Carrier Screening For Inherited Genetic Conditions
Vincenzo Berghella in Obstetric Evidence Based Guidelines, 2022
Beta-thalassemia is also caused by a mutation in the beta-globin gene on chromosome 11. This results in the inability to produce hemoglobin A. Individuals who are heterozygous for this mutation have beta-thalassemia minor. Depending upon the amount of normal beta-globin chain production, disease severity varies. Typically, asymptomatic mild anemia is present. Individuals who are homozygous for this mutation have beta-thalassemia major, or Cooley anemia. This disease is characterized by severe anemia with extramedullary hematopoiesis, delayed sexual development, and poor growth. Although elevated levels of Hb F are produced in an attempt to compensate for the absence of Hb A, this condition is universally fatal in late childhood unless treatment with periodic blood transfusions is initiated early. See Chap. 14 in Maternal-Fetal Medicine Evidence Based Guidelines.
Hemoglobinopathies and Thalassemias
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
In an older terminology the term thalassemia major referred to a severe disease with hemoglobin concentrations <6 g/dL; this is now known to be due to homozygosity for one of many different thalassemia genes. Thalassemia minor denotes the heterozygous state characterized by a mild microcytosis. In thalassemia intermedia, as the name implies, hemoglobin concentration ranges between 7 and 10 g/dL; it is most often the compound heterozygous state for either a structural variant and a thalassemia allele or for two different thalassemia genes. Rare cases with only subtle erythrocyte morphologic abnormalities but who are parents of a child with thalassemia major have been referred to as thalassemia minima, or silent carriers. Understanding the organization of the genes governing the synthesis of hemoglobin allows a genetic classification that connotes depression in the amount of specific globin chains present in cells.
Ethical implications and practical considerations of ethnically targeted screening for genetic disorders: the case of hemoglobinopathy screening
Simon M. Dyson, Karl Atkin in Genetics and Global Public Health, 2014
The evolutionary push/pull of Hb genes has resulted in an uneven distribution of hemoglobinopathy-causing variants in racial/ethnic groups with genetic ancestry from regions of the world with endemic malaria. For example, alpha-thalassemias occur most commonly in people from China and Southeast Asia, while beta-thalassemia mutations are most common in selected Eastern Mediterranean populations, followed by Asian and African populations. The Hb S mutation, which is the cause of SCD, is associated with several variants that mostly originated in Western and Central Africa as well as one variant that is associated with the Middle East and India and mostly milder disease manifestations (Crawford et al. 2002). The Hb C mutation is associated with West Africa and the Hb D mutation with parts of India and Pakistan. Furthermore, these variants have been spread around the world by migration and population admixture resulting in widespread occurrence globally (World Health Organization 2010). In the United States, birth prevalences of SCD in California are reported to be 1 per 396 births in Black populations, 1 per 36,497 Hispanic births and 1 per 122,988 White non-Hispanic births (Lorey et al. 1996).
Homeobox A5 and A9 expression and beta-thalassemia
Published in British Journal of Biomedical Science, 2021
EAE Badr, IE-T El-Sayed, MKR Alasadi
β-thalassemia is a spectrum of hereditary blood disorders characterized by defects in the synthesis of the β chains of haemoglobin resulting in a range of phenotypes from severe anaemia to clinically asymptomatic individuals [1,2]. The severity of symptoms is related to the extent of absent production of β-globin chain. The genotypic variability of β-globin synthesis is designated as β(+) for decreased production and β(0) for absent production. The phenotypic variability is designated as either minor, intermediate, or major. β-thalassemia minor is heterozygosity with one unaffected beta-globin gene and one affected, either β(+) or β(0). Homozygosity or compound heterozygosity with β(+) or β(0) causes intermediate and major. These are distinguished clinically by the severity of anaemia and not by genotype [3]. The molecular defects in β-thalassemia result in absent or reduced β-chain production. Alpha chain synthesis is unaffected, and hence there is an imbalanced globin chain production leading to an excess of α chains. In the absence of their partners, they are unstable, and they precipitate in the red cell precursors, giving a rise to large intracellular inclusions, which interferes with red cell maturation [4]. Hence, the pathogenesis of β-thalassemia has been attributed to ineffective erythropoiesis due to intramedullary apoptosis and delayed maturation of erythroid progenitor cells [5].
Crosstalk between cytokine profile, redox, and iron status in β-Thalassemia: relation to frequency/duration of blood transfusion
Published in Pediatric Hematology and Oncology, 2019
Walaa Arafa Keshk, Nahed Mohammed Hablas, Noha El Sayed Esheba, Shereen Awny Abd Elsalam
β-Thalassemia, an autosomal recessive blood disease, is a significant public health problem and is the most common genetically determined chronic hemolytic anemia in Egypt. β-Thalassemia occurs as a result of β-globin genes or their regulatory regions' mutations with resulting imbalance in α/β-globin chain synthesis, incompetent erythropoiesis, decreased red blood cell survival and anemia [1]. Depending on the disease clinical severity, β-thalassemia is classified into minor, intermedia, and major. β-Thalassemia minor is characterized by mild anemia with no need for regular blood transfusion. On contrary, β-thalassemia major is characterized by severe anemia and requires frequent blood transfusions for red blood cells restitution but β-thalassemia intermedia represented with clinical severity which lies between that of β-thalassemia major and β-thalassemia minor [2, 3].
Epidemiologic study of major complications in adolescent and adult patients with thalassemia in Northeastern Thailand: the E-SAAN study phase I
Published in Hematology, 2018
Nattiya Teawtrakul, Arunee Jetsrisuparb, Saranya Pongudom, Chittima Sirijerachai, Kanchana Chansung, Chinadol Wanitpongpun, Supan Fucharoen
Thalassemia syndrome is the most common autosomal recessive disorder worldwide. The disease is caused by a defect in globin genes synthesis resulting in the abnormality of amount and quality of the globin chain production. The clinical manifestations of thalassemia can be classified into three different phenotypes according to the severity of the disease that include: (1) transfusion-dependent thalassemia (TDT), (2) non-transfusion-dependent thalassemia (NTDT) and (3) thalassemia minor. TDT includes patients with severe forms of thalassemia, e.g. homozygous β0 thalassemia or hemoglobin E/β-thalassemia who have severe clinical symptoms and require regular red blood cell transfusions for survival. NTDT includes patients with moderate forms of thalassemia, e.g. hemoglobin H disease and some cases of hemoglobin E/β-thalassemia who have moderate anemia, moderate splenomegaly and require occasional red blood cell transfusions [1,2]. Thalassemia minor includes patients who have no clinical symptoms and do not require transfusions.
Related Knowledge Centers
- Anemia
- Hemoglobin A
- Hemoglobinopathy
- Microcytic Anemia
- Hemoglobin
- Heart Failure
- Genetic Disorder
- Thalassemia
- Hemoglobin Subunit Beta
- Iron Overload