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Query: UMLS:C0039730 (thalassemia)
 10,305 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thalassaemia intermedia should be considered in any chronically anaemic patient presenting from the Middle East with hearing impairment. We report here three Saudi siblings with thalassaemia intermedia and features of severe bone marrow expansion, particularly invading the temporal bone. They were seen first for their otological problems before they had access to proper haematological evaluation. One member was admitted for surgical exploration of a cholesteatoma, which was then found to be marrow expansion of the temporal bone. Screening of the family revealed two more anaemic siblings with thalassaemia intermedia. Audiological examination of all the family members showed that only the two affected members had a high frequency sensori-neural hearing loss. Bone marrow expansion into the temporal bone is a rare feature of thalassaemia intermedia. Cholesteatoma-like lesion has not been previously described. It has to be considered in all cases of symptomatic thalassaemia intermedia manifesting with cavitation and lytic lesions in the mastoid system. The likelihood that sensorineural hearing loss may complicate the thalassaemias is raised and the possible mechanism for such involvement discussed. The proper management for different otological manifestations of the thalassaemias is suggested. These cases would suggest a more extensive involvement of the temporal bone in the thalassaemias than has been previously recognized. Further large scale studies are required to illuminate the subject.
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PMID:Otological manifestations of thalassaemia intermedia: evidence of temporal bone involvement and report of a unique cholesteatoma-like lesion. 161 42

Recently the molecular bases of thalassemia intermedia have been elucidated in several populations. In general this attenuated, non-transfusion dependent form of homozygous beta-thalassemia is mainly determined by a) the co-inheritance of deletion alpha-thalassemia; b) the presence of the so-called mild beta-thalassemia mutations; and more rarely, c) the inheritance of genetic conditions able to enhance the gamma-globin chain expression in adult life. Although there are several complex genetic and acquired interactions involved in the wide clinical heterogeneity of thalassemia intermedia, data in Italians indicate a definite genotype-phenotype relationship in conditions such as the co-inheritance of at least two alpha-thalassemia genes in severe and mild homozygous beta-thalassemia; the molecular homozygosity or double heterozygosity for the -87, -101 and IVS1(nt6) beta(+)-thalassemia mutations; and the coexistence of structural gamma-globin gene defects, i.e. Sicilian and Sardinian delta beta-thalassemias, deletional and non-deletional hereditary persistence of fetal hemoglobin and the polymorphism for the -158 XmnI G gamma restriction site. Thalassemia intermedia resulting from the inheritance in heterozygous beta-thalassemia of triple alpha-globin gene complex or the presence of dominant beta-thalassemia is also described and the role of these new informations in genetic counselling is discussed.
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PMID:[Current views of thalassemia intermedia]. 162 19

Thalassemia intermedia is a clinical definition applied to patients whose clinical phenotype is milder than that of thalassemia major. Criteria used to define thalassemia intermedia including age at presentation, hemoglobin or fetal hemoglobin levels and transfusion independence, are unsatisfactory. The possibility of typing the molecular defect allows a retrospective analysis of patients and offers a new tool for the diagnosis of thalassemia intermedia. Nevertheless, because of several factors that interact in the disease expression, the beta-genotype alone is not predictive of the phenotype in all cases. Although benign, the clinical course of thalassemia intermedia is characterized by several complications that can be prevented by an accurate follow-up. The conventional treatment of thalassemia intermedia remains controversial; it is hoped that recent advances in the pharmacological manipulation of hemoglobin switching will offer a therapeutic option in the future, at least to selected patients.
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PMID:Thalassemia intermedia. 775 95

Thalassaemia intermedia, defined as homozygous beta-thalassaemia in which patients are not transfusion-dependent, covers a wide range of clinical severity. It may arise because one or more genetic factors ameliorate the otherwise severe phenotype of thalassaemia major. Exactly which and how many such mutations are necessary to produce a thalassaemia intermedia phenotype is incompletely understood, although such information would be useful both clinically and for prenatal diagnosis. We examined DNA from 28 patients with thalassaemia intermedia resident in London and 28 matched patients with thalassaemia major, for 3 types of genetic modifying factors, namely; mild beta-thalassaemia mutations, the upstream XmnI G-gamma globin gene polymorphism, and alpha-globin gene deletions. The results show that the number of alleviating mutations present has a large influence on the phenotype of patients with homozygous beta-thalassaemias. A single alleviating mutation was present in 56% of thalassaemia intermedia subjects compared with 26% of thalassaemia major subjects. Two alleviating mutations were present in 33% of thalassaemia intermedia subjects compared with 1 thalassaemia major subject. No patients with thalassaemia major had 3 alleviating mutations, in contrast to 11% of those with thalassaemia intermedia. Although the findings did not account for the full range of phenotypic variation, such information is of potential value both in the clinical management and the prenatal diagnosis of homozygous beta-thalassaemia.
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PMID:Relationship between the severity of beta-thalassaemia syndromes and the number of alleviating mutations. 902 Mar 68

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.
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PMID:Molecular basis of asymptomatic beta-thalassemia major in an African American individual. 905 61

