=12 and DFP alone (n=12. Serum ferritin level, liver enzymes, blood urea nitrogen, and creatinine and side effects were monitored over a 12 months period. Results: After one year, serum ferritin decreased more significantly in patients on DFO+DFP therapy compared to patients who only received DFO or DFP alone (P

  8. Brazilian Thalassemia Association protocol for iron chelation therapy in patients under regular transfusion

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    Monica Pinheiro de Almeida Verissimo


    Full Text Available In the absence of an iron chelating agent, patients with beta-thalassemia on regular transfusions present complications of transfusion-related iron overload. Without iron chelation therapy, heart disease is the major cause of death; however, hepatic and endocrine complications also occur. Currently there are three iron chelating agents available for continuous use in patients with thalassemia on regular transfusions (desferrioxamine, deferiprone, and deferasirox providing good results in reducing cardiac, hepatic and endocrine toxicity. These practice guidelines, prepared by the Scientific Committee of Associação Brasileira de Thalassemia (ABRASTA, presents a review of the literature regarding iron overload assessment (by imaging and laboratory exams and the role of T2* magnetic resonance imaging (MRI to control iron overload and iron chelation therapy, with evidence-based recommendations for each clinical situation. Based on this review, the authors propose an iron chelation protocol for patients with thalassemia under regular transfusions.

  9. An isothermal primer extension method for whole genome amplification of fresh and degraded DNA: applications in comparative genomic hybridization, genotyping and mutation screening. (United States)

    Lee, Cheryl I P; Leong, Siew Hong; Png, Adrian E H; Choo, Keng Wah; Syn, Christopher; Lim, Dennis T H; Law, Hai Yang; Kon, Oi Lian


    We describe a protocol that uses a bioinformatically optimized primer in an isothermal whole genome amplification (WGA) reaction. Overnight incubation at 37 degrees C efficiently generates several hundred- to several thousand-fold increases in input DNA. The amplified product retains reasonably faithful quantitative representation of unamplified whole genomic DNA (gDNA). We provide protocols for applying this isothermal primer extension WGA protocol in three different techniques of genomic analysis: comparative genomic hybridization (CGH), genotyping at simple tandem repeat (STR) loci and screening for single base mutations in a common monogenic disorder, beta-thalassemia. gDNA extracted from formalin-fixed paraffin-embedded (FFPE) tissues can also be amplified with this protocol.

  10. Radiotherapy of paraplegias caused by extramedullar hemopoietic tissue

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    Dietz, R.; Niewald, M.; Schnabel, K.; Berberich, W.


    The presentation by computed tomography of an extramedullar epidural intraspinal hemopoisis has only been described sporadically. It has been possible to visualize by CT-scans the regression under radiotherapy of a sensory and motor paraplegia in a 17 years old patient with ..beta..-thalassemia major. The central nevous system (thoracic and lumbar zone as well as os sacrum) was exposed to a total reference dose of 30 Gy which was administered within twenty days by a /sup 60/Co unit in single doses of 2 Gy each. From 4 Gy on, the paraplegic symptoms regressed continuously. The control CT taken after 26 Gy - the paraplegia had completely disappeared as this time - showed a significant regression of the intraspinal soft tissue masses. Radiotherapy is very important in the treatment of this disease. A direct correlation is found between clinical symptoms and CT-presentation.

  11. Modulating the selectivity of matriptase-2 inhibitors with unnatural amino acids. (United States)

    St-Georges, Catherine; Désilets, Antoine; Béliveau, François; Ghinet, Mariana; Dion, Sébastien P; Colombo, Éloic; Boudreault, Pierre-Luc; Najmanovich, Rafael J; Leduc, Richard; Marsault, Éric


    Matriptase-2, a type II transmembrane serine protease (TTSP), is expressed in the liver and regulates iron homeostasis via the cleavage of hemojuvelin. Matriptase-2 emerges as an attractive target for the treatment of conditions associated with iron overload, such as hemochromatosis or beta-thalassemia. Starting from the crystal structure of its closest homolog matriptase, we constructed a homology model of matriptase-2 in order to further optimize the selectivity of serine trap peptidomimetic inhibitors for matriptase-2 vs matriptase. Careful modifications of the P4, P3 and P2 positions with the help of unnatural amino acids led to a thorough understanding of Structure-Activity Relationship and a >60-fold increase in selectivity for matriptase-2 vs matriptase. Additionally, the introduction of unnatural amino acids led to significant increases in plasma stability. Such compounds represent useful pharmacological tools to test matriptase-2 inhibition in a context of iron overload.

  12. Assessment of Iron Overload in Homozygous and Heterozygous Beta Thalassemic Children below 5 Years of Age

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    Dhiraj J. Trivedi


    Full Text Available Background: Thalassemia is a genetic disease having 3-7% carrier rate in Indians. It is transfusion dependent anemia having high risk of iron overloading. A clinical symptom of iron overload becomes detectable in second decade causing progressive liver, heart and endocrine glands damage. There is a need to assess iron overload in thalassemics below 5 years of age to protect them from complications at later age of life. Aims and objectives: Present study was undertaken to estimate serum iron status and evaluate serum transferrin saturation in both homozygous & heterozygous form of thalassemia as an index of iron overload among children of one to five years of age. Materials and Methods: Clinically diagnosed thirty cases of β thalassemia major & thirty cases of β thalassemia minor having severe anemia, hepatospleenomegaly and between 1 year to 5 years of age were included in study group and same age matched healthy controls were included in the study. RBC indices and HbA, HbA2 and HbF were estimated along with serum iron & serum Total Iron Binding Capacity (TIBC and serum transferrin levels. Results: Significant difference was observed in hemoglobin levels between control and both beta thalassemia groups. Mean Corpuscular Volume (MCV and Mean Corpuscular Hemoglobin (MCH values were reduced. Hemoglobin electrophoresis showed the elevated levels of HbF and HbA2 in both beta thalassemia groups. Among serum iron parameters, serum iron, TIBC and transferrin saturation were elevated whereas serum transferrin levels were low in thalassemia major in children below 5 years of age. Conclusion: Although clinical symptoms of iron overload have been absent in thalassemic children below five years of age, biochemical iron overloading has started at much lower age which is of great concern.

  13. Reversal of hemochromatosis by apotransferrin in non-transfused and transfused Hbbth3/+ (heterozygous B1/B2 globin gene deletion) mice. (United States)

    Gelderman, Monique P; Baek, Jin Hyen; Yalamanoglu, Ayla; Puglia, Michele; Vallelian, Florence; Burla, Bo; Vostal, Jaroslav; Schaer, Dominik J; Buehler, Paul W


    Intermediate beta-thalassemia has a broad spectrum of sequelae and affected subjects may require occasional blood transfusions over their lifetime to correct anemia. Iron overload in intermediate beta-thalassemia results from a paradoxical intestinal absorption, iron release from macrophages and hepatocytes, and sporadic transfusions. Pathological iron accumulation in parenchyma is caused by chronic exposure to non-transferrin bound iron in plasma. The iron scavenger and transport protein transferrin is a potential treatment being studied for correction of anemia. However, transferrin may also function to prevent or reduce iron loading of tissues when exposure to non-transferrin bound iron increases. Here we evaluate the effects of apotransferrin administration on tissue iron loading and early tissue pathology in non-transfused and transfused Hbb(th3/+) mice. Mice with the Hbb(th3/+) phenotype have mild to moderate anemia and consistent tissue iron accumulation in the spleen, liver, kidneys and myocardium. Chronic apotransferrin administration resulted in normalization of the anemia. Furthermore, it normalized tissue iron content in the liver, kidney and heart and attenuated early tissue changes in non-transfused Hbb(th3/+) mice. Apotransferrin treatment was also found to attenuate transfusion-mediated increases in plasma non-transferrin bound iron and associated excess tissue iron loading. These therapeutic effects were associated with normalization of transferrin saturation and suppressed plasma non-transferrin bound iron. Apotransferrin treatment modulated a fundamental iron regulatory pathway, as evidenced by decreased erythroid Fam132b gene (erythroferrone) expression, increased liver hepcidin gene expression and plasma hepcidin-25 levels and consequently reduced intestinal ferroportin-1 in apotransferrin-treated thalassemic mice.

  14. Reticulocyte parameters in hemoglobinopathies and iron deficiency anemia

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    Cortellazzi Laura C.


    Full Text Available Flow cytometric reticulocyte analysis allows the evaluation of reticulocyte maturity. New reticulocyte parameters have been used in the diagnosis and management of anemias, in the bone marrow transplant setting and in the monitoring of iron replacement or erythropoiet in therapy. Reticulocyte numbers and maturation levels have been studied in different hemoglobinopathies and the results have been correlated with the degree of ineffective erythropoiesis. In order to verify differences in reticulocyte parameters in various types of anemias and to test the absolute number of immature reticulocytes as a possible discriminating factor among various types of anemias, reticulocyte counts were performed on 219 samples from patients with sickle cell anemia (SS (n= 62, hemoglobin S trait (n=9, Sbeta thalassemia (n=7, hemoglobin SC disease (n=11, beta thalassemia trait (n=33 and iron deficiency anemia (n= 47, and non-anemic individuals (n= 50. Mean fluorescence index (MFI was defined as representative of the degree of reticulocyte immaturity and it was evaluated as a percentage and in absolute values. Reticulocyte counts and MFI values were significantly higher in SS, Sbeta thalassemic and SC groups when compared to controls, but not different among the three anemia groups. Patients with hemoglobin S trait, iron deficiency anemia and beta thalassemia trait showed reticulocyte parameters similar to the non-anemic group. There was no difference between the b thalassemic trait and iron deficiency anemia in relation to any parameters. MFI in absolute numbers were significantly higher in anemias that develop with the hemolytic process, although this was not evident in MFI percentage values. Our results showed that the erythoid expansion in sickle cell diseases (SS, SC and Sb thalassemia leads to an enhanced immature reticulocyte release from bone marrow and that the phenomena is more evident by the MFI counting in absolute figures than in percentages. We

  15. Detection of a major gene for heterocellular hereditary persistence of fetal hemoglobin after accounting for genetic modifiers

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    Thein, S.L.; Weatherall, D.J. (Institute of Molecular Medicine, Oxford (United Kingdom)); Sampietro, M.; Rohde, K.; Rochette, J.; Lathrop, G.M.; Demenais, F.


    [open quotes]Heterocellular hereditary persistence of fetal hemoglobin[close quotes] (HPFH) is the term used to describe the genetically determined persistence of fetal hemoglobin (Hb F) production into adult life, in the absence of any related hematological disorder. Whereas some forms are caused by mutations in the [beta]-globin gene cluster on chromosome 11, others segregate independently. While the latter are of particular interest with respect to the regulation of globin gene switching, it has not been possible to determine their chromosomal location, mainly because their mode of inheritance is not clear, but also because several other factors are known to modify Hb F production. The authors have examined a large Asian Indian pedigree which includes individuals with heterocellular HPFH associated with [beta]-thalassemia and/or [alpha]-thalassemia. Segregation analysis was conducted on the HPFH trait FC, defined to be the percentage of Hb F-containing cells (F-cells), using the class D regressive model. The results provide evidence for the presence of a major gene, dominant or codominant, which controls the FC values with residual familial correlations. The major gene was detected when the effects of genetic modifiers, notably [beta]-thalassemia and the XmnI-[sup G][gamma] polymorphism, are accounted for in this analysis. Linkage with the [beta]-globin gene cluster is excluded. The transmission of the FC values in this pedigree is informative enough to allow detection of linkage with an appropriate marker(s). The analytical approach outlined in this study, using simple regression to allow for genetic modifiers and thus allowing the mode of inheritance of a trait to be dissected out, may be useful as a model for segregation and linkage analyses of other complex phenotypes. 39 refs., 4 figs., 6 tabs.

  16. Molecular characterization of hemoglobin D Punjab traits and clinical-hematological profile of the patients

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    Sanjay Pandey

    Full Text Available CONTEXT AND OBJECTIVE: Hemoglobin (Hb D hemoglobinopathies are widespread diseases in northwestern India and usually present with mild hemolytic anemia and mild to moderate splenomegaly. The heterozygous form of Hb D is clinically silent, but coinheritance of Hb D with Hb S or beta-thalassemia produces clinically significant conditions like thalassemia intermedia of moderate severity. Under heterozygous conditions with coinheritance of alpha and beta-thalassemia, patients show a degree of clinical variability. Thus, our aim was to molecularly characterize the Hb D trait among individuals who were clinically symptomatic because of co-inheritance of alpha deletions or any beta-globin gene mutations. DESIGN AND SETTING: This was a cross-sectional study conducted in an autonomous tertiary-care hospital. METHODS: Complete blood count and red cell indices were measured using an automated cell analyzer. Quantitative assessment of hemoglobin Hb F, Hb A, Hb A2 and Hb D was performed by means of high performance liquid chromatography (HPLC. DNA extraction was done using the phenol-chloroform method. Molecular analyses on common alpha deletions and common beta mutations were done using the Gap polymerase chain reaction and Amplification Refractory Mutation System, respectively. RESULTS: We evaluated 30 patients and found clinical variation in the behavior of Hb D traits. In six patients, the Hb D traits were clinically symptomatic and behaved like those of thalassemia intermedia. Molecular characterization showed that three out of these six were IVS-1-5 positive. CONCLUSIONS: HPLC may not be the gold standard for diagnosing symptomatic Hb D Punjab traits. Hence, standard confirmation should include molecular studies.

  17. The organization of the gamma-delta-beta gene complex in normal and thalassemia cells. (United States)

    Bank, A; Mears, J G; Ramirez, F; Burns, A L; Spence, S; Feldenzer, J; Baird, M


    Restriction enzyme digestion analysis and direct human globin gene cloning have permitted analysis of the physical arrangement of nucleotide sequences within and surrounding the human globin genes. With these methods it has been shown that the linear arrangement 5' to 3' of the globin genes is G gamma-A gamma-delta-beta. The G gamma and A gamma genes are separated by about 3.5 kilobases (kb), while the A gamma and delta genes are 15 kb apart, and the delta and beta 6.5 kb apart. Each of these genes contains a large intervening sequence (IVS) of approximately 1 kb in precisely the same position between condons 104 and 105. In addition, each of these genes has a small IVS between codons 30 and 31. In homozygous delta beta thalassemia DNA, there is deletion of all of the normal delta and beta gene fragments. However, a new fragment 4.2 kb in size containing the 5' end of the delta globin gene is retained. Retention of this fragment in delta beta thalassemia, but not in HPFH is consistent with a role for sequences in this region for limiting gamma globin gene expression. Studies to date suggest that the beta + and beta 0 thalassemias will be due to a heterogeneous group of DNA defects affecting either beta globin gene transcription or beta mRNA processing. In most cases of beta + and beta 0 thalassemia DNA analyzed, there is no detectable deletion of beta or delta genes. In three India beta 0 patients, deletion of the 3' end of the beta gene has been found. Analysis of cloned beta globin genes from a patient with beta + thalasseia shows differences from normal in the fragments generated by restriction enzymes which cut frequently. Whether these differences are responsible for the defect in thalassemia or are polymorphisms unrelated to thalassemia remains to be determined.

  18. Síndrome de Plummer-Vinson: uma rara associação na talassemia Plumer-Vinson syndrome: a rare association with thalassemia

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    Eduardo Crema


    Full Text Available A síndrome de Plummer-Vinson é caracterizada por disfagia cervical, deficiência de ferro e presença de membrana esofágica. Neste estudo, relatam-se dois casos dessa síndrome em irmãos adolescentes. Eles não obtiveram aumento dos níveis hematimétricos após reposição com ferro oral, o que, associado à eletroforese de hemoglobinas, sustentou o diagnóstico de talassemia concomitante. Devido ao quadro dos filhos, os pais foram também submetidos à eletroforese de hemoglobinas cujo diagnóstico do pai foi talassemia alfa/beta menor e da mãe, talassemia alfa menor. Os irmãos tiveram disfagia refratária e necessitaram de dilatação endoscópica. Ambos necessitaram de terapia com ferro venoso com melhora dos níveis hematimétricos.Plummer-Vinson syndrome is characterized by cervical dysphagia, iron deficiency and the presence of esophageal membranes. We report two cases of this syndrome present in adolescent brothers with associated thalassemia. After oral iron therapy, their hematimetric levels showed no increase, which associated with the results of hemoglobin electrophoresis, sustained the diagnosis of thalassemia. Due to the condition of the children, the parents were submitted to hemoglobin electrophoresis examinations; the father was diagnosed as having minor alpha/beta thalassemia and the mother as minor beta thalassemia. Both patients suffered from refractory dysphagia and required endoscopic dilatation. They both underwent venous iron therapy, which improved the hematimetric levels.

  19. Prevalence of thalassemia and hemoglobinopathy in eastern India: A 10-year high-performance liquid chromatography study of 119,336 cases

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    Santosh Kumar Mondal


    Full Text Available Background: Hereditary hemoglobin (Hb disorders are the most commonly encountered single gene disorders in India. Proper timely identification of these disorders is of paramount importance to prevent thalassemia major and clinically severe hemoglobinopathy as well as for epidemiologic purposes. Aims: Our aim was to determine the prevalence of thalassemia and hemoglobinopathy in patients of a tertiary care hospital of West Bengal, India. Materials and Methods: This prospective study was conducted on 119,336 cases over a period of 10 years. After taking clinical history and familial history, complete hemogram report was obtained by an automated cell counter. High-performance liquid chromatography (HPLC was performed on the samples with Bio-Rad Variant using beta thalassemia short program. Confirmatory tests were performed whenever required. Results: A normal Hb pattern was observed in 104,804 (87.83% cases and abnormalities were detected in 14,532 (12.17% patients. β (beta thalassemia trait was the commonest abnormality found in 5,488 (4.60% patients. HbE trait was found in 3,604 (3.02% patients, β thalassemia major/intermedia in 1,981 (1.66% cases, and Eβ thalassemia in 1,384 (1.16 % cases. Other variants detected included HbE disease, sickle-cell disease, sickle β thalassemia, HbD-Punjab trait, HbQ-India trait, α-thal trait, double heterozygous state of HbS and HbE, double heterozygous state of HbS and HbD, HbJ-Meerut, hereditary persistence of fetal hemoglobin (HPFH, HbH, delta β-thal trait, and Hb Lepore. Conclusion: In view of the high prevalence of hemoglobinopathy in this region, a routine premarital screening program is needed for the identification and prevention of high-risk marriages and thus, prevention of the psychosocial trauma of bearing a transfusion-dependent child for life.

  20. Suicide for survival--death of infected erythrocytes as a host mechanism to survive malaria. (United States)

    Föller, Michael; Bobbala, Diwakar; Koka, Saisudha; Huber, Stephan M; Gulbins, Erich; Lang, Florian


    The pathogen of malaria, Plasmodium, enters erythrocytes and thus escapes recognition by the immune system. The pathogen induces oxidative stress to the host erythrocyte, which triggers eryptosis, the suicidal death of erythrocytes. Eryptosis is characterized by cell shrinkage, membrane blebbing and cell membrane phospholipid scrambling with phosphatidylserine exposure at the cell surface. Phosphatidylserine-exposing erythrocytes are identified by macrophages which engulf and degrade the eryptotic cells. To the extent that infected erythrocytes undergo eryptosis prior to exit of Plasmodiaand subsequent infection of other erythrocytes, the premature eryptosis may protect against malaria. Accordingly, any therapeutical intervention accelerating suicidal death of infected erythrocytes has the potential to foster elimination of infected erythrocytes, delay the development of parasitemia and favorably influence the course of malaria. Eryptosis is stimulated by a wide variety of triggers including osmotic shock, oxidative stress, energy depletion and a wide variety of xenobiotics. Diseases associated with accelerated eryptosis include sepsis, haemolytic uremic syndrome, malaria, sickle-cell anemia, beta-thalassemia, glucose-6-phosphate dehydrogenase (G6PD)-deficiency, phosphate depletion, iron deficiency and Wilson's disease. Among the known stimulators of eryptosis, paclitaxel, chlorpromazine, cyclosporine, curcumin, PGE2 and lead have indeed been shown to favourably influence the course of malaria. Moreover, sickle-cell trait, beta-thalassemia trait, glucose-6-phosphate dehydrogenase (G6PD)-deficiency and iron deficiency confer some protection against a severe course of malaria. Importantly, counteracting Plasmodia by inducing eryptosis is not expected to generate resistance of the pathogen, as the proteins involved in suicidal death of the host cell are not encoded by the pathogen and thus cannot be modified by mutations of its genes.

