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Thalassemia Intermedia (thalassemia + intermedia)
Selected AbstractsEvaluation of the genetic basis of phenotypic heterogeneity in north Indian patients with Thalassemia majorEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 6 2010Nidhi Sharma Abstract Objectives: To assess the molecular basis of phenotypic heterogeneity in north Indian patients with thalassemia major (TM). Methods: To determine the clinical severity, 130 patients of TM were studied for the age of first presentation and frequency of blood transfusion. The type of beta mutations, Xmn,1G, polymorphism and G6PD Mediterranean mutation was characterized. Analysis of the phenotypic presentation and the genotype was performed. Results: Majority (83.8%) presented before 1 year of age (mean 8.8 months). The caste distribution showed 41.6% were Aroras and 32.3% were migrants from Pakistan. IVS1-5(G,C) was commonest (32.7%) and the common five Indian mutations comprised of 88.4% of alleles. The mean age of presentation with IVS1-5(G,C), Fr 8/9, (+G) 619-bp del and IVS1-1(G,T) homozygosity was 4.3, 6, 3.4 and 9.1 months respectively. Xmn,1G, status showed ,/, in 66.9%, +/, in 26.1% and +/+ in 6.9% patients. Xmn,1G,,/, presented before 1 year of age. The mean age of presentation with +/+ was 18.3 months. Six hemizygous boys and one heterozygous girl with G6PD Mediterranean were found (prevalence 5.3%). Eight patients could be reclassified as thalassemia intermedia on follow up. Conclusions: This study showed that majority of TM in north India present before 1 year of age and homozygous 619-bp deletion presents the earliest. The presence of Xmn-1G, polymorphism delays the presentation, is associated with the IVS 1-1 (G,T) and shows variable improvement with hydroxyurea therapy. Based on the results of genotyping, reevaluation of patients can improve the outcome in a few patients. [source] Distribution and frequency of , -thalassemia mutations in northwestern and central GreeceEUROPEAN JOURNAL OF HAEMATOLOGY, Issue 2 2003I. Georgiou Abstract: Objectives : , -Thalassemia is a common autosomal recessive disorder resulting from over 200 different mutations of the , -globin genes. The spectrum of , -thalassemia mutations in Greece has been previously described in the population of the capital city of Athens, or in , -thalassemia patients having transfusion therapy. The aim of the present study was to identify the distribution of the most common , -thalassemia mutations in the population of northwestern and central Greece. Methods : The data for this study were derived from a total of 1130 unrelated subjects including 46 , -thalassemia major, three , -thalassemia intermedia and 1081 carriers identified in our antenatal screening program. , -Thalassemia mutations were identified by ARMS, DGGE and Reverse Dot Blot. Results : The most common mutation, IVS-I-110, is followed, in order of frequency, by the mutations Cd-39, IVS-I-1, IVS-II-1, Cd-6, IVS-I-6, IVS-I-5, IVS-II-745, Cd-5 and 44 bp del. IVS-I-110 and Cd-39 frequencies are similar with those found in other Balkan countries. Significant differences in regional distribution were observed. The results showed a clear drift of the distribution of the most frequent IVS-I-110 mutation in the south,north (29.4, 40.0, 44.6 and 61.7%) and the east,west axis (31.8 and 44.6%). Conclusions : Population screening and prenatal diagnosis are significantly facilitated by these data. Furthermore, the detailed distribution tables of , -thalassemia mutations are essential for counseling and extraction of genetic diversity estimates for population genetic studies in other inherited disorders. [source] Thalassemia: macroscopic and radiological study of a caseINTERNATIONAL JOURNAL OF OSTEOARCHAEOLOGY, Issue 3 2007A. Lagia Abstract Differentiation of the genetic and the acquired anaemias, particularly in areas of the world where they may co-exist, has been a challenge for palaeopathologists for over 100 years. In this paper we present macroscopic and radiographic skeletal lesions that are associated with the thalassemias in a 14-year-old girl from a modern reference collection of the University of Athens. This individual is of known sex, age, cause of death, place and dates of birth and death. The case is examined in terms of epidemiology, growth, distribution and severity of lesions and differential diagnosis. The entire skeleton is affected