Editorials and Perspectives Beta-thalassemia: from genotype to phenotype (original) (raw)
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Phenotypic Prediction in beta-Thalassemia
Annals of the New York Academy of Sciences, 1998
O ver 150 mutations 1 affecting the β-globin gene lead to a reduction (β+) or absence (β 0) of β-globin production, resulting in the three main clinical phenotypes of β-thalassemia: thalassemia major (TM), thalassemia trait (TT), and thalassemia intermedia (TI). 2 Despite the ability to accurately define the β-thalassemia mutations, identification of the patients with TI and prediction of their clinical severity, remain a problem in genetic counselling and prenatal diagnosis because the disease is influenced not only by the type of β-thalassemia mutations, but also by other factors such as those affecting the αand γ-globin gene expression. 3 We have examined 87 patients with a spectrum of clinical phenotypes within the syndrome of TI with two main objectives: (1) to determine if it is possible to consistently predict phenotypic severity from the known genotypic factors and (2) to identify the factors that affect the genotype-phenotype relationship and to assess their relative importance. MATERIALS AND METHODS Eighty-seven patients (representing 74 families) were referred to the MRC Molecular Haematology Unit from the United Kingdom and abroad for clarification of diagnosis and further management. The families were drawn from the following ethnic backgrounds: Asian Indian (35.1%); Middle Eastern (24.3%); Mediterranean (21.6%); Northern European (14.9%); and Southeast Asian/Chinese (4.1%) (TABLE 1). There was more than one patient in 12 families; two siblings in eight families, parent and child in three families, and three siblings in one family. Whenever possible, all family members, with and without thalassemia were examined in parallel with the probands. Criteria for inclusion as TI follow the broad clinical guidelines, i.e., a disorder that is milder than TM but more severe than asymptomatic TT. Patients were classified as mildly affected if they maintained a Hb level of ≥ 7.5 gm/dl without blood transfusion, or need blood transfusions at a frequency of less than once every two years, or less than twice a year if transfusion was started after age 10. They are considered severe if transfusion requirements begin at age 4 or above with a frequency between 6 weeks and four months, or between three and four months if transfusion requirements commenced before age 4 years. Those who fall between the two groups are classified as moderate.
Beta Thalassemia [Working Title], 2020
Beta-thalassemia is a genetic disease caused by mutations in the β-globin gene, resulting in partial or complete deficiency of β-chain. Deficiency of β-chain was accompanied by excess unmatched α-globin chains with subsequent dyserythropoiesis, oxidative stress, and chronic anemia. The main therapeutic option is blood transfusion that improves the anemic status but unfortunately exacerbates iron overload status. Till now, the only curative measure is allo-hematopoietic stem cell transplantation. New diagnostic and therapeutic modalities are now available. These include the preimplantation genetic diagnosis and new tools in the assessment of iron overload. Also, new therapeutic options aimed at different targets are being developed; for example, therapies that stimulate the synthesis of γ-globin and reduce the synthesis of α-globin, as well as the iron excess, dyserythropoiesis, and oxidative stress. However, the most likely ideal approach is efficient prevention, through genetic counseling, carrier detection, and prenatal diagnosis.
Revisiting beta thalassemia intermedia: past, present, and future prospects
Hematology (Amsterdam, Netherlands), 2017
The spectrum of thalassemias is wide ranging from thalassemia minor, which consists of mild hypochromic microcytic anemia without obvious clinical manifestations, to thalassemia major (TM), which is characterized by severe anemia since the first years of life and is transfusion dependent. Thalassemia intermedia (TI) describes those patients with mild or moderate anemia. To describe the genetic features and major clinical complications of TI, and the therapeutic approaches available in the management of this disease. Publications from potentially relevant journals were searched on Medline. Over the past decade, the understanding of TI has increased with regard to pathophysiology and molecular studies. It is now clear that clinical presentation and specific complications make TI different from TM. It is associated with greater morbidity, a wider spectrum of organ dysfunction and more complications than previously thought. TI is not a mild disease. The interplay of three hallmark patho...
Update on Thalassemia: Clinical Care and Complications
Hematology/Oncology Clinics of North America, 2010
b-Thalassemia, originally named Cooley anemia, initially was described by Dr Cooley in 1925 in Detroit as an inherited blood disease. 1 It is speculated that thalassemia was first recognized in the United States and not in its area of highest prevalence (the Mediterranean) because its presentation as a distinct clinical entity was masked by the fact that malaria, with its similar clinical picture of hemolysis, anemia, and splenomegaly, was ubiquitous in that region. 1 Thus, patients who had this clinical triad were assumed to have malaria, not thalassemia. 1 Now it is recognized that various types of thalassemia are inherited anemias caused by mutations at the globin gene loci on chromosomes 16 and 11, affecting the production of a-or b-globin protein, respectively. 2,3 The thalassemia syndromes are named according to the globin chain affected or the abnormal hemoglobin produced. Thus, b-globin gene mutations give rise to b-thalassemia and a-globin mutations cause a-thalassemia. In addition, the thalassemias are characterized by their clinical severity (phenotype). Thalassemia major (TM) refers to disease requiring more than eight red blood cell (RBC) transfusions per year and thalassemia intermedia (TI) to disease that requires no or infrequent transfusions. 4 Thalassemia trait refers to carriers of mutations; such individuals have microcytosis and hypochromia but no or only mild anemia. 5,6 Untreated TM uniformly is fatal in the first few years of life. 1 In addition, TM and severe TI can lead to considerable morbidity affecting nearly all organ systems. 7-9 The combination of early diagnosis, improvements in monitoring for organ complications, and advances in supportive care, however, have enabled many patients who have severe thalassemia syndromes to live productive, active lives well into adulthood. 9-11 EPIDEMIOLOGY Similar to sickle cell disease and G6PD deficiency, the high prevalence of a-and b-thalassemia genotypes is believed a consequence of an evolutionary protection of
β -Thalassemia: A Current Overview
International Journal of Health Sciences and Research, 2016
Beta-thalassemia is a group of hereditary blood disorders characterized by reduced or absent beta globin chain synthesis, resulting in chronic hemolytic anemia and ineffective erythropoiesis. Individuals with β-thalassemia have widely variable clinical manifestations, extending from nearly asymptomatic to severe anemia requiring lifelong regular blood transfusions and complicated by multiple organ damage. Chronic transfusion inevitably leads to iron overload which necessitates iron chelation therapy. Current overview about the disease clinical picture, method of diagnosis, complications and principles of management is going to be discussed in brief.