  1. 地中海贫血基因诊断在优生优育中的应用%Application of the eugenics in the gene diagnosis of thalassemia

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    王志剑; 邓之敏; 邝永辉


    目的:探讨河源地区地中海贫血的发病情况及基因分型。为开展地中海贫血的遗传咨询、产前诊断和预防计划提供参考。方法用一管定量法红细胞渗透脆性检测筛检受检人员,对筛查阳性或阴性临床疑似病例及部分贫血查因病例进行地贫基因检测。结果在7872例受检者,筛查出阳性272例,发生率为3.5%;对筛查部分阳性和阴性临床疑似病例及部分贫血查因病例标本132例进行地中海贫血基因检测,其中α地中海贫血48例(36.4%),β地中海贫血45例(34.1%),α、β混合型地中海贫血6例(4.5%),非地中海贫血33例(25%)。基因诊断为地中海贫血患者中(99例)筛查为阴性者19例,漏诊率为19.1%结论河源地区人口中的α与β地中海贫血的基因突变类型和频率较高,婚前检查、孕检或产前诊断应以地中海贫血基因诊断为主,为遗传咨询提供了理论依据,减少本地区地中海贫血的发生率。%Objective The incidence of thalassemia in Heyuan and studying gene typing. To provide reference for genetic counseling, prenatal diagnosis of Mediterranean anemia and prevention program. Methods Using a quantita-tive method erythrocyte osmotic fragility test screening inspection personnel, to screen the positive or negative clinical sus-pected cases and anemia were thalassemia gene detection check. Results in 7 872 examined cases, screening out the positive in 272 cases, the positive rate was 3.5%; Screening for part of the positive and negative clinical suspected cases and anemia check cases specimens from 132 patients were thalassemia gene detection, including 48 cases of alpha tha-lassemia (36.4%), 45 patients with beta thalassemia (34.1%), 6 cases of alpha, beta thalassemia mixed type (4.5%), 33 cas-es (25%) of non thalassemia. gene diagnosis for thalassemia patients (99 cases) screening was negative in 19 cases, the missed diagnosis rate was 19

  2. Densidade mineral óssea em crianças talassêmicas: uma experiência brasileira Bone mineral density in thalassemic children: a Brazilian experience

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    Perla Vicari


    Full Text Available A osteoporose, caracterizada por aumento da fragilidade óssea e suscetibilidade a fraturas, é inversamente proporcional ao pico de massa óssea adquirido na infância. Por outro lado, a doença óssea é uma importante causa de morbidade em pacientes portadores de beta-talassemia maior (TM. Apesar de intensamente descrita em pacientes talassêmicos adultos, não existem estudos sobre as alterações de densidade óssea em crianças talassêmicas brasileiras. Foram avaliados 11 pacientes (idade mediana de 10,0, variando de 5 a 12 anos, portadores de TM, e 24 crianças (idade mediana de 9,5, variando de 6 a 12 anos saudáveis, utilizando medida de emissão dupla de raios-X para avaliar a densidade mineral óssea (DMO. A análise de marcadores bioquímicos tais como concentração de ferritina sérica, cálcio ionizado, fosfatase alcalina, fósforo, albumina, tempo de protrombina e fator V foi realizada. A estatura foi significativamente diferente entre os dois grupos estudados, pOsteoporosis is characterized by low bone mass and disruption of bone architecture, resulting in greater bone fragility with increased risk of fractures. Bone disease is an important cause of morbidity in beta thalassemia major patients. Osteoporosis has been described extensively in adult thalassemia. However, there are no studies describing Brazilian thalassemic children. We evaluated eleven patients with beta thalassemia major (median age of 10.0 years, range from 5 to 12 years and twenty-four healthy children (median age of 9.5 years, range from 6 to 12 years, using dual X-ray absorptiometry to assess bone mineral density (BMD. Analysis of biochemical markers such as serum ferritin concentration, ionized calcium, alkaline phosphatase, phosphorus, albumin, prothrombin time and factor V was performed. The height was very different between the groups, p<0.05. The thalassemic patients showed significantly lower BMD (median 0.61 g/cm² than control subjects (median 0.69 g

  3. Evaluation of Endocrine Complications in Patients with Thalassemia Major

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    Birol Baytan


    Full Text Available Aim: Multiple blood transfusions in beta thalassemia patients causes iron overload in various tissues including endocrine glands thereby leading to multiple endocrine dysfunction. The aim of this study was to determine the endocrine complications seen in beta thalassemia patients followed-up in outpatient clinics of Pediatric Hematology Division of Uludag University Faculty of Medicine. Materials and Methods: The files of patients with thalassemia major followed-up in outpatient clinics of Pediatric Hematology Division of Uludag University Faculty of Medicine from January 1976 to August 2008 were retrospectively evaluated for endocrine disorders. All patients had a detailed physical examination including palpation of thyroid gland and pubertal staging. Endocrine evaluation was performed in the Division of Pediatric Endocrinology.Results: A total of 44 [20 female (45.5%; 24 male (54.5%; and mean chronological age 13.54±7.32 (2.75-35.2 years] patients were evaluated. The ratios of patients with endocrine dysfunction were 27.2 % and 90.9%, respectively, when we exclude or include those with osteoporosis/osteopenia or growth failure other than growth hormone deficiency. Of all patients, 27 (61.3% had osteoporosis, 17 (38.6% had growth retardation, 11 (25% had osteopenia, 6 (13.6% had hypogonadism, 3 (6.8% had hypothyroidism, 2 (4.5% had hypoparathyroidism, 1 (2.3 had growth hormone deficiency, and 1 (2.3 had type 1 diabetes mellitus. Mean ferritin levels and monthly transfusion numbers were 1976.15±1494.75 ng/ml and 1.46±0.34, respectively. There were no significant association between ferritin levels, monthly transfusion needs, and endocrine dysfunctions studied. Endocrine dysfunctions did not differ significantly amongst those having different chelating agents. The ratio of patients with growth retardations in 10 to 19-age-group was significantly higher than those in 0 to 9-age-group (30.6% vs 8.3%; p=0.049. Conclusion: Patients with

  4. Serological study on parvovirus B19 infection in multitransfused thalassemia major patients and its transmission through donor units

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    Kishore Janak


    Full Text Available Background: Human parvovirus B19 (B19 virus is a newly recognized agent for transfusion transmitted diseases. Beta-thalassemia major patients receive a hypertransfusion regimen, hence, are prone to acquire B19 infection; moreover, B19 escapes viral inactivation methods and donor units are not tested for B19, but there are just a couple of studies globally and none from the Asian continent. Hence, a study was designed to find the frequency of B19 infection and its transmission in multitransfused thalassemia patients. Materials and Methods: Ninety multitransfused beta-thalassemia major (thalassemia patients, 32 controls (age, sex matched without any history of transfusion were enrolled. Besides the donor units were tested in B19 un-infected patients. B19 specific IgG and IgM antibodies in the sera were analyzed by ELISA (in-house, using B19 VPI and VP2 recombinant and purified antigens; additionally HBsAg and anti-HIV and anti-HCV antibodies were tested for coexisting infections. Results: Seventy-three (81% thalassemia patients tested positive for anti-B19 IgG antibodies as compared to seven (21% in the controls group (P < 0.01, while anti-B19 IgM antibodies were detected in 37 (41.1% compared to two (6.2% in the controls (P < 0.01. Mean age of the thalassemia patient was eight years (range 2 - 18 years and B19 infection was highest in the six-to-ten year range. Seropositivity increased with the number of transfusions. Two of the four HBsAg positive and five of the seven anti-HCV IgM antibody-positive patients also had anti-B19 IgM. After a six-month follow-up, four (25% of the 16 seronegative patients seroconverted and anti-B19 IgM antibodies were detected in their donor units. Conclusions: Most of multitransfused thalassemics were B19 seropositive or had anti-B19 IgM; in the remaining uninfected group, B19 got transmitted through infected / IgM-positive donor units.

  5. Intervention and Prevention of Hereditary Hemolytic Disorders in Two Ethnic Communities of Sundargarh District of Orissa, India: An Experience from KAP Studies

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    Balgir RS


    Full Text Available Hereditary hemolytic disorders are important public health challenges in India. They cause a high degree of morbidity, mortality and fetal wastage in vulnerable communities. Tradition-bound-psychosocial influences are detrimental to the process of prevention. This study was designed to create awareness, motivate, and sensitize two major vulnerable tribal communities: Bhuyan and Kharia for hemoglobin and allied hemolytic disorders in addition to imparting prospective and retrospective genetic/marriage counseling. Bhuyan and Kharia tribal people in Orissa live in clusters practicing inter-village tribal endogamy and clan exogamy. For the present study, random sampling procedure for the selection of whole village was followed. Imparting of education, motivation and sensitization for carrier detection were carried out through IEC materials, holding interactive meetings and discussions at district, block and village levels. Both prospective and retrospective intervention and genetic/marriage counseling was done through the local PHC doctor. The pre- and post-intervention knowledge, attitude and practice (KAP studies were conducted. Tribal people were not knowing the signs and symptoms of sickle cell disease (2.1% and beta-thalassemia (1.0%, but after IEC, their knowledge was considerably improved (67.8%, 56.4%, respectively. Sickle cell patient needs treatment (37.6% like folic acid, blood transfusion, etc. Beta-thalassemia is disease causes bloodlessness and is a transfusion dependent (73.2%. All patients of thalassemia major or sickle cell disease have carrier parents and carriers do not suffer from any clinical ailments. After intervention, it was known that G-6-PD is an enzyme, which helps in glucose metabolism of red cells (76.4% and its hereditary deficiency causes hemolytic anemia, jaundice and black urination (73.8% in malaria cases when anti-malarials are administered. Methodical and prudent intervention and preventive strategies found

  6. AB063. Prevalence of thalassemias and hemoglobinopathies detected via high performance liquid chromatography in Filipinos (United States)

    Silao, Catherine Lynn; Fabella, Terence Diane; Yuson, Ernesto; Naranjo, Maria Liza; Padilla, Carmencita


    Background The thalassemias and hemoglobinopathies are groups of autosomal recessive inherited blood disorders affecting the quantity and quality of hemoglobin. Patients with the disease can vary from clinically asymptomatic to transfusion dependent individuals. It is considered prevalent in many parts of the world particularly in Southeast Asia. Thus, screening and prevalence determination of these diseases are important in the Filipino population. The study aims to determine the prevalence of thalassemias and hemoglobinopathies in the Philippines using high performance liquid chromatography. Methods Referred patients by hematologists from different parts of the country from October 2008 to December 2014 were included. Peripheral blood extracted from the subjects, were hemolyzed and screened for thalassemias and hemoglobinopathies using VariantTM HPLC. Data interpretations were based on levels of the HbA2 Fetal Hb and HbA detected. Results Majority of the patients were beta thalassemics followed by alpha-thalassemics. Hemoglobin E was found in 1% of the population tested while 2% of the patients have beta thalassemia with HbE interaction. Conclusions A significant proportion of thalassemias and hemoglobinopathies were determined from the 6-year screening of Filipinos using VariantTM HPLC. The results of this study provide not only confirmation of the occurrence and prevalence of these growing and diverse groups of genetic blood diseases but also suggest that the use of HPLC is a useful screening tool.

  7. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies (United States)

    Chandrashekar, Vani


    Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman's rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders. PMID:26989559

  8. Ethical issues of unrelated hematopoietic stem cell transplantation in adult thalassemia patients

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    Piras Eugenia


    Full Text Available Abstract Background Beta thalassemia major is a severe inherited form of hemolytic anemia that results from ineffective erythropoiesis. Allogenic hematopoietic stem cell transplantation (HSCT remains the only potentially curative therapy. Unfortunately, the subgroup of adult thalassemia patients with hepatomegaly, portal fibrosis and a history of irregular iron chelation have an elevated risk for transplantation-related mortality that is currently estimated to be about 29 percent. Discussion Thalassemia patients may be faced with a difficult choice: they can either continue conventional transfusion and iron chelation therapy or accept the high mortality risk of HSCT in the hope of obtaining complete recovery. Throughout the decision making process, every effort should be made to sustain and enhance autonomous choice. The concept of conscious consent becomes particularly important. The patient must be made fully aware of the favourable and adverse outcomes of HSCT. Although it is the physician's duty to illustrate the possibility of completely restoring health, considerable emphasis should be put on the adverse effects of the procedure. The physician also needs to decide whether the patient is eligible for HSCT according to the "rule of descending order". The patient must be given full details on self-care and fundamental lifestyle changes and be fully aware that he/she will be partly responsible for the outcome. Summary Only if all the aforesaid conditions are satisfied can it be considered reasonable to propose unrelated HSCT as a potential cure for high risk thalassemia patients.

  9. The Italian National External Quality Assessment Program in Molecular Genetic Testing: Results of the VII Round (2010-2011

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    F. Censi


    Full Text Available Since 2001 the Istituto Superiore di Sanità established a quality assurance programme for molecular genetic testing that covers four pathologies: Cystic Fibrosis (CF, Beta Thalassemia (BT, Fragile X Syndrome (FX, and Familial Adenomatous Polyposis Coli (APC. Since 2009 this activity is an institutional activity and participation is open to both public and private laboratories. Seven rounds have been performed until now and the eighth is in progress. Laboratories receive 4 DNA samples with mock clinical indications. They analyze the samples using their routine procedures. A panel of assessors review the raw data and the reports; all data are managed through a web utility. In 2010 the number of participants was 43, 17, 15, 5 for CF, BT, FX, APC schemes respectively. Genotyping results were correct in 96%, 98.5%, 100%, and 100% of CF, BT, FX, and APC samples, respectively. Interpretation was correct in 74%, 91%, 88%, and 60% of CF, BT, FX, and APC reports, respectively; however in most of them it was not complete but a referral to genetic counseling was given. Reports were satisfactory in more than 60% of samples in all schemes. This work presents the 2010 results in detail comparing our data with those from other European schemes.

  10. The importance of studying inherited hematological disorders in ancient Anatolian populations

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    Yeşim Doğan Alakoç


    Full Text Available Before analysis of DNA from ancient remains was possible, anthropologists studied evolution and migration patterns using data obtained from population genetic studies on modern populations combined with data obtained from morphological evaluations of ancient remains. Currently, DNA analysis of ancient populations is making a valuable contribution to these efforts. Researchers that perform ancient DNA analysis prefer to study polymorphisms on the Y chromosome or mitochondrial DNA because the results are easier to statistically evaluate. To evaluate polymorphisms on diploid genomes, which are more informative, only mutations that have been extensively examined in modern populations should be chosen. The most extensively evaluated mutations are those related to prevalent inherited disorders. As such, beta-thalassemia, sickle cell anemia, FVL mutation of globin and the factor V genes are good candidates for DNA studies in ancient populations. These mutations are common in Anatolia, host to many civilizations since the Paleolithic period. This history makes Anatolia a good place for conducting research that could enhance our understanding of human evolution and migration patterns.

  11. Acute Sickle Hepatic Crisis after Liver Transplantation in a Patient with Hb SC Disease

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    J. H. Gillis


    Full Text Available Acute sickle hepatic crisis (ASHC has been observed in approximately 10% of patients with sickle cell disease. It occurs predominantly in patients with homozygous (Hb SS sickle cell anemia and to a lesser degree in patients with Hb SC disease, sickle cell trait, and Hb S beta thalassemia. Patients commonly present with jaundice, right upper quadrant pain, nausea, low-grade fever, tender hepatomegaly, and mild to moderate elevations in serum AST, ALT, and bilirubin. We describe the case of a patient with a history of hemoglobin SC disease and cirrhosis caused by hepatitis C presenting approximately 1 year after liver transplantation with an ASHC. The diagnosis was confirmed by liver biopsy. Our patient was treated with RBC exchange transfusions, IV hydration, and analgesia and made a complete recovery. Only a limited number of patients with sickle cell disease have received liver transplants, and, to our knowledge, this is the first case of ASHC after transplantation in a patient with Hb SC disease.

  12. Seroprevalence of Hepatitis B, Hepatitis C and HIV in Patients with Hemoglobinopathy Patients

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    Gul ilhan


    Full Text Available Purpose: Thalassemia and sickle cell anemia patients have frequent transfusions. Hepatitis B (HBV, hepatitis C (HCV and human immunodeficiency virus (HIV are tramsmitted infections with blood. The objective of this study is to determine frequency of these infections in our hemoglobinopathy patients. Material and Methods: We investigated 410 hemoglobinopathy patients. Viral serologies were detected with second-generation enzyme-linked immunosorbent assay method. In 410 patients (116 thalassemia major, 16 thalassemia intermedia, 12 hemoglobin H, 222 sickle cell anemia, 43 sickle-beta thalassemia and 1 Hb SE, there were 258 males and 152 females. Results: The rate of HBV is 1,2%, HCV is 3,2% and HIV is 0%. Our results shows that transfusion transmitted viral infection prevelance is not high compared to the literature. Conclusion: Using sensitive screening tests with periodically and right donor selection are very important for preventing these infections in hemoglobinopathy patients who are under high risk. [Cukurova Med J 2014; 39(4.000: 784-787

  13. Advances in stem cell transplantation and gene therapy in the β-hemoglobinopathies. (United States)

    Payen, Emmanuel; Leboulch, Philippe


    High-level production of β-globin, γ-globin, or therapeutic mutant globins in the RBC lineage by hematopoietic stem cell gene therapy ameliorates or cures the hemoglobinopathies sickle cell disease and beta thalassemia, which are major causes of morbidity and mortality worldwide. Considerable efforts have been made in the last 2 decades in devising suitable gene-transfer vectors and protocols to achieve this goal. Five years ago, the first β(E)/β(0)-thalassemia major (transfusion-dependent) patient was treated by globin lentiviral gene therapy without injection of backup cells. This patient has become completely transfusion independent for the past 4 years and has global amelioration of the thalassemic phenotype. Partial clonal dominance for an intragenic site (HMGA2) of chromosomal integration of the vector was observed in this patient without a loss of hematopoietic homeostasis. Other patients are now receiving transplantations while researchers are carefully weighing the benefit/risk ratio and continuing the development of further modified vectors and protocols to improve outcomes further with respect to safety and efficacy.

  14. Molecular basis of inherited microcytic anemia due to defects in iron acquisition or heme synthesis. (United States)

    Iolascon, Achille; De Falco, Luigia; Beaumont, Carole


    Microcytic anemia is the most commonly encountered anemia in general medical practice. Nutritional iron deficiency and beta thalassemia trait are the primary causes in pediatrics, whereas bleeding disorders and anemia of chronic disease are common in adulthood. Microcytic hypochromic anemia can result from a defect in globin genes, in heme synthesis, in iron availability or in iron acquisition by the erythroid precursors. These microcytic anemia can be sideroblastic or not, a trait which reflects the implications of different gene abnormalities. Iron is a trace element that may act as a redox component and therefore is integral to vital biological processes that require the transfer of electrons as in oxygen transport, oxidative phosphorylation, DNA biosynthesis and xenobiotic metabolism. However, it can also be pro-oxidant and to avoid its toxicity, iron metabolism is strictly controlled and failure of these control systems could induce iron overload or iron deficient anemia. During the past few years, several new discoveries mostly arising from human patients or mouse models have highlighted the implication of iron metabolism components in hereditary microcytic anemia, from intestinal absorption to its final inclusion into heme. In this paper we will review the new information available on the iron acquisition pathway by developing erythrocytes and its regulation, and we will consider only inherited microcytosis due to heme synthesis or to iron metabolism defects. This information could be useful in the diagnosis and classification of these microcytic anemias.

  15. The profile of free amino acids in latent fingerprint of healthy and beta-thalassemic volunteers. (United States)

    Khedr, Alaa


    The aim of the present work is to apply a non-invasive test, using thumb fingerprint residue analysis, for detection of beta-thalassemia (beta-Thal). The relative percentages of free amino acids (AA) in the latent fingerprint of beta-Thal patients and healthy subjects were compared. The sample included 24 beta-Thal patient and 24 healthy subjects, aged 5-10 years old. Twenty-three AA plus ammonia were analyzed by a sensitive high-performance liquid chromatographic method with fluorescence detection. The profile of AA was calculated based on the percentage of relative amount of each AA to serine (Ser) as it found to be the predominant peak. The statistical and chromatographic profiles of beta-Thal patients were characterized by significant decrease of ornithine, lysine, and zero tyrosine, with significant increase of ammonia, and proline. Other amino acids that exist in low ratios were estimated statistically for significance changes. The relative percentages of each AA of healthy subjects were approximately constant. For this reason, these mentioned AA were assigned as major fingerprint markers of beta-Thal.

  16. RDW as differential parameter between microcytic anemias in "pure" and concomitant forms

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    Januária F. Matos


    Full Text Available Introduction: Iron deficiency anemia and thalassemia minor are microcytic and hypochromic types of anemia commonly found in our environment. The correct differentiation between them is of great clinical importance, although it is often hampered by the coexistence of diseases that may alter the results of standard tests for their discrimination, in addition to the significant costs of such tests. Objective: The objective of this study was to investigate the discriminatory power of red cell distribution width (RDW between iron deficiency anemia and thalassemia minor. Method: Blood parameters were compared in 227 patients with iron deficiency anemia and/or thalassemia minor after diagnosis confirmed by molecular biology and HbA2 measurement for alpha thalassemia and beta thalassemia trait respectively. The frequency of alpha thalassemia trait in a population from two public hospitals of Minas Gerais was also determined. Result and conclusion: RDW was able to differentiate iron deficiency anemia from thalassemia trait, what indicates that this blood count parameter is a useful tool since concomitant disorders are excluded. In addition, a high frequency of the -α3.7 mutation was observed in the study population (20.3%, justifying its investigation when another cause for microcytic anemia is absent.

  17. Molecular Mechanism of AHSP-Mediated Stabilization of Alpha-Hemoglobin

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    Feng,L.; Gell, D.; Zhou, S.; Gu, L.; Kong, Y.; Li, J.; Hu, M.; Yan, N.; Lee, C.; et al.


    Hemoglobin A (HbA), the oxygen delivery system in humans, comprises two alpha and two beta subunits. Free alpha-hemoglobin (alphaHb) is unstable, and its precipitation contributes to the pathophysiology of beta thalassemia. In erythrocytes, the alpha-hemoglobin stabilizing protein (AHSP) binds alphaHb and inhibits its precipitation. The crystal structure of AHSP bound to Fe(II)-alphaHb reveals that AHSP specifically recognizes the G and H helices of alphaHb through a hydrophobic interface that largely recapitulates the alpha1-beta1 interface of hemoglobin. The AHSP-alphaHb interactions are extensive but suboptimal, explaining why beta-hemoglobin can competitively displace AHSP to form HbA. Remarkably, the Fe(II)-heme group in AHSP bound alphaHb is coordinated by the distal but not the proximal histidine. Importantly, binding to AHSP facilitates the conversion of oxy-alphaHb to a deoxygenated, oxidized [Fe(III)], nonreactive form in which all six coordinate positions are occupied. These observations reveal the molecular mechanisms by which AHSP stabilizes free alphaHb.