by marrow hyperplasia: lesions of the axial skeleton are extreme, and the appendicular skeleton is severely affected as well. The odontofacial manifestations that are diagnostic of thalassemia and differentiate it from other anaemias are present and include: maxillary and mandibular hyperplasia, reduced sinuses, displacement of maxillary dental structures, overbite, and generalised osteopenia. The development of extreme bone lesions and the ,advanced' age-at-death of this individual is explained as either the result of thalassemia major under a low transfusion regimen that was the norm during her lifetime, or to a form of thalassemia intermedia that allows survival to later life at the expense of gross skeletal alterations. The present status of skeletal studies in Greece does not support the identification of a genetic anaemia in past populations. The potential contribution of the current analysis in differentiating the anaemias in antiquity is evaluated. Copyright © 2006 John Wiley & Sons, Ltd. [source] Red cells playing as activated platelets in thalassemia intermediaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2010P. M. MANNUCCI See also Taher AT, Musallam KM, Karimi M, El-Beshlawy A, Belhoul K, Daar S, Saned M, Cesaretti C, Cappellini MD. Splenectomy and thrombosis: the case of thalassemia intermedia. This issue, pp 2152,8. [source] Splenectomy and thrombosis: the case of thalassemia intermediaJOURNAL OF THROMBOSIS AND HAEMOSTASIS, Issue 10 2010A. T. TAHER See also Mannucci PM. Red cells playing as activated platelets in thalassemia intermedia. This issue, pp 2149,51. Summary.,Background:,Hypercoagulability in splenectomized patients with thalassemia intermedia (TI) has been extensively evaluated. However, clinical and laboratory characteristics of patients who eventually develop overt thromboembolic events (TEE) are poorly studied. Patients/Methods:,Three Groups of TI patients (n = 73 each) were retrospectively identified from a registry involving six centers across the Middle East and Italy: Group I, all splenectomized patients with a documented TEE; Group II, age- and sex-matched splenectomized patients without TEE; and Group III, age- and sex-matched non-splenectomized patients without TEE. Retrieved data included demographics, laboratory parameters, clinical complications, and received treatments that may influence TEE development, and reflected the period prior to TEE occurrence in Group I. Results:,The mean age of Group I patients at development of TEE was 33.1 ± 11.7 years, with a male to female ratio of 33:40. TEE were predominantly venous (95%) while four patients (5%) had documented stroke. Among studied parameters, Group I patients were more likely to have a nucleated red blood cell (NRBC) count , 300 × 106 L,1, a platelet count , 500 × 109 L,1 and evidence of pulmonary hypertension (PHT), or be transfusion naïve. The median time to thrombosis following splenectomy was 8 years. Patients with an NRBC count , 300 × 106 L,1, a platelet count , 500 × 109 L,1, or who were transfusion naive also had a shorter time to thrombosis following splenectomy. Conclusion:,Splenectomized TI patients who will develop TEE may be identified early on by high NRBC and platelet counts, evidence of PHT, and transfusion naivety. [source] Magnetic resonance evaluation of hepatic and myocardial iron deposition in transfusion-independent thalassemia intermedia compared to regularly transfused thalassemia major patients,AMERICAN JOURNAL OF HEMATOLOGY, Issue 4 2010Ali T. Taher No abstract is available for this article. [source] Serum ferritin underestimates liver iron concentration in transfusion independent thalassemia patients as compared to regularly transfused thalassemia and sickle cell patientsPEDIATRIC BLOOD & CANCER, Issue 3 2007Zahra Pakbaz MD Abstract Serum ferritin (SF) and liver iron concentration (LIC), as measured by SQUID biosusceptometry, were assessed in a convenience sample of transfusion independent thalassemia patients (nTx-Thal, n,=,26), regularly transfused thalassemia (Tx-Thal, n,=,89), or sickle cell patients (SCD, n,=,45) to investigate the severity of iron overload and the relationship between SF and LIC in nTx-Thal compared to SCD and Tx-Thal. SF correlated with LIC (RS,=,0.53, P,<,0.001), but was found to be a poor predictor for LIC. SF was significantly lower (P,<,0.001) in nTx-Thal patients than in other groups, despite similar LIC values. The