Thalassemia intermedia is a clinical entity characterized by moderate, non-transfusional anemia and hepatosplenomegaly. This phenotype can result from different genetic combinations and is sometimes present in patients with only one parent showing the thalasemia minor phenotype. We report here a family with seven members with the thalassemia beta trait, four of them with thalasemia minor and the other three with thalassemia intermedia. The genetic study of patients with thalassemia intermedia revealed the presence of the mutation IVS-1 1(G-->A) in the beta-globin gene and the heterozygous triplication of the alpha-globin gene, an uncommon association in Spain. The interaction of a mutation in the beta-globin gene with triplication of the alpha-globin gene should be considered in the diagnosis and genetic counselling in those patients with thalassemia intermedia and one normal parent.
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PMID:[Thalassemia intermedia caused by interaction of IVS-1 1(G--A) mutation in the beta-globin gene and heterozygotic triplication in the alpha-globin gene]. 958 37

Thalassemia intermedia encompasses a number of clinical conditions ranging in severity from beta-thalassemia carrier state to transfusion-dependent thalassemia major. The molecular bases of thalassemia intermedia, only partially defined, are very heterogeneous, but in general any factor able to reduce the globin-chain imbalance results in a milder form of thalassemia. These factors are the presence of a silent or mild beta-thalassemia allele, associated with a high residual beta-globin production, and the coinheritance of alpha-thalassemia or of genetic determinants that increase the gamma-chain production. Less frequent mechanisms are double heterozygosity for beta-thalassemia and triplicated alpha genes, and the presence of a hyperunstable hemoglobin variant. However, for a consistent number of beta zero-thalassemia homozygotes with a thalassemia intermedia phenotype the modifying factor has not been defined yet. In contrast, there are simple beta-thalassemia carriers who, for unknown reasons, have an unusually severe clinical phenotype.
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PMID:Relationship between genotype and phenotype. Thalassemia intermedia. 966 54

Structural hemoglobin (Hb) variants typically are based on a point mutation in a globin gene that produce a single amino acid substitution in a globin chain. Although most are of limited clinical significance, a few important subtypes have been identified with some frequency. Homozygous Hb C and Hb S (sickle cell disease) produce significant clinical manifestations, whereas Hb E and Hb D homozygotes may be mildly symptomatic. Although heterozygotes for these variants are typically asymptomatic, diagnosis may be important for genetic counseling. Thalassemia, in contrast, results from quantitative reductions in globin chain synthesis. Those with diminished beta-globin chains are termed beta-thalassemias, whereas those with decreased alpha-chain production are called alpha-thalassemias. Severity of clinical manifestations in these disorders relates to the amount of globin chain produced and the stability of residual chains present in excess. The thalassemia minor syndromes are characterized clinically by mild anemia with persistent microcytosis. Thalassemia intermedia (i.e., Hb H disease) is typified by a moderate, variably compensated hemolytic anemia that may present with clinical symptoms during a period of physiologic stress such as infection, pregnancy, or surgery. The thalassemia major syndromes produce severe, life-threatening anemia. alpha-Thalassemia major usually is incompatible with extrauterine life; beta-thalassemia major presents in infancy and requires life-long transfusion therapy and/or bone marrow transplantation for successful control of the disease. Double heterozygosity for certain structural variants and/or thalassemia syndromes may also lead to severe clinical disease. Several guidelines have been published that outline the required steps for hemoglobinopathy and thalassemia investigation. The availability of HPLC has streamlined many of these requirements, allowing an efficient stepwise diagnostic strategy for these complex disorders.
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PMID:Laboratory investigation of hemoglobinopathies and thalassemias: review and update. 1092 23

Thalassaemia intermedia is a moderate form of thalassaemia resulting from various genetic defects. We report an undescribed mechanism leading to this condition: a somatic deletion of the beta-globin gene in the haemopoietic lineage of a heterozygous beta-thalassaemic patient. We did molecular studies and haemoglobin analysis of the patient and his parents. We found that the deletion gives rise to a mosaic of cells with either one or no functional beta-globin gene and it extends to a region of frequent loss of heterozygosity called LOH11A, which is located close to the beta-globin locus. Thus, loss of heterozygosity can be a cause of non-malignant genetic disease.
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PMID:A novel mechanism for thalassaemia intermedia. 1180 58

Thalassemia intermedia patients show variable phenotypes. Hydroxyurea (HU) may benefit some of the thalassemia intermedia cases (1), however, the parameters influencing the response to HU have not been reported. In this study, the molecular parameters, alpha-globin and beta-globin genotype and the Xmn I polymorphism, were correlated with the HU response. Twenty patients with thalassemia intermedia were given HU (10-20 mg/kg) and responses were evaluated over a one year period. Twelve patients (60%) showed a good response to therapy with a significant increase in Hb and HbF levels and with elimination of the transfusion requirement in four patients. Four out of the twelve (33%) patients were positive for -alpha(3.7) deletions whereas none of the 8 non-responders were positive for alpha deletions. One each of the responders and non-responders were positive for alpha alpha alpha(anti-3.7) triplication. Three (25%) responsive and one non-responsive patients were homozygous for the IVS1-1 (G-->T) mutation. Three of the responsive patients with alpha deletions were also homozygous positive for Xmn I polymorphism. Thus, in addition to acting in synergy with the XmnI polymorphism, alpha deletions may be an independent factor predicting good response to HU in thalassemia intermedia, although this needs to be confirmation in larger studies.
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PMID:Do alpha deletions influence hydroxyurea response in thalassemia intermedia? 1601 48


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