  18. [Acute encephalic manifestations in Senegalese children with sickle cell disease]. (United States)

    Diagne, I; Diagne-Guèye, N R; Fall, L; Ndiaye, O; Camara, B; Diouf, S; Signate-Sy, H; Kuakuvi, N


    The course of sickle cell disease (SCD) may be complicated by neurologic events, mainly bactérial meningitidis and stroke. We retrospectively studied all cases with acute encephalic manifestations (AEM) in a cohort of 461 children and adolescents with SCD followed at Albert Royer Children Hospital of Dakar (Senegal) from january 1991 to december 2000 (ten years). Among them 438 had sickle cell anemia (SCA), 19 SC disease and 4 S-beta thalassemia (3 S-beta+, 1 S-beta0). Seven patients, all with SCA, presented antecedents of AEM revealed by flacid and proportionnal hemiplegia evoking stroke. Prevalence of these AEM was 1.5 per cent among patients with SCD and 1.6 per cent among those with SCA. They were 4 girls and 3 boys (sex ratio = 0.75) aged 4 to 8.5 years when occurred the first accident. We observed no clinical or biological distinctive characteristic of SCA in these patients compared to those without crebrovascular accident. Recurrence was observed once in a boy after a 12 months interval and twice in a girl after 20 and 60 months intervals successively. No transfusionnal program was applied to prevent recurrent stroke because of insufficient conditions for long-term transfusion. Stroke appears to be rare in senegalese children with SCD. However it poses in our context the major problem of applicability of transfusionnal program which constitute the only therapy universally recognised to be effective to prevent recurrence. Nevertheless hydroxyurea could be a satisfactory alternative.

  19. Congenital erythropoietic porphyria due to a mutation in GATA1: the first trans-acting mutation causative for a human porphyria. (United States)

    Phillips, John D; Steensma, David P; Pulsipher, Michael A; Spangrude, Gerald J; Kushner, James P


    Congenital erythropoietic porphyria (CEP), an autosomal recessive disorder, is due to mutations of uroporphyrinogen III synthase (UROS). Deficiency of UROS results in excess uroporphyrin I, which causes photosensitization. We evaluated a 3-year-old boy with CEP. A hypochromic, microcytic anemia was present from birth, and platelet counts averaged 70 x 10(9)/L (70,000/microL). Erythrocyte UROS activity was 21% of controls. Red cell morphology and globin chain labeling studies were compatible with beta-thalassemia. Hb electrophoresis revealed 36.3% A, 2.4% A(2), 59.5% F, and 1.8% of an unidentified peak. No UROS or alpha- and beta-globin mutations were found in the child or the parents. The molecular basis of the phenotype proved to be a mutation of GATA1, an X-linked transcription factor common to globin genes and heme biosynthetic enzymes in erythrocytes. A mutation at codon 216 in the child and on one allele of his mother changed arginine to tryptophan (R216W). This is the first report of a human porphyria due to a mutation in a trans-acting factor and the first association of CEP with thalassemia and thrombocytopenia. The Hb F level of 59.5% suggests a role for GATA-1 in globin switching. A bone marrow allograft corrected both the porphyria and the thalassemia.

  20. Hb A1c Separation by High Performance Liquid Chromatography in Hemoglobinopathies

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    Vani Chandrashekar


    Full Text Available Hb A1c measurement is subject to interference by hemoglobin traits and this is dependent on the method used for determination. In this paper we studied the difference between Hb A1c measured by HPLC in hemoglobin traits and normal chromatograms. We also studied the correlation of Hb A1c with age. Hemoglobin analysis was carried out by high performance liquid chromatography. Spearman’s rank correlation was used to study correlation between A1c levels and age. Mann-Whitney U test was used to study the difference in Hb A1c between patients with normal hemoglobin and hemoglobin traits. A total of 431 patients were studied. There was positive correlation with age in patients with normal chromatograms only. No correlation was seen in Hb E trait or beta thalassemia trait. No significant difference in Hb A1c of patients with normal chromatograms and patients with hemoglobin traits was seen. There is no interference by abnormal hemoglobin in the detection of A1c by high performance liquid chromatography. This method cannot be used for detection of A1c in compound heterozygous and homozygous disorders.

  1. Evaluation of Iron Deposition in the Adrenal Glands of β Thalassemia Major Patients Using 3-Tesla MRI

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    Full Text Available Background Beta-thalassemia major (β-TM patients need blood transfusions, which result in iron deposition. To regulate chelation therapy, iron load has to be measured. With MRI, the amount of signal loss and T2* decay time shortening are used for iron quantification. Objectives The aim was to measure adrenal iron load with T2* relaxometry using MRI, and to compare it with liver and cardiac iron and serum ferritin, and to find out whether adrenal iron could be predicted from those parameters. Patients and Methods Between October 2014 and March 2015, MRI was performed in 21 patients with β-TM, recieving blood transfusions and chelation therapy. The control group (n = 11 included healthy volunteers with no known history of adrenal, hematologic, chronic disease, and blood transfusion. Results Among patients, there was no significant correlation between plasma ferritin and adrenal T2*. Significant difference was detected among T2* values of adrenals between the patient and control groups. There was no significant correlation between adrenal gland and liver T2* in β-TM patients, moderate correlation was detected between adrenal T2* and cardiac T2*. Conclusion Adrenal iron in β-TM can be reliably measured in 3 Tesla MRI. The results highlight the absence of correlation between adrenal iron deposition both with serum ferritin and hepatic iron.

  2. Hemoglobinopathies and thalassemia screening among Senoi Orang Asli in Peninsular Malaysia (United States)

    Rong, Danny Koh Xuan; Ismail, Endom; Sabudin, Raja Zahratul Azma Raja; Hussin, Noor Hamidah; Othman, Ainoon


    Orang Asli are the minority indigenous people in Peninsular Malaysia and can be divided into 3 main groups (Negrito, Senoi and Proto Malay) with different six sub-ethnics under each group. Within the Senoi group, the six sub-ethnics are sub-ethnic Mah Meri, Semoq Beri, Che Wong, Jah Hut, Semai and Temiar. This study was aimed to investigate the current prevalence of α- and β-thalassemia and hemoglobinopathies and their mutation types among all six sub-ethnics of Senoi Orang Asli. Blood samples from 685 Senoi participants were collected and sent immediately for routine full blood count analysis and hemoglobin sub-typing. Of 378 subjects screened, 7 subjects were found to be Hemoglobin E (HbE) beta thalassemia carriers, 13 beta thalassaemic, 35 Hemoglobin Constant Spring (HbCS) carriers, 6 compound HbE and HbCS carriers, 32 with HbE disease and 163 HbE heterozygote carriers. The findings of high HbE among Temiars and Jah Huts and high HbCS exclusively in Jah Huts in this study suggest distinct differences across sub-ethnics under Senoi group. Understanding of prevalence and wide spectrum of thalassemia and hemoglobinopathies among Senoi and Orang Asli is essential for national thalassaemia awareness and prevention program, especially in Orang Asli communities.

  3. Study of prevalence of hemoglobinopathy in Sindhi community of Jamnagar, Gujarat: A pilot study

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    Viral M Bhanvadia


    Full Text Available Introduction: Hemoglobinopathies are the most common hereditary disorders in India and pose a major health problem. A pilot study is carried out to find the prevalence of hemoglobinopathies in the Sindhi community of Jamnagar, district of Gujarat, India. Materials and Methods: The present cross-sectional study was undertaken among 109, apparently healthy Sindhi individual from community in Jamnagar, district of Gujarat, India from January to February 2015. All the samples were tested in automated hematology cell counter and cellulose acetate electrophoresis at alkaline pH. Hemoglobin and various red blood cell indices were derived on all samples. HbA2 level of ≥3.8% was taken as confirmatory of Beta-thalassemia trait (BTT. Result: Of 109 samples, BTT and sickle cell trait (SCT were more common in 12-21 years of male and female, respectively. The overall prevalence of hemoglobinopathy was 21/109 (19.26%, comprised of 17 (15.59% cases of BTT and 4 (3.66% cases of SCT. Conclusion: Sindhi community has a high prevalence of hemoglobinopathy mainly BTT. Mass awareness and community screening of individual and proper counseling should be done to reduce the burden of disease

  4. Oxidative modification and poor protective activity of HDL on LDL oxidation in thalassemia. (United States)

    Unchern, Supeenun; Laohareungpanya, Narumon; Sanvarinda, Yupin; Pattanapanyasat, Kovit; Tanratana, Pansakorn; Chantharaksri, Udom; Sibmooh, Nathawut


    Oxidative modification of low-density lipoprotein (LDL) has been reported in thalassemia, which is a consequence of oxidative stress. However, the levels of oxidized high-density lipoprotein (HDL) in thalassemia have not been evaluated and it is unclear whether HDL oxidation may be linked to LDL oxidation. In this study, the levels of total cholesterol, iron, protein, conjugated diene (CD), lipid hydroperoxide (LOOH), and thiobarbituric acid reactive substances (TBARs) were determined in HDL from healthy volunteers and patients with beta-thalassemia intermedia with hemoglobin E (beta-thal/Hb E). The protective activity of thalassemic HDL on LDL oxidation was also investigated. The iron content of HDL(2) and HDL(3) from beta-thal/HbE patients was higher while the cholesterol content was lower than those in healthy volunteers. Thalassemic HDL(2) and HDL(3) had increased levels of lipid peroxidation markers i.e., conjugated diene, LOOH, and TBARs. Thalassemic HDL had lower peroxidase activity than control HDL and was unable to protect LDL from oxidation induced by CuSO(4). Our findings highlight the oxidative modification and poor protective activity of thalassemic HDL on LDL oxidation which may contribute to cardiovascular complications in thalassemia.

  5. Production of beta-globin and adult hemoglobin following G418 treatment of erythroid precursor cells from homozygous beta(0)39 thalassemia patients. (United States)

    Salvatori, Francesca; Breveglieri, Giulia; Zuccato, Cristina; Finotti, Alessia; Bianchi, Nicoletta; Borgatti, Monica; Feriotto, Giordana; Destro, Federica; Canella, Alessandro; Brognara, Eleonora; Lampronti, Ilaria; Breda, Laura; Rivella, Stefano; Gambari, Roberto


    In several types of thalassemia (including beta(0)39-thalassemia), stop codon mutations lead to premature translation termination and to mRNA destabilization through nonsense-mediated decay. Drugs (for instance aminoglycosides) can be designed to suppress premature termination, inducing a ribosomal readthrough. These findings have introduced new hopes for the development of a pharmacologic approach to the cure of this disease. However, the effects of aminoglycosides on globin mRNA carrying beta-thalassemia stop mutations have not yet been investigated. In this study, we have used a lentiviral construct containing the beta(0)39-thalassemia globin gene under control of the beta-globin promoter and a LCR cassette. We demonstrated by fluorescence-activated cell sorting (FACS) analysis the production of beta-globin by K562 cell clones expressing the beta(0)39-thalassemia globin gene and treated with G418. More importantly, after FACS and high-performance liquid chromatography (HPLC) analyses, erythroid precursor cells from beta(0)39-thalassemia patients were demonstrated to be able to produce beta-globin and adult hemoglobin after treatment with G418. This study strongly suggests that ribosomal readthrough should be considered a strategy for developing experimental strategies for the treatment of beta(0)-thalassemia caused by stop codon mutations. Am. J. Hematol., 2009. (c) 2009 Wiley-Liss, Inc.

  6. Hydroxyurea in sickle cell disease--a study of clinico-pharmacological efficacy in the Indian haplotype. (United States)

    Italia, Khushnooma; Jain, Dipty; Gattani, Sushma; Jijina, Farah; Nadkarni, Anita; Sawant, Pratibha; Nair, Sona; Mohanty, Dipika; Ghosh, Kanjaksha; Colah, Roshan


    There is clinical variability in the presentation of sickle cell disease among Indians. Vaso-occlusive crisis is common among non-tribal patients. Hydroxyurea, induces fetal hemoglobin (HbF) synthesis and reduces the clinical severity of sickle cell disease but individual patients have a variable response. This study was undertaken to investigate the efficacy and safety of hydroxyurea in Indians with severe manifestations where the beta(s) gene is linked to the Arab-Indian haplotype and is associated with higher HbF levels. Seventy-seven patients (29 adult sickle homozygous, 25 pediatric sickle homozygous, 23 adult sickle beta-thalassemia) selected for hydroxyurea therapy were evaluated for clinical, hematological, biochemical and genetic parameters and were followed for 24 months. Ninety-eight point seven percent of the sickle chromosomes were linked to the Arab-Indian haplotype, 27% of patients had associated alpha thalassemia and 65% were Xmn I +/+. Seventy-eight percent of the patients had no further crises after starting hydroxyurea. This effect was accompanied by a significant increase in HbF (psickle cell disease.

  7. New mathematical formula for differentiating thalassemia trait and iron deficiency anemia in thalassemia prevalent area: a study in healthy school-age children. (United States)

    Sirachainan, Nongnuch; Iamsirirak, Pornchanok; Charoenkwan, Pimlak; Kadegasem, Praguywan; Wongwerawattanakoon, Pakawan; Sasanakul, Werasak; Chansatitporn, Natkamol; Chuansumrit, Ampaiwan


    Iron deficiency anemia (IDA) and thalassemias are common diseases especially in the Mediterranean, Middle East and Asian regions. Both conditions show the same clinical findings of hypochromic and microcytic red blood cells. Although previous studies have devised mathematical formulae to differentiate between these two conditions, the prevalence of alpha- and beta-thalassemias among the affected populations may undermine the accuracy of these formulae. This study generated a new formula that was able to differentiate IDA and thalassemia traits and to determine the incidence rates of IDA and thalassemia traits. A total of 345 healthy Thai children with a mean age (+/- SD) of 11.3 (+/- 1.7) years were enrolled. Complete blood count, iron status, hemoglobin typing and DNA for alpha-1 thalassemia identification were investigated. Discriminant analysis was used to create a new mathematical formula containing significant variables to differentiate between IDA and thalassemia traits. The new formula of (1.5 Hb-0.05 MCV >14) had a receiver operator characteristic curve of 0.92 in differentiating thalassemia traits from IDA, with sensitivity and specificity of 84.6 and 87.5%, respectively. The incidence of IDA and thalassemia traits in the study group was 12% and 32%, respectively. This formula should be useful as a screening tool to differentiate between these two conditions.

  8. Elevated red blood cell 2,3-diphosphoglycerate levels in black blood donors. (United States)

    Wallas, C H


    Mean levels of 2,3-diphosphoglycerate (DPG) were significantly increased in erythrocytes (RBC) from 43 nonanemic black blood donors (4.80 +/- 0.06 micromoles/l RBC) compared with 22 white donors 4.47 +/- 0.08 micromoles/l RBCs from eight of the 12 black donors with DPG levels greater than 5 micromoles/l RBC. Although a potentially hemolytic disorder could be defined in four (AS hemoglobin, beta-Thalassemia minor, G6PD deficiency), reticulocyte counts were normal. However, when RBCs from the subgroup were compared to RBCs from an additional 25 unselected white donors, the following suggested an abnormally large population of young RBCs in the subgroup: 1) normal or elevated RBC-ATP with normal serum phosphate level; 2) significantly increased activities of RBC age-dependent enzymes hexokinase (p less than 0.02), pyruvate kinase (p less than 0.05), and glutamicoxaloacetic transaminase (p less than 0.01), with normal activity of phosphoglycerate kinase, an age-independent enzyme; 3) decreased dense (older) RBCs as determined by sedimentation in phthalate esters. Since DPG is increased in young RBCs and falls as the RBC ages, loss of older relatively DPG depleted RBCs due to shortened survival could account for the elevated DPG levels seen in the subgroup.

  9. Beta s gene in Central Iran is in linkage disequilibrium with the Indian-Arab haplotype. (United States)

    Rahgozar, S; Poorfathollah, A A; Moafi, A R; Old, J M


    Sickle cell anemia is not considered to be a significant disease in Iran, although the sickle cell trait is estimated to have a high incidence in the Southern provinces. Since 1977, when the presence of a mild sickle cell anemia was reported in this country, there have been no further investigations published giving precise data on the incidence and origins of the sickle cell mutation in Iran. We report here the finding of patients with the sickle cell trait, sickle cell anemia, and sickle-beta thalassemia in Central Iran. A survey of 300 individuals from a village in Southeast Esfahan revealed an incidence of the sickle cell trait of 8.33%. "Cascade screening" enabled 96 relatives in four surrounding villages to be tested, and the at-risk couples were offered counseling as a "sickle cell control program." The hematological indices and HbF levels of the affected patients were determined. The HbF levels were unusually high, ranging from 18% to 41.4%, and SS patients with the highest levels were asymptomatic. Linkage analysis revealed the betaS gene haplotype in this population to be the Indian-Arab haplotype.

  10. Deferasirox effectively decreases iron burden in patients with double heterozygous HbS/β-thalassemia. (United States)

    Voskaridou, Ersi; Plata, Eleni; Douskou, Marousa; Sioni, Anastasia; Mpoutou, Efrosini; Christoulas, Dimitrios; Dimopoulou, Maria; Terpos, Evangelos


    Iron overload is present in several cases of double heterozygous sickle-cell/beta-thalassemia (HbS/β-thal). Deferasirox is an orally administered iron chelator which is effective on iron overloaded patients with transfusion-dependent anemia. The aim of this study was to investigate the efficacy and safety of deferasirox on HbS/β-thal patients with iron overload. We evaluated 31 adult patients with HbS/β-thal (14M/17F; median age 41 years) who had serum ferritin levels >1,000 ng/mL and who were sporadically transfused. Total iron burden was monitored by measuring serum ferritin levels before and monthly after starting deferasirox, while liver iron concentration and cardiac iron burden were measured by magnetic resonance imaging (MRI) T2 and T2* parameters at baseline and 12 months after deferasirox treatment. Deferasirox managed to reduce the mean serum ferritin levels after 12 months of treatment from 1,989 ± 923 to 1,008 ± 776 ng/mL (P deferasirox provided effective control of iron levels (mainly of the liver) in minimally transfused patients with HbS/β-thal, without significant adverse events, at similar doses to those studied widely for the treatment of patients with thalassemia syndromes.


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    Giorgio La Nasa


    Full Text Available Abstract Although the past few decades have shown an improvement in the survival and complication-free survival rates in patients with beta-thalassemia major and gene therapy is already at an advanced stage of experimentation, hematopoietic stem cell transplantation (HSCT continues to be the only effective and realistic approach to the cure of this chronic non-malignant disease. Historically, human leukocyte antigen (HLA-matched siblings have been the preferred source of donor cells owing to superior outcomes compared with HSCT from other sources. Nowadays, the availability of an international network of voluntary stem cell donor registries and cordon blood banks has significantly increased the odds of finding a suitable HLA matched donor. Stringent immunogenetic criteria for donor selection have made it possible to achieve overall survival (OS and thalassemia-free survival (TFS rates comparable to those of sibling transplants. However, acute and chronic graft-versus-host disease (GVHD remains the most important complication in unrelated HSCT in thalassemia, leading to considerable rates of morbidity and mortality for a chronic non-malignant disease. A careful immunogenetic assessment of donors and recipients makes it possible to individuate appropriate strategies for its prevention and management. This review provides an overview on recent insights about immunogenetic factors involved in GVHD, which seem to have a potential role in the outcome of transplantation for thalassemia.

  12. Genetic counseling for thalassemia in the Islamic Republic of Iran. (United States)

    Strauss, Bernard S


    The response of groups to pressing medical problems cannot be predicted on theoretical grounds. An example is the program for the control of beta-thalassemia in Iran, a country with a tradition of inbreeding and a conservative religious culture, and in which thalassemia is common. Thalassemia is largely treatable, but the treatment is lifelong and onerous and creates a serious economic burden for the individual family and for the national health budget. The genetics are simple, and inexpensive screening tests are available to identify carriers. An Iranian program requiring mandatory premarital screening was started in 1997, and between 1998 and 2005 the laws of the country were modified to permit abortion of affected fetuses. The story of this effort indicates how a country with a social system very different from that of the United States responded to a medical problem with significant ethical overtones. The Iranian experience supports the optimistic view that societies can react to pressing problems with pragmatic rather than theoretical solutions.

  13. Raman Tweezers as a Diagnostic Tool of Hemoglobin-Related Blood Disorders

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    Giulia Rusciano


    Full Text Available This review presents the development of a Raman Tweezers system for detecting hemoglobin-related blood disorders at a single cell level. The study demonstrates that the molecular fingerprint insight provided by Raman analysis holds great promise for distinguishing between healthy and diseased cells in the field of biomedicine. Herein a Raman Tweezers system has been applied to investigate the effects of thalassemia, a blood disease quite diffuse in the Mediterranean Sea region. By resonant excitation of hemoglobin Raman bands, we examined the oxygenation capability of normal, alpha- and beta-thalassemic erythrocytes. A reduction of this fundamental red blood cell function, particularly severe for beta-thalassemia, has been found. Raman spectroscopy was also used to draw hemoglobin distribution inside single erythrocytes; the results confirmed the characteristic anomaly (target shape, occurring in thalassemia and some other blood disorders. The success of resonance Raman spectroscopy for thalassemia detection reported in this review provide an interesting starting point to explore the application of a Raman Tweezers system in the analysis of several blood disorders.

  14. [Anemia in workers exposed to lead: update on differential diagnosis]. (United States)

    Di Lorenzo, L; Soleo, L; Cassano, F; Elia, G; Schiavulli, N; Martino, M G; Corfiati, M; Bulfaro, D; Apostoli, P


    Occupational lead exposure can cause anemia at blood lead levels >50 microg/dl, as high as rarely occurs in industrialized countries nowadays. Whereas other forms of anemia are fairly probable to be found in lead exposed workers, especially in areas highly endemicfor extraoccupational anemias, such as beta thalassemia and iron deficiency anemia. The etiology of anemias has to be correctly defined in order to assess suitable therapeutical approaches and medicolegal consequences. The objective of this study is to verify in male lead exposed workers whether an accurate evaluation of hemocromocytometric parameters and of usual biological indices of lead exposure and effect on heme can differentiate the most common forms of anemia in Southern Italy. 68 workers occupationally exposed to low to moderate lead doses were studied and 59 workers of an alimentary plant have been taken as control group. On venous blood samples collected from these workers a complete hemocromocytometric test was performed and blood lead and erythrocytic zincoprotoporphyrin were determined. Anemia (Hb lead exposed workers and in a nonexposed worker. The reasoned evaluation of laboratory parameters led to identify among lead exposed workers four subjects with high probability of beta-thalassemic trait and two with lead poisoning anemia. Moreover a diagnostic algorithm was developed based on literature that seems to be able to discriminate lead poisoning from other causes of anemia in lead exposed workers in this study.