SF-to-LIC ratio was significantly lower in nTx-Thal compared to Tx-Thal and SCD patients (median of 0.32, 0.87, and 1.2, respectively: P,<,0.001). Due to underestimation of LIC by ferritin levels, chelation treatment may be delayed or misdirected in patients with thalassemia intermedia. Pediatr Blood Cancer 2007;49:329,332. © 2007 Wiley-Liss, Inc. [source] Urinary hepcidin in congenital chronic anemiasPEDIATRIC BLOOD & CANCER, Issue 1 2007Susan L. Kearney MD Abstract Background Hepcidin, a regulator for iron homeostasis, is induced by inflammation and iron burden and suppressed by anemia and hypoxia. This study was conducted to determine the hepcidin levels in patients with congenital chronic anemias. Procedure Forty-nine subjects with anemia, varying degrees of erythropoiesis and iron burden were recruited. Eight children with immune thrombocytopenia were included as approximate age-matched controls. Routine hematologic labs and urinary hepcidin (uhepcidin) levels were assessed. For thalassemia major (TM) patients, uhepcidin was obtained pre- and post-transfusion. Results In TM, uhepcidin levels increased significantly after transfusion, demonstrated wide variance, and the median did not significantly differ from controls or thalassemia intermedia (TI). In both thalassemia syndromes, the hepcidin to ferritin ratio, a marker of the appropriateness of hepcidin expression relative to the degree of iron burden, was low compared to controls. In TI and sickle cell anemia (SCA), median uhepcidin was low compared to controls, P,=,0.013 and <0.001, respectively. In thalassemia subjects, uhepcidin levels were positively associated with ferritin. In subjects with SCA, uhepcidin demonstrated a negative correlation with reticulocyte count. Conclusions This study examines hepcidin levels in congenital anemias. In SCA, hepcidin was suppressed and inversely associated with erythropoietic drive. In thalassemic syndromes, hepcidin was suppressed relative to the degree of iron burden. Transfusion led to increased uhepcidin. In thalassemia, the relative influence of known hepcidin modifiers was more difficult to assess. In thalassemic syndromes where iron overload and anemia have opposing effects, the increased erythropoietic drive may positively influence hepcidin production. Pediatr Blood Cancer 2007;48:57,63. © 2005 Wiley-Liss, Inc. [source] Increased ,-globin gene expression in ,-thalassemia intermedia patients correlates with a mutation in 3,HS1AMERICAN JOURNAL OF HEMATOLOGY, Issue 11 2007Adamantia Papachatzopoulou We report a novel set of genetic markers in the DNaseI hypersensitive sites comprising the human ,-globin locus chromatin hub (CH), namely HS-111 and 3,HS1. The HS-111 (,21 G>A) and 3,HS1 (+179 C>T) transitions form CH haplotypes, which occur at different frequencies in ,-thalassemia intermedia and major patients and normal (nonthalassemic) individuals. We also show that the 3,HS1 (+179 C>T) variation results in a GATA-1 binding site and correlates with increased fetal hemoglobin production in ,-thalassemia intermedia patients. In contrast, the HS-111 (+126 G>A) transition, found in three normal chromosomes, is simply a rare polymorphism. We conclude that the CH haplotypes are useful genetic determinants for ,-thalassemia major and intermedia patients, while the 3,HS1 (+179 C>T) mutation may have functional consequences in ,-globin genes expression. Am. J. Hematol., 2007. © 2007 Wiley-Liss, Inc. [source] Hb Florida: A novel elongated C-terminal ,-globin variant causing dominant ,-thalassemia phenotypeAMERICAN JOURNAL OF HEMATOLOGY, Issue 5 2006B.I. Weinstein Abstract We report here a new frameshift mutation in exon 3 of the ,-globin gene, a single nucleotide deletion (-C) in between codons 140/141 (GCC/CTG,GCC/TG), found in an 8-year-old Argentinean girl with clinical picture of thalassemia intermedia. It leads to a ,-chain that is elongated to 156 amino acids [(141)Trp-Pro-Thr-Ser-Ile-Thr-Lys-Leu-Ala-Phe-Leu-Leu-Ser-Asn-Phe-(156)Tyr-COOH]. The resulting hemoglobin, which we named Hb Florida, was not detected in peripheral blood; however, erythroid hyperplasia and dyserythropoiesis with large inclusion bodies on methyl violet staining were observed in bone marrow, suggesting that this is a hyperunstable variant producing a dominant ,-thalassemia phenotype, since the other ,-allele was completely normal. Am. J. Hematol. 81:358,360, 2006. © 2006 Wiley-Liss, Inc. [source] | ||||||||||