  15. Uso de índices hematimétricos no diagnóstico diferencial de anemias microcíticas: uma abordagem a ser adotada? Are Red Blood Cells (RBC indices valuable on differentiating microcytic anemias?: Differential diagnosis of microcytic anemia is a complex task, with considerable cost

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    years-old, and ferritin measurement and hemoglobin electrophoresis were performed. We classified our patients in three groups: Iron-deficiency anemia (AF; 26 patients, beta-thalassemia minor (BTM; n=17 and non-iron-deficiency-non-beta-thalassemia (ANFNT; n=9. We evaluated the following RBC indices for group discrimination, with variance and ROC curve analysis: RBC, MCV, MCH, RDW, England's index and Green's index. RESULTS: None of the indices allowed complete discrimination of all groups. We have established limits for each of the indices, and sensitivity (S, specificity(E, positive and negative predictive values and test efficiency were determined. BTM was better distinguished from the other groups by RBC (above 5 millions/mL and England's index (<6, both with S=82.3% and E of 82.8%. A RDW above 16% was the best index of AF, with S=69.2% and E= 80.7%. CONCLUSIONS: Presumptive diagnosis of AF is troublesome when using RBC indices; diagnosis should be based on complete laboratory evaluation. Elevated RBC levels, specially above 5 millions/muL, in anemic patients with microcytosis are important indicatives of BTM, and confirmatory tests are suggested.

  16. Uso da fluorescência de raios X portátil (XRF in vivo como técnica alternativa para acompanhamento dos níveis de ferro em pacientes com sobrecarga de ferro The in vivo use of portable X-ray fluorescence as an alternative technique for the accompaniment of iron levels in patients with iron loading

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    Marcelo Estevam


    Full Text Available Foi investigada a viabilidade da aplicação da técnica de fluorescência de raios X (XRF como alternativa para acompanhamento dos níveis de ferro em pacientes portadores de talassemia maior (beta-thalassemia e hemocromatose hereditária (HH. As medidas foram realizadas no Hemocentro do Hospital Universitário e no Laboratório de Física Nuclear Aplicada da Universidade Estadual de Londrina. Foi acompanhada uma portadora de talassemia maior e quatro pessoas sadias. Foi utilizado um sistema portátil de XRF constituído de uma fonte de Raios X de 238Pu e um detector de SiPIN diodo, para as medidas in vivo na mão. O sistema foi calibrado medindo simulados de solução aquosa com 15 a 150 ppm de ferro. A duração de cada medida foi de 50 s. O limite de detecção (LLD atingido foi de 13 ppm de ferro. A dose de radiação na pele foi de 10 mSv. A paciente de talassemia apresentou 74 ± 6 ppm de ferro, enquanto pessoas sadias apresentaram valor médio de 53 ± 5 ppm de ferro. Os resultados estão de acordo com a literatura, que informa níveis de ferro na pele de 15 a 60 ppm em pessoas sadias e de 70 a 150 ppm em pacientes portadores da talassemia maior. Foi concluído ser viável a aplicação da XRF para acompanhamento de pacientes de talassemia maior e HH.The viability of the X-ray fluorescence technique as an alternative to follow up iron levels in patients suffering from thalassemia major (beta-thalassemia and hereditary hemochromatosis was investigated. The measurements were carried out in the University Hospital Blood Center and in the Laboratory of Applied Nuclear Physics of the State University of Londrina. One thalassemia major patient and four healthy individuals were enrolled in the study. A portable X-ray fluorescence system consisting in a 238Pu X-ray source and a Si PIN diode detector was used for in vivo measurements of the hand. The system was calibrated using 15 to 150 ppm concentrations of iron in an aqueous solution. The

  17. Application of Full Automated Capillary Electrophoresis System in the Analysis of Thalassemia%全自动毛细管电泳仪在成人珠蛋白生成障碍性贫血筛查中的应用评价

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    万志丹; 黄湘; 吴学威; 李冬秀; 郑国兵; 姚英姿; 梁睿


    目的 探讨全自动毛细管电泳仪在成人珠蛋白生成障碍性贫血筛查中的应用价值.方法 使用法国Sebia公司的Capillarys2全自动毛细管电泳仪对18 003例成人血标本进行血红蛋白电泳分析,检测HbA,HbF,HbA2和异常血红蛋白含量,对筛查表型阳性的病例召回进行基因分析.结果 18 003例成人标本筛查出α珠蛋白生成障碍性贫血表型阳性者2 226例,筛查阳性率12.36%,其中召回1 070例行基因分析,626例为α珠蛋白基因缺失,符合率58.50%;β珠蛋白生成障碍性贫血表型阳性者1 329例,筛查阳性率7.38%,其中召回733例行基因分析,710例为β珠蛋白基因突变,符合率96.86%.结论 全自动毛细管电泳作为一种新型液相分离技术,具有快速、灵敏度高、分辨率高等优点,能对HbA2进行准确的定位及定量,可初步区分α,β珠蛋白生成障碍性贫血,有效筛出高危患者,全自动毛细管电泳分析技术与基因分析有良好的符合性,为珠蛋白生成障碍性贫血的诊断提供重要依据.%Objective To assess capillary electrophoresis system in the analysis of Thalassemia. Methods Using France Sebia company Capillary 2 automatic capillary electrophoresis instrument analysis 18 003 cases of adult hemoglobin electrophoresis, detection of HbA,HbF,HbA2 and abnormal hemoglobin content,the positive phenotypes cases were recalled for genetic analysis. Results 18 003 cases of adult specimens for alpha thalassemia phenotype was positive in 2 226 cases, screening positive rate 12. 36%. Recalled of 1 070 for gene detection,626 patients for alpha globin gene deletion,with coincidence rate 58. 50%. Beta thalassemia phenotype was positive in 1 329 cases,screening positive rate 7. 38%. Recalled of 733 for gene detection, 710 patients for beta globin gene mutation, with coincidence rate 96. 86%. Conclusion Automatic capillary electrophoresis as a new type of liquid phase separation technology,has the advantages

  18. Prevalência de talassemias e hemoglobinas variantes em pacientes com anemia não ferropênica Prevalence of thalassemias and variant hemoglobins in patients with non-ferropenic anemia

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    Sandrine C. Wagner


    patients with non-ferropenic anemia carried some type of inherited anemia: 25.9% of heterozygous alpha-thalassemia, 32.8% of heterozygous beta-thalassemia, 3.4% of heterozygosity for hemoglobin S (Hb AS and 1.7% of homozygosity for hemoglobin C (Hb CC. Inherited anemias were detected in 14.1% of the control group: 11.5% of alpha-thalassemia, 0.9% of beta-thalassemia, 1.3% of heterozygosity for hemoglobin S (Hb AS and 0.4% of heterozygosity for hemoglobin C (Hb AC. The results obtained showed that the prevalence of variant thalassemias and hemoglobins in the control group is coincident with that described in the literature. However, physicians and health services should be informed about the overwhelming prevalence of these inherited homeopathies in individuals with non-ferropenic anemia, due to its importance in the definitive diagnosis of anemia and for the correct therapeutic proceedings.

  19. 地中海贫血胸部髓外造血影像表现(附6例分析)%Imaging findings of intrathoracic extramedullary hematopoiesis in thalassemia:sixe cases report

    Institute of Scientific and Technical Information of China (English)

    杨军克; 黄筠洋; 俞雷; 岑炳奎; 黄晓


    目的 探讨地中海贫血胸部髓外造血组织增生的影像表现,提高影像诊断和鉴别诊断.方法 回顾性分析经临床证实的6例地中海贫血继发髓外造血(EMH)的胸部影像学资料,β-地中海贫血5例,α-地中海贫血1例.胸部X线平片6例,CT平扫4例,MRI平扫及增强2例.结果 影像表现为两侧脊柱旁瘤样软组织肿块影,4例合并胸壁肋骨下EMH,1例合并胸壁肋骨下、肺部及胸段椎管内多部位EMH;2例β-地中海贫血EMH见纤细骨针样钙化,MRI上呈等T1等T2信号,轻-中度强化;1例α-地中海贫血EMH巨大,密度不均,T1、T2呈等、高信号,轻-中度不均匀强化,2年后X线平片观察EMH大小有变化.CT引导下穿刺活检,镜下大部分为脂肪组织,并见片状坏死灶.结论 地中海贫血继发EMH,依据影像表现特点,结合临床及实验室检查可做出正确诊断.%Objective To investigate the imaging findings of intrathoracic extramedullary hematopoiesis(EMH) in thalassemia,so that to improve its diagnosis and differential diagnosis.Methods Clinical and imaging findings of 6 cases with EMH in thalassemia were retrospectively analyzed.There were Beta-thalassemia in 5 cases and Alpha-thalassemia in 1 case; 6 cases were examined by chest X-ray,CT plain scans in A cases, MRI plain scan and contrast-enhanced scan in 2 cases were performed.Results The imaging features of EMH were tumor-like masses at the posterior mediastinum of bilateral paravertebral, and accompanied with chest wall EMH in 4 cases,chest wall,lung and spinal canal EMH in 1 case.The calcific shadows of bony trabecula-like inside the masses were seen in 2 cases with Beta-thalassemia, and on MRI, EMH were of same signal intensity as compared to adjacent muscles on T1WI and T2WI,and slight to mild homogeneous enhancement after intravenous contrast administration.1 case with Alpha-thalassemia, the signal intensity or density of the lesions was inhomogeneous,and isointense and high signal

  20. 部分脾栓塞治疗小儿脾机能亢进%Partial Splenic Embolization in the Treatment of Hypersplenism in Children

    Institute of Scientific and Technical Information of China (English)

    周晓初; 张寿熙; 阮庆兰; 郭筱兰; 叶明; 许林峰; 杨建勇; 冯敢生; 王碧玉


    Six patients with beta-thalassemia major and four patients with hereditary spherocytosis underwent partial splenic embolization (PSE)as alternative to splenectomy for hypersplenism,age ranged 1-5 yrs.About 50% -60%of the spleen being embolized with Gelfoam(0.5mm×0.5mm×1.0mm).all patients were followed up from 6 to 12 mos.These results disclosed elevation of white blood cell count(P<0.01),the platelet count(P<0.01),significant shrinking of spleen(P<0.01=.but normal lymphocyte subsets and immunoglobulin.Ten patients had low fever and mild oain in left hypochondrium,there was no splcnic abscess nor other noticible complications during the treatment.%总结了应用部分脾栓塞术治疗10例小儿血液病脾肿大、脾机能亢进的近期临床疗效,全部病例随访6个月以上.术后血小板及白细胞计数均较术前有显著升高,术后输血量明显减少,脾脏较术前显著缩小,脾机能亢进得到很好地控制,而机体免疫球蛋白各值,T淋巴细胞亚群及天然杀伤细胞百分值均较治疗前无显著变化.

  1. Hemoglobinopathies in newborns in the southern region of the Triângulo Mineiro, Brazil. Cross-sectional study

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    Aline Menezes Carlos

    Full Text Available ABSTRACT CONTEXT AND OBJECTIVE: Hemoglobinopathies are among the commonest and most widespread genetic disorders worldwide. Their prevalence varies according to ethnic composition and/or geographical region. The aim of this study was to investigate the presence of hemoglobinopathies and their association with ethnicity among 1,004 newborns, to confirm the guideline of the Brazilian National Neonatal Screening Program. DESIGN AND SETTING: Cross-sectional study conducted in a public referral hospital in the Triângulo Mineiro region, Minas Gerais, Brazil. METHODS: Qualitative assessment of hemoglobin was performed through electrophoresis on cellulose acetate: at alkaline pH to identify the hemoglobin (Hb profile and at acid pH to differentiate Hb S from Hb D and Hb C from Hb E and others that migrate to similar positions at alkaline pH. Neutral pH was used to detect Hb Bart's identified in alpha thalassemia (α-thal. The elution method after electrophoresis was used to quantitatively assess hemoglobins. RESULTS: There was predominance of α-thal, with 105 cases (10.46%, followed by Hb S with 61 cases (6.08%, comprising 46 Hb AS, 2 Hb SS and 13 Hb S/α-thal, 9 cases (0.9% of Hb AC and 6 cases (0.6% suggestive of beta thalassemia (β-thal. The frequency of hemoglobinopathies was significantly higher among Afro-descendants. CONCLUSIONS: These findings corroborated of the National Neonatal Screening Program for diagnosing sickle cell disease and Hb C, Hb D, Hb E and β-thal hemoglobinopathies.

  2. Analysis of hemoglobin electrophoresis results and physicians investigative practices in Saudi Arabia

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    Syed Riaz Mehdi


    Full Text Available Background and Objectives: Riyadh and central province falls in a moderate prevalent zone of hemoglobinopathies in Saudi Arabia. However, it has been observed that the physicians working in Saudi Arabia invariably advise all cases of anemia for hemoglobin electrophoresis (HE. The present work was carried out to study the yield of the HE in Riyadh and the investigative practices of the physicians advising HE. Settings and Design: The study was carried out in the hospitals of King Saud University from 2009 to 2011 in order to assess the yield of HE in referred cases of clinical anemia. Materials and Methods: A total of 1073 cases divided in two groups of males and females had undergone complete blood count and red blood cell morphology. Cellulose acetate HE was performed and all the positive results were reconfirmed on the high performance liquid chromatography (HPLC. The results were analyzed for the type of hemoglobinopathies. For statistical analysis Statistical Package for Social Sciences 15 version (SPSS Inc., Chicago, IL, USA was used. Results: A total of 405 males and 668 females blood samples were included in the present study. 116 (28.5% males and 167 (25% females showed an abnormal pattern on HE. The incidence of beta thalassemia trait was higher in females while sickle cell trait was predominantly seen in males. Red cell indices were reduced considerably in thalassemias, but were unaffected in sickle cell disorders, except those which had concurrent alpha trait. The total yield of HE was 26.6% which was much less than expected. Conclusion: The physicians are advised to rule out iron deficiency and other common causes of anemia before investigating the cases for hemoglobinopathies, which employs time consuming and expensive tests of HE and HPLC.

  3. Magnetic resonance imaging signal reduction may precede volume loss in the pituitary gland of transfusion-dependent beta-thalassemic patients

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    Hekmatnia, Ali; Rahmani, Ali Asghar; Adibi, Atoosa (Image Processing and Signal Research Center, Dept. of Radiology, Isfahan Univ. of Medical Sciences, Isfahan (Iran)); Radmard, Amir Reza (Dept. of Radiology, Shariati Hospital, Tehran Univ. of Medical Sciences, Tehran (Iran)); Khademi, Hooman (Shariati Hospital, Tehran Univ. of Medical Sciences, Tehran (Iran)), e-mail:


    Background: Pituitary iron overload in patients with transfusion-dependent beta-thalassemia may lead to delayed puberty. Magnetic resonance imaging (MRI) has the potential to estimate tissue iron concentration by detecting its paramagnetic effect and hypophyseal damage by measuring its dimensions indirectly. Purpose: To investigate the association of pituitary MRI findings and pubertal status in thalassemic patients as well as to demonstrate any priority in appearance of them. Material and Methods: Twenty-seven beta-thalassemic patients, aged 15-25 years, were divided into 13 with (group A) and 14 without hypogonadism (group B), matched by age, gender, duration of transfusion, and chelation therapy. Thirty-eight age- and sex-adjusted healthy control individuals were also included (group C). All participants underwent pituitary MRI using a 1.5T unit. Pituitary-to-fat signal intensity ratios (SIR) were calculated from coronal T2-weighted images. Estimated pituitary volumes were measured using pituitary height, width, and length on T1-weighted images. Results: The mean values of pituitary-to-fat SIRs were significantly lower in group A as compared with group B (P <0.001), and likewise group B had statistically lower values than group C (P=0.03). The pituitary height and volume were significantly decreased in group A compared to group B (P = 0.006 and P = 0.002, respectively), while these differences did not demonstrate statistically significance between groups B and C. Conclusion: Pituitary MRI findings such as signal intensity reduction and decrease in volume can be useful markers in estimating pituitary dysfunction in beta-thalassemic patients. Compared to healthy controls, lower values of pituitary-to-fat SIRs in thalassemic patients experiencing normal puberty, without marked decrease in volume, indicate that signal reduction may precede volume loss and could be expected first on MRI

  4. β-Thalassemia Intermedia: A Bird’s-Eye View

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    Anthony Haddad


    Full Text Available Beta-thalassemia is due to a defect in the synthesis of the beta-globin chains, leading to alpha/beta imbalance, ineffective erythropoiesis, and chronic anemia. The spectrum of thalassemias is wide, with one end comprising thalassemia minor, which consists of a mild hypochromic microcytic anemia with no obvious clinical manifestations, while on the other end is thalassemia major, characterized by patients who present in their first years of life with profound anemia and regular transfusion requirements for survival. Along the spectrum lies thalassemia intermedia, a term developed to describe patients with manifestations that are neither mild enough nor severe enough to be classified in the spectrum’s extremes. Over the past decade, our understanding of β-thalassemia intermedia has increased tremendously with regards to molecular information as well as pathophysiology. It is now clear that β-thalassemia intermedia has a clinical presentation as well as complications associated with the disease that are different from those of β-thalassemia major. This review is designed to tackle issues related to β-thalassemia intermedia from the basic definition of the disease to paramedical issues, namely the quality of life in these patients. Genetics and pathophysiology are revisited, as well as the complications specific to this disease. These complications include effects on several organ systems, including the cardiovascular, hepatic, endocrine, renal, brain, and skeletal systems. Extramedullary hematopoiesis is also discussed in this article. Risk factors are highlighted and cutoffs are identified to minimize morbidities in β-thalassemia intermedia. Several treatment modalities are considered by shining a light on the pros and cons of each modality, as well as the role of special pharmacological agents in the progress of the disease and its morbidities. Finally, health-related quality of life is discussed in these patients with a direct comparison

  5. On improvement in ejection fraction with iron chelation in thalassemia major and the risk of future heart failure

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    Carpenter JP


    Full Text Available Abstract Background Trials of iron chelator regimens have increased the treatment options for cardiac siderosis in beta-thalassemia major (TM patients. Treatment effects with improved left ventricular (LV ejection fraction (EF have been observed in patients without overt heart failure, but it is unclear whether these changes are clinically meaningful. Methods This retrospective study of a UK database of TM patients modelled the change in EF between serial scans measured by cardiovascular magnetic resonance (CMR to the relative risk (RR of future development of heart failure over 1 year. Patients were divided into 2 strata by baseline LVEF of 56-62% (below normal for TM and 63-70% (lower half of the normal range for TM. Results A total of 315 patients with 754 CMR scans were analyzed. A 1% absolute increase in EF from baseline was associated with a statistically significant reduction in the risk of future development of heart failure for both the lower EF stratum (EF 56-62%, RR 0.818, p Conclusion These data show that during treatment with iron chelators for cardiac siderosis, small increases in LVEF in TM patients are associated with a significantly reduced risk of the development of heart failure. Thus the iron chelator induced improvements in LVEF of 2.6% to 3.1% that have been observed in randomized controlled trials, are associated with risk reductions of 25.5% to 46.4% for the development of heart failure over 12 months, which is clinically meaningful. In cardiac iron overload, heart mitochondrial dysfunction and its relief by iron chelation may underlie the changes in LV function.

  6. Bone marrow MR imaging as predictors of outcome in hemopoietic stem cell transplantation

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    Shen, Jun; Cheng, Li-Na; Duan, Xiao-Hui; Liang, Bi-Ling [Sun Yat-sen University, Department of Radiology, Guangzhou, Guangdong (China); Second Affiliated Hospital, Guangzhou, Guangdong (China); Griffith, James F. [Chinese University of Hong Kong, Prince of Wales Hospital, Department of Diagnostic Radiology and Organ Imaging, Shatin, Hong Kong SAR (China); Xu, Hong-Gui [Sun Yat-sen University, Department of Pediatrics, Guangzhou, Guangdong (China); Second Affiliated Hospital, Guangzhou, Guangdong (China)


    The purpose of this study is to investigate the role of femoral marrow MR imaging as predictor of outcome for hemopoietic stem cell transplantation (HSCT) in beta-thalassemia major. MR imaging of the proximal femur, including T1- and T2-weighted spin echo and short-tau inversion recovery and in-phase and out-of-phase fast field echo images, was prospectively performed in 27 thalassemia major patients being prepared for HSCT. The area of red marrow and its percentage of the proximal femur were measured, and the presence of marrow hemosiderosis was assessed. Age-adjusted multivariate logistic regression was used to determine the relationship between red marrow area percentage and marrow hemosiderosis and HSCT outcome. Red area percentage were less in patients with successful (90.25{+-}4.14%) compared to unsuccessful transplants (94.54% {+-}2.93%; p=0.01). Red marrow area percentage correlated positively with duration of symptoms(r=0.428, p=0.026) and serum ferritin (r=0.511, p=0.006). In multivariate-adjusted logistic regression analyses, red marrow area percentage was significantly inversely associated with successful HSCT (OR=1.383, 95% CI: 1.059-1.805, p=0.005). Marrow hemosidersosis and duration of sympotms and serum ferritin were not associated with HSCT outcome(p=0.174, 0.974, 0.762, respectively). Red marrow area percentage of proximal femur on MR imaging is a useful predictor of HSCT outcome. (orig.)

  7. Disease-associated mutations that alter the RNA structural ensemble.

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    Matthew Halvorsen


    Full Text Available Genome-wide association studies (GWAS often identify disease-associated mutations in intergenic and non-coding regions of the genome. Given the high percentage of the human genome that is transcribed, we postulate that for some observed associations the disease phenotype is caused by a structural rearrangement in a regulatory region of the RNA transcript. To identify such mutations, we have performed a genome-wide analysis of all known disease-associated Single Nucleotide Polymorphisms (SNPs from the Human Gene Mutation Database (HGMD that map to the untranslated regions (UTRs of a gene. Rather than using minimum free energy approaches (e.g. mFold, we use a partition function calculation that takes into consideration the ensemble of possible RNA conformations for a given sequence. We identified in the human genome disease-associated SNPs that significantly alter the global conformation of the UTR to which they map. For six disease-states (Hyperferritinemia Cataract Syndrome, beta-Thalassemia, Cartilage-Hair Hypoplasia, Retinoblastoma, Chronic Obstructive Pulmonary Disease (COPD, and Hypertension, we identified multiple SNPs in UTRs that alter the mRNA structural ensemble of the associated genes. Using a Boltzmann sampling procedure for sub-optimal RNA structures, we are able to characterize and visualize the nature of the conformational changes induced by the disease-associated mutations in the structural ensemble. We observe in several cases (specifically the 5' UTRs of FTL and RB1 SNP-induced conformational changes analogous to those observed in bacterial regulatory Riboswitches when specific ligands bind. We propose that the UTR and SNP combinations we identify constitute a "RiboSNitch," that is a regulatory RNA in which a specific SNP has a structural consequence that results in a disease phenotype. Our SNPfold algorithm can help identify RiboSNitches by leveraging GWAS data and an analysis of the mRNA structural ensemble.

  8. Diagnosis of a rare double heterozygous Hb D Punjab/Hb Q India hemoglobinopathy using Sebia capillary zone electrophoresis

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    Sushama Parab


    Full Text Available In India, hemoglobinopathies constitute a major genetic disorder and hemoglobin variants such as Hb S, Hb D Punjab, and Hb E are the most common ones. Other variants include Hb Q India, Hb Lepore, Hb J Meerut, Hb D Iran, etc. These variants show heterozygous state along with beta thalassemia. However, compound heterozygosities among these variants are very rare. Ethylenediaminetetraacetic acid whole blood sample received for routine thalassemia screening was subjected to alkaline electrophoresis using automated capillary zone electrophoresis. Suspecting the presence of rare variants, further analysis was carried out using Bio-Rad D10 and Tosoh G8 high-performance liquid chromatography (HPLC systems. Capillary zone electrophoretograms showed the presence of peaks in zone Hb A, Hb D, a fused peak in Hb A2, and a small peak in Z1 zone. Bio-Rad and Tosoh chromatograms also indicated the presence of four peaks which are identified as Hb A, Hb D Punjab, Hb Q India, and hybrid of Hb D Punjab/Hb Q India. A peak in Hb D zone of capillary was due to co-migration of Hb D Punjab and Hb Q India variants. Small peak in Z1 zone indicated the presence of alpha chain variant Hb Q India. The findings were further confirmed by HPLC results and molecular genetic studies. The present study reports for the 1 st time a rare hemoglobinopathy of double heterozygosity for Hb D Punjab, Hb Q India on Capillarys 2 Flex Piercing analyzer and is forth reported case for this rare hemoglobinopathy.

  9. Regression of extramedullary hematopoiesis with hydroxyurea therapy in ß-thalassemia intermedia Regressão da hematopoese extramedular na talassemia intermédia após terapia com hidroxiuréia

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    Perla Vicari


    Full Text Available Excessive ineffective erythropoiesis in thalassemia intermedia may cause extramedullary hematopoiesis (EMH, resulting in spleen and liver enlargement or masses in several tissues, mainly paravertebrally. Other less frequent locations of diffuse compensatory EMH are kidneys, adrenal glands, breasts, spinal cord, pleura, pericardium, duramater, adipose tissue and skin, although intrathoracic extramedullary hematopoiesis is a rare condition. Management strategies have included radiation and transfusion therapy. Hydroxyurea with transfusion therapy has been associated with clinical regression of EMH in thalassemia. We report an uncommon case of intrathoracic EMH in a patient with beta-thalassemia intermedia, that showed significant recovery with HU therapy.A excessiva eritropoese ineficaz na talassemia pode causar hemato-poese extramedular (HEM, resultando em hepatomegalia, esplenomegalia e massas de tecido hematopoético em diversos tecidos. Localizações de HEM compensatória menos freqüentes são rins, glândulas adrenais, canal medular, pleura, pericárdio, duramáter, tecido adiposo e pele. Entretanto, HEM intratorácica é condição rara. Estratégias terapêuticas incluem radiação e transfusões sanguíneas. O uso de hidroxiuréia concomitante a terapêutica transfusional foi associado à regressão clínica da HEM na talassemia. Nós descrevemos um caso de HEM intratorácica em paciente portadora de talassemia intermédia, com significante regressão do quadro após terapêutica isolada com hidroxiuréia.

  10. Hb Bronte or alpha93(FG5)Val-->Gly: a new unstable variant of the alpha2-globin gene, associated with a mild alpha(+)-thalassemia phenotype. (United States)

    Lacerra, Giuseppina; Testa, Rosario; De Angioletti, Maria; Schilirò, Gino; Carestia, Clementina


    We report a new unstable variant identified in three carriers of a family from East Sicily; it was named Hb Bronte after the place from which the family originated. DNA sequencing from nucleotides -181 to +894 (alpha1) and to +884 (alpha2) revealed a GTG-->GGG substitution at codon 93 of the alpha2-globin gene. The MCV and MCH values were at the lower end of the normal range in the carriers. On cation exchange high performance liquid chromatography (HPLC), the Hb A2 level was apparently increased to around 6%, and a small abnormal peak (0.3-0.4%) was detected after Hb A2. Two abnormal bands were detected by cellulose acetate electrophoresis: a major band (about 3-4%) migrated between Hb A and Hb F; a minor band (<1%) migrated between Hb A2 and carbonic anhydrase. Normal values of Hb A2 were detected by DEAE microchromatography. On reversed phase HPLC the variant chain was not detected, and most likely it was eluted with the alpha chain peak. The isopropanol stability test was very slightly positive in the carriers. Hemolytic symptoms were absent with the exception of indirect bilirubin, which was at high borderline in 2/3 carriers. In biosynthesis in vitro, the specific activity of the alpha chains was much higher than that of the beta-globin chains, and the alpha/beta biosynthetic ratio in the mother and proband was of the beta-thalassemia (thal) type (2.24 and 2.54, respectively). Time course experiments showed that the increase of the 3H-specific activity of the peak containing normal and variant alpha chains was not linear and was much higher than that of beta chains; moreover, the alpha/beta biosynthetic ratio varied during the 2 hours incubation.

  11. Liver, bone marrow, pancreas and pituitary gland iron overload in young and adult thalassemic patients: a T2 relaxometry study

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    Argyropoulou, Maria I.; Astrakas, Loukas; Metafratzi, Zafiria; Efremidis, Stavros C. [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); Kiortsis, Dimitrios N. [University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece); Chalissos, Nikolaos [University of Ioannina, Department of Radiology, Medical School, Ioannina (Greece); University of Ioannina, Laboratory of Physiology, Medical School, Ioannina (Greece)


    Thirty-seven patients with {beta}-thalassemia major, including 14 adolescents (15.2 {+-} 3.0 years) and 23 adults (26.4 {+-} 6.9 years), were studied. T2 relaxation time (T2) of the liver, bone marrow, pancreas and pituitary gland was measured in a 1.5-Tesla magnetic resonance (MR) imager, using a multiecho spin-echo sequence (TR/TE 2,000/20, 40, 60, 80, 100, 120, 140, 160 ms). Pituitary gland height was evaluated in a midline sagittal scan of a spin-echo sequence (TR/TE, 500/20 ms). The T2 of the pituitary gland was higher in adolescents (59.4 {+-} 15 ms) than in adults (45.3 {+-} 10.4 ms), P < 0.05. The T2 of the pancreas was lower in adolescents (43.6 {+-} 10.3 ms) than in adults (54.4 {+-} 10.4 ms). No difference among groups was found in the T2 of the liver and bone marrow. There was no significant correlation of the T2 among the liver, pancreas, pituitary gland and bone marrow. There was no significant correlation between serum ferritin and T2 of the liver, pancreas and bone marrow. Pituitary T2 showed a significant correlation with pituitary gland height (adolescents: R = 0.63, adults: R = 0.62, P < 0.05) and serum ferritin (adolescents: R = -0.60, adults: R = -0.50, P < 0.05). In conclusion, iron overload evaluated by T2 is organ specific. After adolescence, age-related T2 changes are predominantly associated with pituitary siderosis and fatty degeneration of the pancreas. Pituitary size decreases with progressing siderosis. (orig.)

  12. Psychosocial problems in thalassemic adolescents and young adults

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    Manoj Jain


    Full Text Available Background: With the availability of better treatment regimen, life span of thalassemic patients is increasing. Chronic nature of thalassemia and its intensive and demanding treatment result in significant psychologic burden on the patients and their families. A lot has been studied about beta-thalassemia major but little attention has been paid to the psychological aspect of this disease. Hence, the study was planned to analyse the psychosocial problems in thalassemic adolescents and young adults. Materials and Methods: This was a cross-sectional study, conducted from January 2007 to March 2008 in thalassemic day-care centre of a tertiary care teaching hospital. Fifty four thalassemic children and controls above 9 years of age were enrolled. Psychosocial assessment done with assessment of Finer Psychopathology using ICMR Symptom checklist (ICMR task force, 1983. The prevalence of various problems was calculated and compared with controls. Student′s t-test and Chi-square test were used for testing differences in variables. Results: Patients were divided into three groups - Group A (10-15 years, 30 patients; Group B (15-20 years, 18 patients, and Group C (20-25 years, 6 patients. In group A, behavior problems were common (12 patients -40% (P< 0.001, significant. In group B, mood disorders were common (8 patients, 44% (P< 0.001, significant. In group C, psychotic symptoms were common (3 patients, 50% (P< 0.05, significant. Conclusion: Our findings support the hypothesis that psychosocial problems are more in thalassemic adolescents and young adults. Psychosocial aspects need to be addressed in the overall treatment of children with thalassemia.

  13. Exercise tolerance, lung function abnormalities, anemia, and cardiothoracic ratio in sickle cell patients. (United States)

    van Beers, Eduard J; van der Plas, Mart N; Nur, Erfan; Bogaard, Harm-Jan; van Steenwijk, Reindert P; Biemond, Bart J; Bresser, Paul


    Many patients with sickle cell disease (SCD) have a reduced exercise capacity and abnormal lung function. Cardiopulmonary exercise testing (CPET) can identify causes of exercise limitation. Forty-four consecutive SCD patients (27 HbSS, 11 HbSC, and 6 HbS-beta thalassemia) with a median age (interquartile range) of 26 (21-41) years underwent pulmonary function tests, CPET, chest x-ray, and echocardiography to further characterize exercise limitation in SCD. Peak oxygen uptake (V'O2 -peak), expressing maximum exercise capacity, was decreased in 83% of the studied patients. V'O2 -peak correlated with hemoglobin levels (R = 0.440, P = 0.005), forced vital capacity (FVC) (R = 0.717, P anemia (n = 17), cardiovascular dysfunction (n = 2), musculoskeletal function (n = 10), pulmonary ventilatory abnormalities (n = 1), pulmonary vascular exercise limitation (n = 1), and poor effort (n = 3). In the present study we demonstrate that anemia is the most important determinant of reduced exercise tolerance observed in SCD patients without signs of pulmonary hypertension. We found a strong correlation between various parameters of lung volume and cardiothoracic ratio and we hypothesize that cardiomegaly and relative small chest size may be important causes of the impairment in pulmonary function, that is, reduced long volumes and diffusion capacity, in SCD. Taking into account anthropomorphic differences between SCD patients and controls could help to interpret lung function studies in SCD better.

  14. Detection of Rare Beta Globin Gene Mutations in Northwestern Iran

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    M Haghi


    Full Text Available Introduction: Recent molecular studies on Iranian β-thalassemia genes revealed the presence of eight common mutations associated with thalassemia. Although these mutations are frequent, there are other rare and unknown mutations that can create large problems in designing preventive programs. We detected and explained the common mutations in north-western Iran previously and detection of the rare and unknown mutations could be useful in diagnosis and design of future preventive programs. Methods: In this study, 5ml peripheral blood from 20 Azari- β-thalassemia patients whose mutation was not revealed in the previous study was collected and DNA extraction was done by isopropanol and proteinase k method. Initially, samples were examined for the rare mutations: Codon6, Codon16, Codon41/42, Codon36/37, -88 and Codon22 by ARMS – PCR techniques and then the unknown cases were directly sequenced. Results: According to our results, Codon15(TGG-TGA, Codon16(-C, Codon36/37(-T, IVSII-848(C-A, IVSII-745(C-G, -28(A-C( and Codon25/26(+T were recognized and added to the spectrom of beta globin gene mutations in Azerbaijan and Iran. Also, we detected four SNP sites: 5’UTR+20(C-T, Codon2 (CAC-CAT , IVSII-16(C-G and IVSII-666(T-C in β-thalassemia genes. Conclusion: Our results could be useful for developing molecular screening plans and help prenatal diagnosis of beta thalassemia in Azerbaijan , Iran and other neighboring countries.

  15. Implications of the genetic epidemiology of globin haplotypes linked to the sickle cell gene in southern Iran. (United States)

    Rahimi, Zohreh; Merat, Ahmad; Gerard, Nathalie; Krishnamoorthy, Rajagopal; Nagel, Ronald L


    To determine the origin of sickle cell mutation in different ethnic groups living in southern Iran, we studied the haplotype background of the betaS and betaA genes in subjects from the provinces of Fars, Khuzestan, Bushehr, Hormozgan, and Kerman and from the islands of Khark and Qeshm. beta-globin gene cluster haplotypes were determined using the PCR-RFLP technique. Detection of -alpha 3.7 deletion and beta-thalassemia mutations were defined by PCR and reverse dot blot techniques, respectively. The framework of the beta-globin gene was determined using denaturing gradient gel electrophoresis. We found that the betaS mutation in southern Iran is associated with multiple mutational events. Most of the patients were from two ethnic groups: Farsi speakers (presumably Persian in origin) from Fars province and patients of Arab origin from Khuzestan province. In both ethnic groups the Arab-Indian haplotype was the most prevalent. The frequencies of the Arab-Indian and African haplotypes in sickle cell anemia patients from the provinces of Fars and Khuzestan were similar. Among betaA chromosomes the Bantu A2 haplotype was the most prevalent. The decrease in alpha-globin production in SS patients and AS individuals appeared to be related to the reduction in mean cell volume and mean cell hemoglobin. The Arab-Indian haplotype gene flow into this region of Iran can be traced to the Sassanian Empire. It is likely that the influx of betaS genes linked to the Benin and Bantu haplotypes, of African origin, must have occurred during the Arab slave trade.

  16. Laparoscopic cholecystectomy in sickle cell patients in Niger

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    Abarchi Habibou


    Full Text Available BACKGROUND: We report the results of our experience on laparoscopic cholecystectomy in sickle cell disease patients in Niger, which is included in the sickle cell belt. METHODS: A prospective study covering a period of 45 months, from July 2004 to March 2008. We included all sickle cell disease patients that underwent laparoscopic cholecystectomy. Blood transfusion was done for patients with haemoglobin (Hb levels less than 9g/dl. Homozygous and composite heterozygous patients were admitted in intensive care unit for 24 hours or plus post operatively. RESULTS:The series included 47 patients operated by the same surgeon, 31 females (66% and 16 males (34% (Ratio: 0.51. The average age was 22.4 years (range: 11 to 46 years and eleven (23.4% of them were aged less than 15 years. The types of sickle cell disease found were 37 SS, 2 SC, 1 S beta-thalassemia and 7 AS. Indications for surgery were biliary colic in 29 cases (61.7% and acute cholecystitis in 18 cases (38.3%. The mean operative time was 64 min (range: 42 to 103 min. Conversion to open cholecystectomy in 2 cases (4.2 % for non recognition of Calot‘s triangle structures. The postoperative complications were: four (4 cases of vaso-occlusive crisis and one case of acute chest syndrome. The mean postoperative hospital stay was 3,5days (range: 1 to 9 days. No mortality was encountered. CONCLUSION: Laparoscopic cholecystectomy is a safe procedure in sickle cell patients. It should be a multidisciplinary approach and involve a haematologist, an anaesthesiologist and a surgeon.

  17. The Hematopoietic Stem Cell Therapy for Exploration of Space (United States)

    Roach, Allana Nicole; Brezo, Jelena


    Astronauts experience severe/invasive disorders caused by space environments. These include hematological/cardiac abnormalities, bone and muscle losses, immunodeficiency, neurological disorders and cancer. While the cause of these symptoms are not yet fully delineated, one possible explanation could be the inhibition of hematopoietic stem cell (HSC) growth and hematopoiesis in space. HSCs differentiate into all types of blood cells, and growing evidence indicates that the HSCs also have the ability to transdifferentiate to various tissues, including muscle, skin, liver, neuronal cells and possibly bone. Therefore, a hypothesis was advanced in this laboratory that the hematopoietic stem cell-based therapy, herein called the hematopoietic stem cell therapy (HSCT), could mitigate some of the disorders described above. Due to the magnitude of this project our laboratory has subdivided it into 3 sections: a) HSCT for space anemia; b) HSCT for muscle and bone losses; and c) HSCT for immunodeficiency. Toward developing the HSCT protocol for space anemia, the HSC transplantation procedure was established using a mouse model of beta thalassemia. In addition, the NASA Rotating Wall Vessel (RWV) culture system was used to grow HSCs in space condition. To investigate the HSCT for muscle loss and bone loss, donor HSCs were genetically marked either by transfecting the beta-galactosidase-containing plasmid, pCMV.SPORT-beta-gal or by preparing from b-galactosidase transgenic mice. The transdifferentiation of HSCs to muscle is traced by the reporter gene expression in the hindlimb suspended mice with some positive outcome, as studied by the X-gal staining procedure. The possible structural contribution of HSCs against muscle loss is being investigated histochemically.

  18. High incidence of severe cyclosporine neurotoxicity in children affected by haemoglobinopaties undergoing myeloablative haematopoietic stem cell transplantation: early diagnosis and prompt intervention ameliorates neurological outcome

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    Minicucci Fabio


    Full Text Available Abstract Background Neurotoxicity is a recognized complication of cyclosporine A (CSA treatment. The incidence of severe CSA-related neurological complications following hematopoietic stem cell transplantation (HSCT is 4-11%. Methods We describe 6 cases of CSA related neurotoxicity out of 67 matched related HSCT performed in paediatric Middle East patients affected by haemoglobinopaties (5 beta thalassemia major, 1 sickle cell disease-SCD. Conditioning regimen consisted of iv busulphan, cyclophosphamide and graft-versus-host-disease (GvHD prophylaxis with CSA, methylprednisolone, methotrexate and ATG. Results All 6 patients presented prodromes such as arterial hypertension, headache, visual disturbances and vomiting, one to two days before overt CSA neurotoxicity. CSA neurotoxicity consisted of generalized seizures, signs of endocranial hypertension and visual disturbances at a median day of onset of 11 days after HSCT (range +1 to +40. Brain magnetic resonance imaging (MRI performed in all subjects showed reversible leukoencephalopathy predominantly in the posterior regions of the brain (PRES in 5/6 patients. EEG performed in 5/6 patients was always abnormal. Neurotoxicity was not explainable by high CSA blood levels, as all patients had CSA in the therapeutic range with a median of 178 ng/ml (range 69-250. CSA was promptly stopped and switched to tacrolimus with disappearance of clinical and radiological findings. All patients are symptoms-free at a median follow up of 882 days (range 60-1065. Conclusions Our experience suggests that paediatric patients with haemoglobinopaties have a high incidence of CSA related neurological events with no correlation between serum CSA levels and neurotoxicity. Prognosis is good following CSA removal. Specific prodromes such as arterial hypertension, headache or visual disturbances occurring in the early post-transplant period should be carefully evaluated with electrophysiological and MRI-based imaging in

  19. Efficacy of curcuminoids in alleviation of iron overload and lipid peroxidation in thalassemic mice. (United States)

    Thephinlap, C; Phisalaphong, C; Fucharoen, S; Porter, J B; Srichairatanakool, S


    Non-transferrin bound iron (NTBI) is detectable in plasma of beta-thalassemia patients and participates in free-radical formation and oxidative tissue damage. Desferrioxamine (DFO), deferiprone (DFP) and deferasirox (DFX) are iron chelators used for treatment of iron overload; however they may cause adverse effects. Curcuminoids (CUR) exhibits many pharmacological activities and presents beta-diketone group to bind metal ions. Iron-chelating capacity of CUR was investigated in thalassemic mice. The mice (C57BL/6 stain); wild type ((mu)beta(+/+)) and heterozygous beta-knockout ((mu)beta(th-3/+)) were fed with ferrocene-supplemented diet for 2 months, and coincidently intervened with CUR (200 mg/kg/day) and DFP (50 mg/kg/day). Plasma NTBI was quantified using NTA chelation/HPLC method, and MDA concentration was analyzed by TBARS-based HPLC. Hepatic iron content (HIC) and total glutathione concentration were measured colorimetrically. Tissue iron accumulation was determined by Perl's staining. Ferrocene-supplemented diet induced occurrence of NTBI in plasma of thalassemic mice as well as markedly increased iron deposition in spleen and liver. Treatment with CUR and DFP decreased levels of the NTBI and MDA effectively. Hepatic MDA and nonheme iron content was also decreased in liver of the treated mice whilst total glutathione levels were increased. Importantly, the CUR and DFP reduced liver weight index and iron accumulation. Clearly, CUR is effective in chelation of plasma NTBI in iron-loaded thalassemic mice. Consequently, it can alleviate iron toxicity and harmfulness of free radicals. In prospective, efficacy of curcumin in removal of labile iron pool (LIP) in hepatocytes and cardiomyocytes are essential for investigation.

  20. Chorionic Villus Sampling and Marked Membrane Separation

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    Sh. Akhlaghpoor


    Full Text Available Background/Objective: The major concern about the invasive prenatal diagnostic tests is the"nfrequency of procedure induced pregnancy loss. Chorionic Villus Sampling (CVS is the invasive"ntest of choice in the first trimester after the 10th gestational week. Our experience suggests"nmarked chorioamniotic separation is an uncommon finding after the 10th gestational week. This"nstudy assesses the rate of marked membrane separation in a 10 to 14-week gestational period"nand its effect on post CVS fetal loss."nPatients and Methods: Forty-one patients (5.2% were selected among 782 patients as cases"nwith marked membrane separation (mean maternal age, 26.9 years. CVS procedures were"nperformed with a 20-gauge Chiba needle attached to a 20-ml syringe under ultrasound guidance."nFollow-up was performed by phone call and clinical visits until 24 weeks of gestation. For the"ncontrol group, the follow-up was performed for only 2 weeks. Early fetal loss in the first two"nweeks of post procedural period, and late fetal loss from 2 weeks after procedure till the 24th"ngestational week were considered as CVS complications."nResults: We detected 2.4% early fetal losses after the procedure. Fourteen cases voluntarily"nunderwent therapeutic abortion due to beta-thalassemia or hemophilia. One fetus with"nmicrocephaly was spontaneously aborted in the 21st gestational week. Twenty-five neonates"nwere delivered alive at term and one prematurely at the 32nd week. Marked membrane separation"nhad no significant effect on early post CVS fetal loss rate."nConclusion: The procedure does not have a major impact on the early post CVS fetal loss in"npatients with marked membrane separation.

  1. Determining and surveying the role of carnitine and folic acid to decrease fatigue in β-thalassemia minor subjects. (United States)

    Tabei, Seyed Mohammad Bagher; Mazloom, Maryam; Shahriari, Mahdi; Zareifar, Soheila; Azimi, Ali; Hadaegh, Amirhossein; Karimi, Mehran


    Beta-thalassemia minor (BTM) patients usually experience fatigue, bone pain complaint, and muscle weakness. Carnitine is an essential protein for transportation of long-chain fatty acids to the matrix for beta-oxidation. BTM patients have abnormally low plasma carnitine concentrations, which results in deficient ATP production. Carnitine and folic acid together may have a role in preventing bone pain complaint and fatigue in these patients. The aim of this study is to determine the effect of carnitine and folic acid supplementation in subjects with BTM. Seventy three BTM (mean age 11.06 ± 5.46 years) and 23 healthy controls (mean age 8.48 ± 3.78 years) were enrolled in the study. Fasting blood was drawn to determine baseline free and total carnitine levels, red blood cell folate concentration, and hemoglobin level. BTM were divided into three groups and received different types of supplementation for 3 months: Group 1, 50 mg/kg/day carnitine; Group 2, 50 mg/kg/day carnitine plus 1 mg/day folic acid; and Group 3, 1 mg/day folic acid. Controls did not receive supplementation. Laboratory parameters were again evaluated after 3 months' supplementation. A detailed quality of life questionnaire was designed to investigate muscle symptoms before and after supplementation. Free and total plasma carnitine concentration and hemoglobin levels in BTM subjects increased significantly after carnitine supplementation (P carnitine. Red blood cell folate level increased after folic acid supplementation. Carnitine and folic acid supplementation resulted in a decrease in bone pain complaint and muscle weakness in cases with β-thalassemia minor.

  2. Modified port placement and pedicle first approach for laparoscopic concomitant cholecystectomy and splenectomy in children

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    Pal Kamalesh


    Full Text Available Aim : Laparoscopy is becoming the preferred modality for concomitant cholecystectomy and splenectomy (CAS. Usually, six to seven ports are employed for CAS, and spleen is removed by classical lateral approach or anterior approach. We report here our modified five-port and pedicle first approach for CAS in children to minimize the intraoperative bleeding and maximize the access. Materials and Methods : Twenty-one children underwent laparoscopic CAS with this new approach and their data were recorded prospectively. Following cholecystectomy (with ports 1-4, left side was elevated by 30°. The spleen was lifted by a grasper/fan retractor through port no. 5. The pedicle was dissected and splenic vessels were divided by ligasure (vessels < 8 mm, and for bulkier pedicle, vascular endo-GIA stapler was used. Short gastric and gastrosplenic ligament, lower pole and phrenico-colic attachments and upper pole attachments were dissected by ligasure in that sequence. Spleen was placed in endosac and delivered by digital fracture technique. Occasionally, lower transverse incision was made to deliver a massive spleen. Results : There were 12 males and 9 females with an average age of 8 years. Fourteen had sickle cell disease (SCD and 7 had SCD and beta thalassemia. All CAS were completed successfully without any complication. Total duration was 160 minutes. Cholecystectomy took an average of 35 minutes. Average blood loss was 140 ml. The mean splenic weight was 900 g and mean length was 20 cm. Duration of hospitalization was 3-4 days. Conclusion : CAS can be successfully performed by five ports. The pedicle first approach is extremely helpful in moderate to massive spleens as it reduces splenic size, vascularity and bleeding from capsular adhesions or inadvertant lacerations.

  3. Análise quantitativa e molecular de hemoglobina fetal em indivíduos da população brasileira Quantitative and molecular analysis of fetal hemoglobin in individuals from the Brazilian population

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    Paula J. A. Zamaro


    eletroforese e observou-se média de 32,28% para desnaturação alcalina e de 26,4% para HPLC. As análises moleculares por PCR-ASO foram realizadas na tentativa de se identificar um defeito genético que pudesse explicar o aumento de Hb F, pelo rastreamento de 16 mutações que originam talassemias do tipo beta. Encontraram-se 5,3% de heterozigotos para mutação CD6-A e 1,75% para as mutações CD 39, IVS1:6, -87 e IVS2:654, todas em heterozigose. Os resultados encontrados neste estudo evidenciam a necessidade de melhor caracterização dos perfis de hemoglobina obtidos pelos métodos clássicos e a importância de sua caracterização molecular.The fetal hemoglobin, Hb F, formed by two alpha and two gamma globin chains, is characteristic of the fetal development period and has diminished synthesis in the post-natal period. In some hereditary alterations Hb F remains elevated, as in delta-beta thalassemia, beta thalassemia and hereditary persistence of Hb F (HPFH. The synthesis of gamma globin can also be stimulated by external factors including leukemia, blood marrow transplantation and chemical induction, amongst others. Through the observation of elevated levels of Hb F in blood samples using electrophoretic procedures, we aimed at evaluating the amount of Hb F in blood donor samples in order to establish limits of normality in the population from São José do Rio Preto and region. Also using alkaline denaturation and high-pressure liquid chromatography (HPLC, we compared the applied methodologies and, in individuals with increased Hb F, we used molecular studies to identify mutations that modify the gamma globin gene expression. Blood samples from 119 donation candidates and, as a control group, 89 from individuals without symptoms of anemia or hematological findings and with increased Hb F, were analyzed. Of these 119 samples from blood donation candidates, 110 were used to trace the profile of normal Hb F, comparing the applied measurement methodologies, giving an

  4. Nutrition assessment in children with sickle cell disease. (United States)

    Williams, R; George, E O; Wang, W


    Children with sickle cell disease have decreased height and weight when compared with their peers. Although exact reasons for poor growth have not been established, increased calorie and protein needs and deficiencies in zinc, folic acid, and vitamins A, C, and E may be factors. To determine whether inadequate nutrient intake contributes to this poor growth, we conducted a survey of the nutrition knowledge and practices of families affected by sickle cell disease. Sixty-one patients with a median age of 8 years (range, 13 months to 17 years) participated in the study. Patients with homozygous S hemoglobin (sickle cell) disease (Hb SS, n = 34) and sickle beta zero thalassemia (Hb S beta zero-thalassemia, n = 2) were combined; 19% were below the fifth percentile for height. The other patients, with sickle hemoglobin C disease (Hb SC, n = 21) and sickle beta plus thalassemia (Hb beta(+)-thalassemia, n = 4), were grouped, and 4% were below the fifth percentile for height (P = .043). Ninety percent of the study patients or their parents were familiar with the food groups indicated on the US Department of Agriculture's Food Guide Pyramid, but most patients failed to consume appropriate amounts from those groups. Although two thirds of the patients ate the recommended number of servings daily from the meat group, only 20% to 31% of the recommended servings from each of the other food groups was consumed. This was possibly related to low socioeconomic status. The patients in the Hb SS group ate significantly less from the bread (P group. Fifty-nine percent of families had incomes below the poverty level, and 79% participated in a food assistance program. We conclude that the nutrient intake of patients with sickle cell disease is often inadequate. Education for patients with sickle cell disease should focus on (1) specific nutrient needs, with proper distribution of dietary intake among the food groups, (2) ways to provide nutritious meals on a limited income, and (3

  5. A strategy analysis for genetic association studies with known inbreeding

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    del Giacco Stefano


    Full Text Available Abstract Background Association studies consist in identifying the genetic variants which are related to a specific disease through the use of statistical multiple hypothesis testing or segregation analysis in pedigrees. This type of studies has been very successful in the case of Mendelian monogenic disorders while it has been less successful in identifying genetic variants related to complex diseases where the insurgence depends on the interactions between different genes and the environment. The current technology allows to genotype more than a million of markers and this number has been rapidly increasing in the last years with the imputation based on templates sets and whole genome sequencing. This type of data introduces a great amount of noise in the statistical analysis and usually requires a great number of samples. Current methods seldom take into account gene-gene and gene-environment interactions which are fundamental especially in complex diseases. In this paper we propose to use a non-parametric additive model to detect the genetic variants related to diseases which accounts for interactions of unknown order. Although this is not new to the current literature, we show that in an isolated population, where the most related subjects share also most of their genetic code, the use of additive models may be improved if the available genealogical tree is taken into account. Specifically, we form a sample of cases and controls with the highest inbreeding by means of the Hungarian method, and estimate the set of genes/environmental variables, associated with the disease, by means of Random Forest. Results We have evidence, from statistical theory, simulations and two applications, that we build a suitable procedure to eliminate stratification between cases and controls and that it also has enough precision in identifying genetic variants responsible for a disease. This procedure has been successfully used for the beta-thalassemia, which is

  6. Primary stroke prevention for sickle cell disease in north-east Italy: the role of ethnic issues in establishing a Transcranial Doppler screening program

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    Pierobon Marta


    Full Text Available Abstract Background Stroke is a serious complication of sickle cell disease (SCD in children. Transcranic Doppler (TCD is a well-established predictor of future cerebrovascular symptoms: a blood flow velocity >200 cm/sec in the Middle Cerebral Artery (MCA correlates with a high risk of stroke in cohorts of African-american HbS/HbS patients. In North-East Italy the recent increase in SCD patients is mainly due to immigration from Africa. A comprehensive care program for children with SCD was established in our Center since 2004, but a wide and routine screening for Primary stroke prevention needs to be developed. Methods In order to verify the feasibility of TCD and Transcranial color coded Sonography (TCCS screening in our setting and the applicability of international reference values of blood velocities to our population of African immigrants with HbS/HbS SCD, we performed TCD and TCCD in 12 HbS/HbS African children and two groups of age-matched controls of Caucasian and African origin respectively. TCD and TCCS were performed on the same day of the scheduled routine hematologic visit after parental education. Results All parents accepted to perform the sonography to their children. TCD and TCCD were performed in all patients and an adequate temporal window could be obtained in all of them. Pulsatility index and depth values in both the MCA and the Basilar Artery (BA were similar at TCD and TCCS evaluation in the three groups while time-average maximum velocities (TAMM, peak systolic velocity and diastolic velocity in the MCA and BA were higher in the patients' group on both TCD and TCCS evaluation. African and Caucasian healthy controls had similar lower values. Conclusion Our preliminary data set the base to further evaluate the implementation of a primary stroke prevention program in our setting of HbS/HbS African immigrants and HbS/beta thalassemia Italians. Parental education-preferably in the native language- on stroke risk and

  7. Healthcare, molecular tools and applied genome research. (United States)

    Groves, M


    Biotechnology 2000 offered a rare opportunity for scientists from academia and industry to present and discuss data in fields as diverse as environmental biotechnology and applied genome research. The healthcare section of the meeting encompassed a number of gene therapy delivery systems that are successfully treating genetic disorders. Beta-thalassemia is being corrected in mice by continous erythropoeitin delivery from engineered muscles cells, and from naked DNA electrotransfer into muscles, as described by Dr JM Heard (Institut Pasteur, Paris, France). Dr Reszka (Max-Delbrueck-Centrum fuer Molekulare Medizin, Berlin, Germany), meanwhile, described a treatment for liver metastasis in the form of a drug carrier emolization system, DCES (Max-Delbrueck-Centrum fuer Molekulare Medizin), composed of surface modified liposomes and a substance for chemo-occlusion, which drastically reduces the blood supply to the tumor and promotes apoptosis, necrosis and antiangiogenesis. In the molecular tools section, Willem Stemmer (Maxygen Inc, Redwood City, CA, USA) gave an insight into the importance that techniques, such as molecular breeding (DNA shuffling), have in the evolution of molecules with improved function, over a range of fields including pharmaceuticals, vaccines, agriculture and chemicals. Technologies, such as ribosome display, which can incorporate the evolution and the specific enrichment of proteins/peptides in cycles of selection, could play an enormous role in the production of novel therapeutics and diagnostics in future years, as explained by Andreas Plückthun (Institute of Biochemistry, University of Zurich, Switzerland). Applied genome research offered technologies, such as the 'in vitro expression cloning', described by Dr Zwick (Promega Corp, Madison, WI, USA), are providing a functional analysis for the overwhelming flow of data emerging from high-throughput sequencing of genomes and from high-density gene expression microarrays (DNA chips). The

  8. Factors regulating Hb F synthesis in thalassemic diseases

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    Lerone Maria


    Full Text Available Abstract Background The thalassemic syndromes originate from mutations of the globin genes that cause, besides the characteristic clinical picture, also an increased Hb F amount. It is not yet clear if there are more factors, besides the beta globin genotype, determining the Hb F production. We have tried to find out if there are relations between total Hb and Hb F, between erythropoietin (Epo and Hb F, between Hb F and point mutations of the gamma gene promoters. Materials and Methods Hematologic parameters, iron status, alpha/non-alpha globin ratio, Epo level, and thalassemic defects of the alpha-, beta-, and gamma-globin genes were explored using standard methods in patients affected by thalassemic diseases. Ninety-five non thalassemic individuals have been examined as controls. Results Two clinical variants of beta-thalassemia intermedia referred to as beta-thal int sub-silent and evident are associated with distinct sets of mutations of the beta-globin gene. Silent beta thal mutations are invariably associated with sub-silent beta thal int; beta° or severe beta+ thal mutations are associated with evident beta thal int (88% and almost invariably (98% with thalassemia major. A positive correlation was observed between the severity of the disease and the Hb F level, but no correlation was found between the Hb F and erythropoietin (Epo level. The mutation Ggamma -158 C→T was detected in 26.9% of patients affected by beta-thal int sub-silent and evident, respectively, but only in 2% of patients with thalassemia major. Conclusions The severity of beta-thal int and the increased Hb F level are strictly dependent from the type of beta-globin gene mutations. No relation is found between Hb F synthesis and Epo secretion. The mutation Ggamma -158 C→T, common among patients affected by beta-thal int and very rare in thal major patients, does not seem, in this study, to influence the Hb F content in beta thal int patients.

  9. 广西贵港地区地中海贫血高风险人群的发病率及基因检测%Incidence and genetic test of thalassemia among high-risk population in Guigang City

    Institute of Scientific and Technical Information of China (English)

    李燕; 吴汉锋; 钟伟明


    Objective To analyze the incidence and genetic distribution of thalassemia among high-risk population in Guigang City of Guangxi Province,and provide the basis for the prevention the born of severe babies with thalassemia. Methods Among 342 high-risk people with thalassemia from January 2011 to June 2011, a detection gene were detected with gap-PCR,and RDB were applied for the detection of three alpha thalassemia point mutations and 17 kinds of beta thalassemia. Results The total detection rate was 80.99% with 167 alpha thalassemia cases, 101 beta Mediterranean anemia cases,9 double heterozygous cases. Conclusion Thalassemia is highly prevalent in Guangxi,therefore,genetic detection can enhance the detection rate of thalassemia and it is essentially conducive to giving sound child birth and reducing the birth of thalsssemia child.%目的 研究广西贵港地区地中海贫血高风险人群的发病率及基因分布,为预防地中海贫血重症患儿的出生、减少出生缺陷及提高人口素质服务.方法 2011年1月~2011年6月期间,对具有地中海贫血高风险的342人,应用单管多重PCR技术进行α缺失型基因检测以及反向点杂交法检测中国人常见的三种α-地中海贫血点突变和中国人常见的17种β-地中海贫血.结果 342人中检出α-地中海贫血167例,β-地中海贫血101例,α和β地贫双重杂合子9例,检出率为80.99%.结论 广西是地中海贫血高发区,应用基因诊断,有效地提高地中海贫血的检出率,对优生优育、干预重症地贫儿出生有着重要作用.


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    Athanasios Aessopos


    Full Text Available Heart disease is the leading cause of mortality and one of the main causes of morbidity in beta-thalassemia. Patients with homozygous thalassemia may have either a severe phenotype which is usually transfusion dependent or a milder form that is thalassemia intermedia.  The two main factors that determine cardiac disease in homozygous β thalassemia are the high output state that results from chronic tissue hypoxia, hypoxia-induced compensatory reactions and iron overload.  The high output state playing a major role in thalassaemia intermedia and the iron load being more significant in the major form. Arrhythmias, vascular involvement that leads to an increased pulmonary vascular resistance and an increased systemic vascular stiffness and valvular abnormalities also contribute to the cardiac dysfunction in varying degrees according to the severity of the phenotype.  Endocrine abnormalities, infections, renal function and medications can also play a role in the overall cardiac function.  For thalassaemia major, regular and adequate blood transfusions and iron chelation therapy are the mainstays of management. The approach to thalassaemia intermedia, today, is aimed at monitoring for complications and initiating, timely, regular transfusions and/or iron chelation therapy.  Once the patients are on transfusions, then they should be managed in the same way as the thalassaemia major patients.  If cardiac manifestations of dysfunction are present in either form of thalassaemia, high pre transfusion Hb levels need to be maintained in order to reduce cardiac output and appropriate intensive chelation therapy needs to be instituted.  In general recommendations on chelation, today, are usually made according to the Cardiac Magnetic Resonance findings, if available.  With the advances in the latter technology and the ability to tailor chelation therapy according to the MRI findings as well as the availability of three iron chelators, together with

  11. Total beta-globin gene deletion has high frequency in Filipinos

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    Patrick, N.; Miyakawa, F.; Hunt, J.A. [Univ. of Hawaii, Honolulu, HI (United States)] [and others


    The distribution of {beta}-thalassemia [{beta}{sup Th}] mutations is unique to each ethnic group. Most mutations affect one or a few bases; large deletions have been rare. Among families screened in Hawaii, [{beta}{sup Th}] heterozygotes were diagnosed by microcytosis, absence of abnormal hemoglobins on isoelectric focusing, and raised Hb A{sub 2} by chromatography. Gene frequency for {beta}{sup Th} was 0.02 in Filipinos. In Filipinos, polymerase chain reaction [PCR] with denaturing gradient gel electrophoresis for {beta}{sup Th} mutations detected a mutation in only 6 of 42 {beta}{sup Th} heterozygotes; an IVS2-666 C/T polymorphism showed non-heterozygosity in 37 and heterozygosity in only 5 of these {beta}{sup Th} heterozygotes. One {beta}{sup Th}/{beta}{sup Th} major patient and his mother had no mutation detected by allele-specific oligomer hybridization; PCR failed to amplify any DNA from his {beta}-globin gene. After a total {beta}-globin gene deletion [{beta}{sup Del}] was found in a Filipino family in Ontario, specific PCR amplification for {beta}{sup Del} detected this in 43 of 53 {beta}{sup Th} Filipino samples tested; the above {beta}{sup Th}/{beta}{sup Th} patient was a ({beta}{sup Del}/{beta}{sup Del}) homozygote. The {beta}{sup Del} may account for over 60% of all {beta}{sup Th} alleles in Filipinos; this is the highest proportion of a deletion {beta}{sup Th} mutation reported from any population. Most but not all {beta}{sup Del} heterozygotes had high Hb F [5.13 {plus_minus} 3.94 mean {plus_minus} 1 s.d.] compared to the codon 41/42 four base deletion common in Chinese [2.30 {plus_minus} 0.86], or to {beta}{sup Th} heterozygotes with normal {alpha}-globin genes [2.23 {plus_minus} 0.80].

  12. Mapping the health indicators of Chhattisgarh: A public health perspective

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    Abhiruchi Galhotra


    Full Text Available Introduction: The state of Chhattisgarh today faces several challenges in improving the health status of its people. The on-going problems of maternal and child mortality, communicable diseases, and HIV/AIDS pandemic still need greater interventions/support from the already overburdened health systems. In addition, the public health challenges include the escalating burden of chronic noncommunicable diseases. Keeping all these things in mind a study was carried out to have an overview of the public health scenario of Chhattisgarh. Aim: This paper aims to review the different public health indicators of Chhattisgarh. Materials and Methods: This study comprised of reviewing different health indicators of Chhattisgarh adopting three different methods during the period March-April 2013. The methods were: (i extensive online search, (ii reviewing the related literatures from different journals and other authentic printed materials, and (iii information collected from public health experts through e-mail, telephone, or direct interaction. Results: Out of 2.55 crore populations in the state (as per Census 2011, 78% lives in rural areas and 37% of the population is tribal. The sex ratio is 968 and the literacy rate is 65.5% in population above 7 years of age. There is a shortage of trained health care providers in Chhattisgarh. The crude birth rate is 23.5 per 1000 (population Annual Health Survey [AHS] 2011-2012. The infant mortality rate is 48 per 1000 live births (SRS 2012. Malnutrition, anemia, sickle cell hemoglobinopathy, Beta thalassemia trait, and G6 PD enzyme deficiency are very high among the tribes of Chhattisgarh. Malaria has been a major health problem. Chhattisgarh is one of the states with annual parasite index >5 (MRC report. The other states are Rajasthan, Gujarat, Karnataka, Goa, Southern Madhya Pradesh, Jharkhand, Odisha, and Northeastern states. Conclusion: From a public health point of view, most of the health indicators are below

  13. Longitudinal Study on Liver Functions in Patients with Thalassemia Major before and after Deferasirox (DFX) Therapy (United States)

    Soliman, Ashraf; Yassin, Mohamed; Al Yafei, Fawzia; Al-Naimi, Lolwa; Almarri, Noora; Sabt, Aml; De Sanctis, Vincenzo


    By performing regular blood transfusion and iron chelation therapy, most patients with beta thalassemia major (BTM) now survive beyond the third decade of life. Liver disease is becoming an important cause of morbidity and mortality in these patients. Chronic hepatitis and/or severe iron overload are both important causes of liver pathology. Iron chelation with desferrioxamine (DFO) reduces excessive body iron, but its efficacy is limited by poor compliance and dose related toxicity. The recent use of Deferasirox ( DFX ), an oral single dose therapy, has improved the compliance to chelation. Aims To study the long-term liver functions in BMT patients, seronegative for liver infections before versus after DFX treatment in relation to ferritin level. Methods Only BTM patients with hepatitis negative screening (checked every year) and on treatment with DFO for at least five years and with DFX for four years were enrolled. Liver function tests including serum bilirubin, alanine transferase (ALT), aspartate transferase (AST), albumin, insulin-like growth factor – I (IGF-I) and serum ferritin concentrations were followed every six months in 40 patients with BTM. Results DFX treatment (20 mg/kg/day) significantly decreased serum ferritin level in patients with BTM; this was associated with a significant decrease in serum ALT, AST, ALP and increase in IGF-I concentrations. Albumin concentrations did not change after DFX treatment. ALT and AST levels were correlated significantly with serum ferritin concentrations ( r = 0.45 and 0.33 respectively, p < 0.05). IGF-I concentrations were correlated significantly with serum ALT (r= 0.26, p = 0.05) but not with AST, ALP, bilirubin or albumin levels. The negative correlation between serum ferritin concentrations and ALT suggests that the impairment of hepatic function negatively affect IGF-I synthesis in these patients due to iron toxicity, even in the absence of hepatitis. Conclusions Some impairment of liver function can occur

  14. Thalassemic osteopathy: a new marker of bone deposition. (United States)

    Baldini, M; Forti, S; Orsatti, A; Marcon, A; Ulivieri, F M; Airaghi, L; Zanaboni, L; Cappellini, M D


    Osteopathy represents a prominent cause of morbidity in patients with beta-thalassemia major (TM) and manifests as osteopenia/osteoporosis. Biochemical turnover markers (BTMs) are considered a useful, non-invasive tool for the clinical follow-up of osteoporotic patients; they can provide a dynamic view of the remodeling process and give information on the metabolic activity of bone tissue as well as on the pathogenesis of bone loss. The amino-terminal pro-peptide of type I procollagen (P1NP) is a recently introduced marker that is considered the most sensitive index of bone formation. Although demonstrated in several categories of patients with bone disease, there is little information on the clinical usefulness of this bone formation index in thalassemic patients. We evaluated the P1NP levels of 53 adult patients with b-thalassemia major (21 males and 32 females, mean age 34.5 ± 5.7, range 22-46 years) and associated osteopathy. We investigated the correlation between P1NP and bone condition as examined by dual X-ray photon absorptiometry and with BTMs expressing bone resorption and bone mineralization (carboxyterminal collagen cross-linked (CTX) terminal regions of type I collagen and osteocalcin, respectively). P1NP serum levels were correlated with CTX levels (r=0.545, p<0.001); the results were unchanged when males and females, as well as osteoporotic and osteopenic subgroups, were considered separately. No correlation was demonstrated neither between OC and CTX (r=0.17, p=ns), nor between P1NP and OC levels (r=0.11, p=ns). No correlation was demonstrated among the P1NP/CTX ratio and age, OC or densitometric values and no difference was found in the same ratio between osteopenic (0.19 ± 0.16) and osteoporotic (0.15 ± 0.14) patients. Similar results were obtained for the OC/CTX ratio, as it was not correlated with age, P1NP or densitometric values. This is the first report of circulating P1NP in patients with TM-associated osteoporosis. P1NP and CTX assays

  15. Genetic/metabolic effect of iron metabolism and rare anemias

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    Clara Camaschella


    Full Text Available Advances in iron metabolism have allowed a novel classification of iron disorders and to identify previously unknown diseases. These disorders include genetic iron overload (hemochromatosis and inherited iron-related anemias, in some cases accompanied by iron overload. Rare inherited anemias may affect the hepcidin pathway, iron absorption, transport, utilization and recycling. Among the genetic iron-related anemias the most common form is likely the iron-refractory iron-deficiency anemia (IRIDA, due to mutations of the hepcidin inhibitor TMPRSS6 encoding the serine protease matriptase-2. IRIDA is characterized by hepcidin up-regulation, decrease iron absorption and macrophage recycling and by microcytic- hypochromic anemia, unresponsive to oral iron. High serum hepcidin levels may suggest the diagnosis, which requires demonstrating the causal TMPRSS6 mutations by gene sequencing. Other rare microcytic hypochromic anemias associated with defects of iron transport-uptake are the rare hypotransferrinemia, and DMT1 and STEAP3 mutations. The degree of anemia is variable and accompanied by secondary iron overload even in the absence of blood transfusions. This is due to the iron-deficient or expanded erythropoiesis that inhibits hepcidin transcription, increases iron absorption, through the erythroid regulator, as in untransfused beta-thalassemia. Sideroblastic anemias are due to decreased mitochondrial iron utilization for heme or sulfur cluster synthesis. Their diagnosis requires demonstrating ringed sideroblasts by Perl’s staining of the bone marrow smears. The commonest X-linked form is due to deltaamino- levulinic-synthase-2-acid (ALAS2 mutations. The recessive, more severe form, affects SLC25A38, which encodes a potential mitochondrial importer of glycine, an amino acid essential for ALA synthesis and thus results in heme deficiency. Two disorders affect iron/sulfur cluster biogenesis: deficiency of the ATP-binding cassette B7 (ABCB7 causes X

  16. Hemoglobinas humanas: hipótese malária ou efeito materno? Human hemoglobins: malaria hypothesis or maternal effect?

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    Felipe R. Torres


    Full Text Available As hemoglobinopatias têm provido uma das poucas demonstrações convincentes da seleção, influenciando a freqüência de único gene na população humana. A alta taxa de desordens, tais como a anemia falciforme e a beta-talassemia, ocorridas em áreas subtropicais ou tropicais dentro do cinturão da malária, levou Haldane a propor que a malária pode ser o agente seletivo responsável que balanceia a perda dos genes para a talassemia e a anemia falciforme, por morte prematura dos homozigotos a partir do aumento do valor adaptativo de heterozigotos no ambiente com malária. Mas uma nova proposta surgiu para explicar a manutenção deste polimorfismo, baseada na fertilidade diferencial ou efeito parental. Alguns autores observaram uma distorção favorecendo a transmissão de alelos mutantes em áreas não endêmicas de malária. Com base nestas observações, esses autores propuseram um efeito materno para explicar tais distorções. Este estudo tem como objetivo apresentar uma revisão destes mecanismos envolvidos na manutenção do polimorfismo de hemoglobinopatias, desde seu modelo clássico até hipóteses alternativas que surgiram recentemente na literatura.Hemoglobinopathies are providing one of the few convincing demonstrations of selection, influencing the frequency of a single gene in the human population. The high rate of disorders, such as the sickle cell anemia and beta-thalassemia that occur in the subtropical or tropical regions within the strip affected by malaria, led Haldane to propose that malaria may be the selective agent responsible for balancing the loss of thalassemia and sickle cell anemia genes due to the early death of homozygous patients. But a new proposal appeared to explain the maintenance of these polymorphisms, based on the differential fertility or parental effect. Some authors observed a distortion favoring the transmission of mutant alleles in non-endemic malaria areas. Based on these observations, the

  17. Triagem de hemoglobinopatias em doadores de sangue de Caxias do Sul, Rio Grande do Sul, Brasil: prevalência em área de colonização italiana Screening for hemoglobinopathies in blood donors from Caxias do Sul, Rio Grande do Sul, Brazil: prevalence in an Italian colony

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    Cristina Lucia Alberti Lisot


    Full Text Available A alta prevalência de beta-talassemia em italianos e a participação dos mesmos na formação étnica da cidade de Caxias do Sul e arredores, Rio Grande do Sul, Brasil, conduziram-nos à investigação de hemoglobinopatias em uma amostra de 608 doadores de sangue do Hemocentro Regional de Caxias do Sul. Apesar da influência étnica, encontramos 1,81% de hemoglobinas anormais (0,16% Hb AC, 0,99%, Hb AS e 0,66% Hb AH, um padrão similar com o estudo do interior do Estado do Rio Grande do Sul para alterações qualitativas. Para as talassemias, as técnicas mais comuns, cruzadas com seqüenciamento de DNA, em nossas mãos, não foram capazes de esclarecer anormalidades quantitativas da hemoglobina. Esse resultado pode ser atribuído a alterações genéticas ainda não conhecidas, a limitações técnicas ou, mais simplesmente, à miscigenação.The high prevalence of beta thalassemia among Italians and their participation in the ethnic formation of Caxias do Sul, Rio Grande do Sul State, Brazil, and neighboring cities prompted us to investigate hemoglobinopathies in 608 blood donors at the Caxias do Sul Regional Blood Center. Despite the ethnic influence, abnormal hemoglobin levels were found in only 1.81% of the donors (0.16% Hb AC, 0.99% Hb AS, and 0.66% Hb AH, similar to the levels observed in a study on qualitative disorders conducted in the rural area of Rio Grande do Sul. In our setting, the most commonly used screening tests for thalassemia, combined with DNA sequencing, were unable to detect quantitative hemoglobin synthesis disorders. This may be attributable to still-unknown genetic disorders, technical limitations, or simply to miscegenation.

  18. Nanoparticles for Site Specific Genome Editing (United States)

    McNeer, Nicole Ali

    Triplex-forming peptide nucleic acids (PNAs) can be used to coordinate the recombination of short 50-60 by "donor DNA" fragments into genomic DNA, resulting in site-specific correction of genetic mutations or the introduction of advantageous genetic modifications. Site-specific gene editing in hematopoietic stem and progenitor cells (HSPCs) could result in treatment or cure of inherited disorders of the blood such as beta-thalassemia. Gene editing in HSPCs and differentiated T cells could help combat HIV/AIDs by modifying receptors, such as CCR5, necessary for R5-tropic HIV entry. However, translation of genome modification technologies to clinical practice is limited by challenges in intracellular delivery, especially in difficult-to-transfect hematolymphoid cells. In vivo gene editing could also provide novel treatment for systemic monogenic disorders such as cystic fibrosis, an autosomal recessive disorder caused by mutations in the cystic fibrosis transmembrane receptor. Here, we have engineered biodegradable nanoparticles to deliver oligonucleotides for site-specific genome editing of disease-relevant genes in human cells, with high efficiency, low toxicity, and editing of clinically relevant cell types. We designed nanoparticles to edit the human beta-globin and CCR5 genes in hematopoietic cells. We show that poly(lactic-co-glycolic acid) (PLGA) nanoparticles can delivery PNA and donor DNA for site-specific gene modification in human hematopoietic cells in vitro and in vivo in NOD-scid IL2rgammanull mice. Nanoparticles delivered by tail vein localized to hematopoietic compartments in the spleen and bone marrow of humanized mice, resulting in modification of the beta-globin and CCR5 genes. Modification frequencies ranged from 0.005 to 20% of cells depending on the organ and cell type, without detectable toxicity. This project developed highly versatile methods for delivery of therapeutics to hematolymphoid cells and hematopoietic stem cells, and will help to

  19. [Infections in Senegalese children and adolescents with sickle cell anemia: epidemiological aspects]. (United States)

    Diagne, I; Soares, G M; Gueye, A; Diagne-Gueye, N R; Fall, L; N'Diaye, O; Camara, B; Diouf, S; Fall, M


    Infection is the main factor of morbidity and mortality in children with sickle cell disease (SCD). The objective of this study is to determine it's epidemiologic outline in senegalese children and adolescents with SCD. We retrospectively studied infection data in all the charts of a cohort of 323 patients with SCD (307 SS, 13 SC and 3 s beta + thalassemia) followed at Albert Royer children hospital from january 1991 to december 1997. Serum sampling was systematically made for HIV and antigen HBs serology in all patients we received in the last 3 months (october to december 1997). Patients were aged from 5 months to 22 years (medium age = 8 years). 813 infection episodes were diagnosed, concerning 184 patients (56 per cent). SS patients were more affected (59 per cent) than the others (23 per cent, p = 0.04). ENT and broncho-pulmonary onsets were more frequent but had a generally benign course. Menigitidis, septicemia and osteomyelitis were exclusively diagnosed in SS patients. Their prevalences in this group were respectively: 1.0 per cent, 4.9 per cent and 9.8 per cent. HIV serology was determined in 155 patients, including 41 per cent with blood transfusion antecedents. All tests were negative. HBs antigen was determined in 104 patients and seroprevalence was 7.7 per cent in the whole group and 6.0 per cent in patients with transfusion antecedents and 7.7 per cent for the others. Plasmodium falciparum malaria onset was observed in 9.6 per cent of our patients and there was no case of cerebral malaria. Infection was involved in 9 of the 11 cases of death. Then infection constitute the major problem in children and adolescents with SCD in Dakar. However prevalences of severe onsets are comparable to data in Europe despite our poor follow up conditions. Senegal haplotype may lead to a good tolerance of SCD. Negative HIV serology and low HBs antigen seroprevalence in transfused patients are attributed to a relatively low level of HIV prevalence in the general

  20. Morbidity, beta S haplotype and alpha-globin gene patterns among sickle cell anemia patients in Kuwait. (United States)

    Adekile, A D; Haider, M Z


    Admission records of children with sickle cell anemia (SS), in the two main teaching hospitals in Kuwait, were reviewed for a 1-year period. The haplotypes of 92 beta s chromosomes (from 39 SS, 11 AS, 2 S beta-thalassemia [S beta-thal] and 1 SD individuals) were determined using an allele-specific oligonucleotide (ASO) hybridization technique, while the alpha-globin gene status of 27 SS and 33 AS individuals, i.e. 120 chromosomes, was determined with a combination of polymerase chain reaction and AS techniques. A vasooclusive crisis was the most common (60.0%) cause of hospitalization, followed by infections (20%). Hospital admissions were most common during the hottest month of the year (July). Few complications of the disease were seen among patients on follow-up; however, splenomegaly was present in 24.0%, hepatomegaly in 15.2%, gallstones in 15.2% and aseptic necrosis of the femoral head in 6.1%. Haplotype 31 (Saudi Arabia/India) is the most frequent in this community, being present in 80.4% of the chromosomes tested; Benin haplotype 19 was found in 12.0% and Bantu haplotype 20 in 6.5%. Hb F in the haplotype 31 homozygotes and heterozygotes ranged from 11.4 to 35.1% (mean 22.5 +/- 5.2%). The frequency of alpha-thal determinants in the study was 40.0%, the commonest being the -alpha 3.7-kb deletion (27.5%), the alpha 2 polyadenylation signal (AATAAA-> AATAAG) mutation (10.2%) and the IVS-I 5' end GAGGT-GAGG->GAGG pentanucleotide (5 nt) deletion (3.3%). SS patients with coexistent alpha-thal trait did not have severe recurrent infections and none had gallstones. The high frequencies of the Saudi Arabia/India beta s haplotype and alpha-thalassemia trait contribute to the mild nature of SS disease among Kuwaiti Arabs comparable to that in eastern Saudi Arabia.

  1. The screening and morbidity pattern of sickle cell anemia in chhattisgarh. (United States)

    Panigrahi, Sumanta; Patra, P K; Khodiar, P K


    Our objective was to find out prevalence of sickle cell anemia among the population of three districts (Kanker, Dantewada and Raigarh) of Chhattisgarh with clinical and hematological profile of sickle cell disease patients. A cross sectional study was done. A total of 15,701 persons collectively from three districts voluntarily attended the mobile camp and were screened for sickle cell anemia. First solubility test were done and were confirmed by Hb electrophoresis. The prevalence of sickle cell trait (HbAS) was 1,672 (10.6 %), sickle cell disease (HbSS) and inconclusive band was 97 (0.66 %). The HbSS and inconclusive band were subjected to HPLC. Among them 12 (0.076 %) cases were double heterozygous for Hb-S and beta thalassemia minor (SB+), 2 (0.012 %) cases were double heterozygous for Hb-S and Hb-E (S/HBE), 1 (0.006 %) case was double heterozygous for Hb-S and Hb-D Punjab (S/HBD) and 22 (0.14 %) cases had Hb-S with Hb-F level more than 20 % (SSF). Maximum number of HbSS cases were 13 (2.29 %) out of 567 children in the age group 0-5 years and HbAS cases were 124 (15.6 %) out of 794 persons in the age group 21-25 years. On comparison between vaso-occlusive and steady state, homozygous patients showed decrease in Hb, HCT, MCH, RBC in vaso-occlusive crises (p < 0.001) than steady state. Also there was one moderate negative correlation in number of blood transfusion (r = 0.46) with fetal hemoglobin (HbF) level. Patients with high HbF can have severe disease. This happens due to uneven distribution of fetal hemoglobin in F-cells with mean HbF remaining constant but in our study, those who had HbF level above 15-20 % were having fewer crises.

  2. Application of Domestic Full-automatic Protein Electrophoresis System in Thalassemia Screening%国产全自动蛋白电泳系统在地中海贫血筛查中应用

    Institute of Scientific and Technical Information of China (English)



    judge the patients who whether or not suffered from thalassemia and the type of thalassemia;at the same time ,alpha and beta gene diagnosis tests had been done for all patients. Results: 181 cases alpha light-duty thalassemia, 5 cases HbH disease, 68 cases beta light-duty thalassemia,and 6 patients abnormal hemoglobin disease (including 3 HbE, 1 HbK, lHbG and 1 HbD)had been Detected and other 806 cases were phenotypic normal; but the results of genetic diagnosis showed that: 134 cases alpha light-duty thalassemia, 5 cases HbH disease, 65 cases beta light-duty thalassemia, 861 cases phenotypic normal; Comparison between screening and gene diagnosis: the diagnostic accordance rate of alpha thalassemia screening was low, only 74.03%,but HbH disease was 100% ;And the diagnostic accordance rate of beta thalassemia was higher, at 95.59%. Conclusion: The esolution of SH2020 full-automatic agarose gel electrophoresis system in the thalassemia screening is high, especially for beta thalassemia and HbH disease, but the esolution to alpha thalassemia screening is low, and there is misdiagnosis rate.

  3. Investigação genético-epidemiológica e molecular da deficiência de G-6-PD em uma comunidade brasileira G-6-PD deficiency in a Brazilian community: an investigation involving epidemiological genetics and molecular techniques

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    Mariane B. Compri


    , Spanish, and Portuguese. The Italian contribution in terms of the G-6-PD Mediterranean variant was smaller than its contribution to beta thalassemia, probably due to the Northern Italian origin of these immigrants.

  4. Mitochondrial DNA damage associated with lipid peroxidation of the mitochondrial membrane induced by Fe2+-citrate

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    Andréa M. Almeida


    Full Text Available Iron imbalance/accumulation has been implicated in oxidative injury associated with many degenerative diseases such as hereditary hemochromatosis, beta-thalassemia, and Friedreich's ataxia. Mitochondria are particularly sensitive to iron-induced oxidative stress - high loads of iron cause extensive lipid peroxidation and membrane permeabilization in isolated mitochondria. Here we detected and characterized mitochondrial DNA damage in isolated rat liver mitochondria exposed to a Fe2+-citrate complex, a small molecular weight complex. Intense DNA fragmentation was induced after the incubation of mitochondria with the iron complex. The detection of 3' phosphoglycolate ends at the mtDNA strand breaks by a 32P-postlabeling assay, suggested the involvement of hydroxyl radical in the DNA fragmentation induced by Fe2+-citrate. Increased levels of 8-oxo-7,8-dihydro-2'-deoxyguanosine also suggested that Fe2+-citrate-induced oxidative stress causes mitochondrial DNA damage. In conclusion, our results show that iron-mediated lipid peroxidation was associated with intense mtDNA damage derived from the direct attack of reactive oxygen species.Desequilíbrio/acúmulo de ferro tem sido implicado em injúria oxidativa associada a diversas doenças degenerativas tais como, hemocromatose hereditária, beta-talassemia e ataxia de Friedreich. As mitocôndrias são particularmente sensíveis a estresse oxidativo induzido por ferro - um carregamento alto de ferro em mitocôndrias isoladas pode causar uma extensiva peroxidação lipídica e a permeabilização de membrana. Nesse estudo, nós detectamos e caracterizamos danos do DNA mitocondrial em mitocôndrias isoladas de fígado de rato, expostas ao complexo Fe2+-citrato, um dos complexos de baixo peso molecular. A intensa fragmentação do DNA foi induzida após a incubação das mitocôndrias com o complexo de ferro. A detecção de finais 3' de fosfoglicolato nas quebras de fitas de DNA mitocondrial pelo ensaio 32

  5. 孕妇地中海贫血的产前筛选与诊断%Prenatal screen and diagnosis of thalassemia.

    Institute of Scientific and Technical Information of China (English)

    卢巧云; 徐婉芳


    目的 总结在我院进行产前体检者中开展地中海贫血的产前筛选与诊断结果.研究运用血红蛋白分析法进行孕妇产前筛选与诊断的意义.方法 对2 219对夫妇使用血红蛋白定量法结合基因分析,进行常规地中海贫血筛选.从中筛选出双方同为地中海贫血基因携带者的夫妇,建议其进行相关的产前诊断.对同意进行产前诊断的孕早期孕妇,采取其羊水或绒毛样本进行地中海贫血基因诊断;对同意进行产前诊断的孕中晚期孕妇,以B超下穿刺法抽取脐静脉血样进行地中海贫血基因诊断.结果 检查出夫妇一方为轻度α-地中海贫血基因携带者221例,检出率为4.98%;检查出夫妇一方为轻度β-地中海贫血基因携带者133例,检出率为3.00%.检查出双方均为地中海贫血基因携带者共13对,其中同意进行产前诊断的11例,诊断为中、重型地中海贫血胎儿5例.结论 开展孕妇地中海盆血的产前筛选与诊断,可尽早确诊中、重型地中海贫血胎儿,为家庭和社会减轻了负担与痛苦.%Objective To analyze the results of prenatal screen and diagnosis of thalassemia in 4438 pregnant women. Methods Quantitation of hemoglobin and thalassemia genetic analysis were used for screening thalassemia in 2219 couples. The couples carring thalassemia genes were suggested to take some related prenatal examinations. After permission, amniotic fluid or chorionic villi samples, and umbilical vein blood were collected from early and middle - late gestation respectively for the detection of thalassemia gene. Results Mild alpha - thalassemia gene carrier and mild beta - thalassemia gene carrier in one person of the couple were found in 221 cases ( 4.98% ) and 133 cases ( 3.00% ) respectively;thalassemia gene was found in both husband and wife in 13 couples. Of the 13 couples, 11 agreed to make prenatal diagnosis and 5 foetus of them were diagnosed as heavy thalassemia. Conclusion

  6. Triagem neonatal como um problema de saúde pública The importance of the hemoglobinopathy detection in National Neonatal Screening Programs

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    Carlos Eduardo Backes


    Full Text Available Estudos realizados na população brasileira revelam que, no Brasil, existem aproximadamente 10 milhões de indivíduos heterozigotos para os genes da Hb S, da Hb C e da talassemia beta. Embora mais de 700 hemoglobinas variantes tenham sido descritas, apenas a forma homozigótica para HbS apresenta expressão clínica mais evidente; no entanto, as formas heterozigóticas HbAS e HbSC também representam um problema de saúde pública. Em geral, os indivíduos heterozigóticos desconhecem o fato de serem portadores assintomáticos (AS, AC e, por isso, facilitam a propagação desses genes anômalos e sua interação com outras hemoglobinas variantes, talassemias, enzimopatias e esferocitoses. Como medida de prevenção e controle das hemoglobinopatias no Brasil, o Ministério da Saúde instituiu a portaria 822/01, que inclui a triagem de hemoglobinopatias no programa nacional de triagem neonatal (PNTN. O objetivo deste trabalho foi analisar a prevalência das hemoglobinopatias em crianças nascidas no período de janeiro a junho de 2003 no estado de Santa Catarina. Do total de 40.028 amostras analisadas, 399 (1% apresentaram hemoglobinopatias, e, dessas, 88,47% apresentaramm o fenótipo AS; 7,76% AC; 2,25% AD; 0,75% SS e 0,5% SC. A triagem de hemoglobinopatias é uma análise importante para a prevenção das hemoglobinopatias, as quais representam um problema de saúde pública.Studies performed in the Brazilian population show that in Brazil there are around 10 million heterozygote individuals for the Hb S and Hb C genes and beta thalassemia. Although, over 700 hemoglobin variants have been described, only homozygous states for Hb S present significant and evident clinical disorders. Furthermore, the heterozygous Hb AS and Hb SC forms have important public health aspects. In general heterozygous individuals of hemoglobin variants (AS, AC do not know that they have hemoglobin disorders because they are asymptomatic, therefore they facilitate the

  7. Prevalência de talassemias e hemoglobinas variantes em pacientes portadores de lúpus eritematoso sistêmico Prevalence of thalassemias and variant hemoglobins in patients with systemic lupus erythematosus

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    Frank S. Castro


    causes of SLE are not totally known, but It is known that environmental and genetic factors are involved. Among various clinical manifestations observed in lupus patients, anemia calls the attention because of a prevalence of 52.5% of the patients with RBC indices suggestive of anemia identified in this study. Although anemia is usually seen in patients with SLE, studies of the prevalence of hereditary anemias, particularly hemoglobinopathies, have not been carried out in populations. The objective of this work was to evaluate the prevalence of hemoglobinophaties in patients with SLE. We studied 80 blood samples of patients with SLE in Hospital das Clínicas in Goiania, Brazil. The frequency of alterations of the hemoglobin was 10.0% (8 patients. Among these alterations, the most prevalent was alpha thalassemia in 4 patients (5.0% of the studied population. The heterozygosity for hemoglobin S was seen in 2 patients (2.5%, hemoglobin C in one patient (1.25% and one patient was identified with beta thalassemia minor. No homozygous cases were found in the present study. According to this work no difference in the prevalence of hemoglobin disorders was observed between general population and patients with SLE.

  8. Analysis of thalassemia gene of 269 couples%某地区269对夫妇珠蛋白生成障碍性贫血基因检测结果

    Institute of Scientific and Technical Information of China (English)

    张艳霞; 韩泽平


    Objective The pregnant population in Guangzhou area were detected in mediterranean anemia gene to guide and standardize the premarital examination ,prenatal diagnosis ,genetic counseling ,high-risk prenatal diagno-sis and prevent the birth of children with severe thalassemia .Methods 269 couples during the period from 2013 March to September ,for examination before pregnancy and blood MCV (mean corpuscular volume) and/or hemoglo-bin electrophoresis screening positive(538 cases) were detected in mediterranean anemia gene by agarose gel electro-phoresis and gap-PCR methods .Results 269 couples accepted detection ,detection of alpha thalassemia was 28 .4% , detection of beta thalassemia rate was 19 .5% ,among them ,the couple for alpha thalassemiawith detection rate was 5 .9% ,the same as the betathalassemia detection rate was 2 .2% ,one for the alpha thalassemia ,the other party or party for beta thalassemiaalpha beta composite to poverty ,the other normaldetection rate was 4 .5% .Conclusion Mediterranean anemia examination of reproductive population ,has an important significance to eugenics and reduce the social andeconomic burden of the family .%目的:对广州地区孕前人群进行珠蛋白生成障碍性贫血基因检测,以指导规范的婚前检查、产前检查,预防重症珠蛋白生成障碍性贫血患儿的出生。方法采用琼脂糖凝胶电泳及gap-PCR方法对2013年3~9月来院进行孕前检查并且血常规平均红细胞体积(MCV)和(或)血红蛋白电泳初筛阳性的269对夫妇(共538例)进行珠蛋白生成障碍性贫血基因检测。结果接受检测的269对夫妇中,α-珠蛋白生成障碍性贫血的检出率为28.4%,β-珠蛋白生成障碍性贫血的检出率为19.5%,其中,双方夫妇同为α-珠蛋白生成障碍性贫血的检出率为5.9%,同为β-珠蛋白生成障碍性贫血的检出率为2.2%,一方为α-珠蛋白生成障碍性贫血,另一方为β-珠蛋白


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    Full Text Available Background: SEN-Virus (SEN-V-D and SEN-V-H is a DNA virus which associated with acute post transfusion hepatitis and blood transfusion is the most common mode of transmission of this virus like HCV, HBV and HIV among population. Beta thalassemia is a disease need continuous blood transfusions to manage the patient’s life; so these patients are at increased risk of infection with SEN-V. Aims of this study: This study was designed to search the prevalence of SEN-V among thalassemia patients and blood donors and to evaluate the clinical importance of SEN-Virus in thalassemia patients with or without HCV infection in Iraq and to detect the exact genomic characterization of SEN-V-D and SEN-V-H genotypes in Iraq and study of similarity of these genomes with other countries especially the neighboring countries and the homology between each isolate. Methods: One hundred and fifty eight thalassemia patients (57.6% male, 42.4% female, with mean age of 16.8±8.5 year, and one hundred and fifty healthy blood donors with randomly selected persons (58.7%male, 41.3% female, with mean age of 16.7±8.6 year; all these samples involved in this study. SEN-V and HCV had been identified by nested conventional PCR. Liver transaminases (Aspartate Transaminase and Alanine Transaminase had been determined, in addition of measure of serum ferritin levels by VIDAS. Gene sequencing and phylogenetic analysis had been studied of randomly selected amplified SEN-V D and H DNA samples. Results: SEN-V was detected in 68 from 158 (43% of thalassemia patients and 16 from 150 (10.7% of blood donors. HCV prevalence was (11.4% in thalassemia patients. There was significant increase in prevalence of SEN-V or HCV infection with age but there was no significant difference in prevalence in both with gender. SEN-V and HCV co-infection significantly increases AST level above normal range. SEN-V significantly increases ALT level above normal range and has a great significant ALT level

  10. Hepatitis C, Chronic Renal Failure, Control Is Possible!

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    Seyed-Moayed Alavian


    challenge in this regard.References1. Alavian SM, Adibi P, Zali MR. Hepatitis C Virus in Iran: Epidemiology of an Emerging Infection. Arch Iran Med. 2005; 8: 84-90.2. Alavian SM, Gholami B, Masarrat S. Hepatitis C risk factors in Iranian volunteer blood donors: a case-control study. J Gastroenterol Hepatol. 2002; 17: 1092-7.3. Alizadeh AH, Alavian SM, Jafari K, Yazdi N. Prevalence of hepatitis C virus infection and its related risk factors in drug abuser prisoners in Hamedan--Iran. World J Gastroenterol. 2005; 11: 4085-9.4. Mirmomen S, Alavian SM, Hajarizadeh B, Kafaee J, Yektaparast B, Zahedi MJ, et al. Epidemiology of hepatitis B, hepatitis C, and human immunodeficiency virus infecions in patients with beta-thalassemia in Iran: a multicenter study. Arch Iran Med. 2006; 9: 319-23.5. Alavian SM, Einollahi B, Hajarizadeh B, Bakhtiari S, Nafar M, Ahrabi S. Prevalence of hepatitis C virus infection and related risk factors among Iranian haemodialysis patients. Nephrology (Carlton. 2003; 8: 256- 60.6. Fabrizi F, Martin P, Dixit V, Bunnapradist S, Dulai G. Meta-analysis: Effect of hepatitis C virus infection on mortality in dialysis. Aliment Pharmacol Ther. 2004; 20: 1271-77.7. Einollahi B, Hajarizadeh B, Bakhtiari S, Lesanpezeshki M, Khatami MR, Nourbala MH, et al. Pretransplant hepatitis C virus infection and its effect on the post-transplant course of living renal allograft recipients. J Gastroenterol Hepatol. 2003; 18: 836-40.

  11. Frequency of β-thalassemia trait and other hemoglobinopathies in northern and western India

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    Madan Nishi


    Full Text Available Introduction : India is an ethnically diverse country with an approximate population of 1.2 billion. The frequency of beta-thalassemia trait (βTT has variously been reported from < 1% to 17% and an average of 3.3%. Most of these studies have been carried out on small population groups and some have been based on hospital-based patients. There is also a variation in the prevalence of hemoglobinopathies in different regions and population groups in the country. A high frequency of Hb D has been reported from the North in the Punjabi population, Hb E in the eastern region of India and Hb S is mainly reported from populations of tribal origin from different parts of the country. Objectives: To study the gene frequency of βTT and other hemoglobinopathies in three regions East (Kolkata, West (Mumbai and North (Delhi in larghe population group (schoolchildren for a more accurate assessment of gene frequency for planning of control programmes for haemoglobinopathies. Materials and Methods: This study included 5408 children from 11 schools in Delhi, 5682 from 75 schools in Mumbai and 957 schoolchildren from Kolkata who were screened for βTT and haemoglobinopathies. These included 5684 children from 75 schools in Mumbai and 5408 children from 11 schools in Delhi. Children were 11-18 years of age of both sexes. The final report is, however, only on 11090 schoolchildren from Mumbai and Delhi as data from Kolkata was restricted both in numbers and objectives and could not be included for comparison. Results: The overall gene frequency of βTT in Mumbai and Delhi was 4.05% being 2.68% and 5.47% in children of the two cities respectively. In Mumbai, the gene frequency was evenly distributed. Majority of the children with βTT from Mumbai were from Marathi (38.9% and Gujarati (25% speaking groups. Gene frequency was> 5% in Bhatias, Khatris, Lohanas and Schedule Castes. In Delhi, a higher incidence was observed in schoolchildren of North and West Delhi (5

  12. Avaliação dos produtos da degradação oxidativa da Hb S nos genótipos SS, SF (S/beta0 talassemia e AS, em comparação com hemoglobinas normais Evaluation of the products from oxidative damage of Hb S in SS, SF (S/beta0 thalassemia and AS genotypes compared to normal hemoglobins

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    Paulo Cesar Naoum


    talassemia.Sickle cell disease is a generic term used to determine a group of genetic alterations characterized by a dominance of Hb S. The main genotypes which compose the sickle cell disease group are as follows: SS, SF (S/beta0 thalassemia and S/Hereditary Persistence of Fetal Hemoglobin or HPFH, SFA (S/beta+ thalassemia, SC, SD and SH (S/alpha thalassemia. This study analyzes the products resulting from the oxidization of hemoglobin, identified by the methemoglobin concentration and by red blood cells with Heinz bodies, in two sickle cell genotypes (SS and S/beta0 thalassemia and in the sickle cell trait (AS compared with the normal genotype (AA. Analysis of the products resulting from hemoglobin oxidative damage, characterized by an increase in the mean levels of methemoglobin and of the number of red blood cells with Heinz bodies, which are directly related to the increase in the Hb S concentration. Thus, oxidative damage of hemoglobin diminishes among the studied genotypes in the following manner: SS>SF>AS>AA. It is important to stress that these results indicate that the simple presence of Hb S in the red blood cell, as in the AS genotype, is capable of increasing the methemoglobin concentration in 52.62% of the assessed samples and inducing the precipitation of Heinz bodies in 73.68% of cases. Elucidation of the oxidative and reductive processes of the studied hemoglobins is presented in the paper. Highlighted among the presented results is the identification, by means of alkaline agarose gel electrophoresis, of the free alpha globin fraction in all SF genotype samples originating from Hb S/beta0 thalassemia individuals. A hypothesis to explain the origin of free alpha globin, especially in the S/beta0 thalassemia genotype is proposed, as is the importance of its identification in the laboratorial diagnosis of S/beta0 thalassemia.

  13. Aspectos epidemiológicos e sociais da doença falciforme Epidemiologic and social aspects of sickle cell disease

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    Andreza Aparecida Felix


    with capillary occlusion causing acute and chronic tissue lesions in organs, which is almost always accompanied by pain. With the purpose of improving knowledge related to the epidemiologic aspects of the illness and how patients cope with it, 47 over 18-year-old patients from the city of Uberaba were studied during home visits. Of these predominantly female patients (59.6%, 78.7% were black, 17% dark-skinned and 4.3% white. In respect to the type of hemoglobinopathy, 63.8% had hemoglobin SS; 17% had hemoglobin SC and 10.6% had sickle beta-thalassemia. The majority (74.5% lived in poor regions of the city, 42.5% had concluded high school, 38.2% were either retired or did not have any specific profession, 48.9% earned up to one minimum wage and 19.1% did not receive any wages. In respect to their feelings, 38.3% showed they accepted their illness, 21.3% were resentful, 17% were sad and 46.8% said their lives had changed for the worse in relation to work and 31.9% in relation to leisure. It was possible to show with this study that SCD negatively reflects on activities related to work and on the patient's quality of life. Thus, difficulties in coping with the illness, such as poor housing, unemployment and/or badly paid jobs, may be minimized with social and psychotherapeutic accompaniment, which should be made available to every SCD patient.

  14. Hemoglobinas AS/alfa talassemia: importância diagnóstica Hemoglobins AS/alpha thalassemia: diagnostic importance

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    Renata Tomé-Alves


    , the Sickle Cell beta Thalassemia syndromes, and Hemoglobinopathies in which hemoglobin S is in association with another abnormal hemoglobin, such as hemoglobin S/C. The Sickle Cell trait (hemoglobin AS associated with Alpha Thalassemia presents alterations in the red blood cells morphology, usually absent in the heterozygous for this hemoglobin variant. The interaction between hemoglobin S and alpha Thalassemia has been described as one of the factors responsible for the improvement in the clinical picture of homozygous of hemoglobin S (Sickle Cell Anemia, decreasing the number of episodes of pain. The genetic mechanisms of this influence are evaluated using molecular analyses of the human globin genes. With the objective of verifying the presence of alpha Thalassemia in heterozygous of hemoglobin S, with anemia, sent to the Laboratory of Hemoglobins, Department of Biology, UNESP, São José do Rio Preto, SP, we analyzed 1002 blood samples with Sickle Cell trait, in the period from 1990 to 1998. The samples were picked with EDTA 5% as anticoagulant, after previous authorization of the carriers. Appropriated counseling and management requires definitive diagnosis. For the laboratorial diagnosis the blood samples were submitted to electrophoretic procedures in alkaline and acid pH and cytological evaluation of hemoglobin H. The electrophoretic procedures confirmed the presence of hemoglobin AS. The cytological evaluation evidenced the presence of alpha Thalassemia. Of this total analyzed, 16(1,59% blood samples presented the association between hemoglobin AS and alpha Thalassemia and two individuals belonged of the same family. Our results addressed us to suggest to the routine laboratories, that is important to accomplish the research of alpha Thalassemia among the Sickle Cell trait, with anemia, to verify the interaction with alpha Thalassemia, supplying to the carriers a important information on its hematological profile, genetic pattern of hemoglobinopathies and the

  15. Correlación entre niveles de ferritina sérica y unidades de transfusión recibidas por pacientes con anemias hereditarias hemolíticas en el estado de Zulia, Venezuela

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    Ana Z. Ruiz E


    / or beta thalassemia (βT. Ferritin levels are constantly monitored in these patients for early detection of iron overload. The aim study was to determine whether or not there was a correlation between serum ferritin values and the number of units of packed erythrocyte transfused in patients with SCA and βT major or intermedia for a year. A prospective study was performed with 39 patients,2 were diagnosed with SCA and 17 were diagnosed with βT. Their ages ranked between 4 to 82 years of age. These patients were treated at the “Instituto Hematológico de Occidente-Banco de Sangre Estado Zulia and Hospital Universitario de Maracaibo – Venezuela”. Serum ferritin was determined by a chemiluminescence method. The mean and standard deviation for ferritin values were 915.4 ± 567.8 ng / ml for patients with SCA and 3,338 ± 874.6 for βT (p: 0.0001. The units of packed-red blood cells transfused were 6 ± 2.3 and 21 ± 7.5, respectively (p = 0.0001. There was a statistically significant correlation between the number of packed-red blood cell units transfused and the ferritin values in the SCA group (r = 0.832, p = 0.0001, and the βT group (r = 0.491, p = 0.045. The results of this study suggest a strong correlation between serum ferritin concentrations and erythrocyte concentrate units transfused in patients with SCA but not in patients with βT.

  16. Laboratory analysis of hemolytic jaundice%溶血性黄疸患者实验室检测结果分析

    Institute of Scientific and Technical Information of China (English)

    李红萍; 李培培; 朱兆均; 朱惠君; 李娴


    results,including hematological tests,bio-chemical markers,and glucose -6 -phosphate dehydrogenase (G -6 -PD)activity.Results Patients with G -6 -PD deficiency -asso-ciated hemolytic jaundice might not have anemia.Most patients with thalassemia -associated hemolytic jaundice developed microcytic hypo-chromic anemia with mean corpuscular volume (MCV)and mean corpuscular hemoglobin (MCH)lower than normal values.Hemoglobin A2 (Hb A2 )was reduced in patients with alpha -thalassemia but increased in those with beta -thalassemia.Reticulocytes could be within or a-bove normal limits.As for urine tests,urobilirubin was negative and urobilinogen level was normal or elevated.Biochemical results showed normal direct bilirubin (DB)and mildly or moderately increased indirect bilirubin (IB)that accounted for 70% -80% of total bilirubin (TB).Alanine aminotransferase (ALT),aspartate aminotransferase (AST),and alkaline phosphatase (ALP)appeared normal.For hemo-lytic jaundice patients complicated with hepatitis virus infection,a number of indices,including ALT,AST,ALP,gamma -glutamyl transpeptidase,TB,DB and IB,showed significant elevation.Conclusion For patients with jaundice of unknown origin or not attributed to hepatitis,as well as those with mild or moderate jaundice with IB accounting for 70% -80% of TB,hemolytic diseases should be consid-ered,and G -6 -PD activity test and Hb electrophoresis screening are recommended.

  17. Selected Abstracts of the 10th International Workshop on Neonatology; Cagliari (Italy; October 22-25, 2014

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    --- Various Authors


    (Italy ABS 9. Traffiking of thymosin beta-4 in the cellular compartments of HepG2 cells at different conditions • M. Piras, M. Piludu, G. Pichiri, P. Coni, T. Cabras, R. Ambu, M. Castagnola; Cagliari and Rome (Italy ABS 10. Thyroid carcinoma in sardinian children and adolescents is often associated with autoimmune thyroiditis • P. Coni, E. Tamponi, A. Lampis, G. Pinna, A.M. Nurchi, S. Farci, M.L. Lai; Cagliari (Italy ABS 11. Prolonging nephrogenesis in preterm infants: a new approach for the prevention of renal disease in adulthood? • A. Sanna, C. Gerosa, D. Fanni, P. Van Eyken, M. Castagnola, R. Ambu; Cagliari, Rome (Italy and Leuven (Belgium ABS 12. Human adrenal gland development: morphogenesis and molecular mechanisms • E. Obinu, V. Fanos, A. Dessì, R. Ambu; Cagliari (Italy ABS 13. Biometrics application for newborns safe identification in Neonatal Intensive Care Units • A. Casanova, S. Barra, M. De Marsico, D. Riccio, L. Barberini, M. Puddu, V. Fanos; Cagliari, Rome and Naples (Italy ABS 14. Metabolomics in neonatal hypoxic-ischemic encephalopathy (HIE: a proposal for a european multicenter study • P. Gancia, G. Pomero, A. Delogu, C. Dalmazzo, G. Palmas, V. Fanos; Cuneo and Cagliari (Italy ABS 15. Longitudinal evaluation of myocardial function in infants with Hypoxic-Ischemic Encephalopathy (HIE: preliminary data • F. Vitali, S. Galletti, A. Aceti, L. Ridolfi, G. Aquilano, M. Fabi, G. Faldella; Bologna (Italy ABS 16. Changes in podocyte number during intrauterine development • M. Desogus, A. Crobe, A. Sanna, C. Gerosa, C. Fanni, C. Loddo, M. Puddu, G. Ottonello, D. Fanni; Cagliari (Italy ABS 17. Efficacy of recombinant human erythropoietin in anemic pregnant women with heterozygous beta-thalassemia • S. Angioni, V. Mais, G.B. Melis; Cagliari (Italy ABS 18. WT1 expression in ontogenesis of human fetus • R. Ambu, L. Vinci, C. Gerosa, D. Fanni, E. Obinu, A. Faa, V. Fanos; Cagliari (Italy ABS 19. Brain hypothermia in perinatal arterial ischemic

  18. Selected Lectures of the 12th International Workshop on Neonatology; Cagliari (Italy; October 19-22, 2016

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    --- Various Authors