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.
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.
Diamond-Blackfan Anemia
Stephen A. Feig, Melvin H. Freedman in Clinical Disorders and Experimental Models of Erythropoietic Failure, 2019
The long-term prognosis remains uncertain. The only group that may reach a survival plateau (Figure 5) is the steroid responders, approximately half the patients. The other half will need transfusions and chelation, bone marrow transplantation if there is a donor, and perhaps hematopoietic growth factors. The quality of life is usually good, particularly for the spontaneous remitters and the steroid responders who can be maintained on low doses. The transfusion-dependent patients can be treated, as are patients with thalassemia major. Modern chelation schemes seem to be able to dramatically postpone, if not eliminate, clinically significant transfusion-related hemosiderosis. However, the morbidity and mortality from transfusion-acquired infection is difficult to assess, and despite better selection and screening of donors, problems for these chronically transfused patients may continue. Many DBA patients are now adults, and some have had normal children, although temporary worsening of anemia was noted during pregnancy in a few. There is insufficient information to determine the current impact of bone marrow transplantation on the long-term prognosis of patients with DBA.
An Expert Overview on Therapies in Non-Transfusion-Dependent Thalassemia: Classical to Cutting Edge in Treatment
Published in Hemoglobin, 2023
Mohammadreza Saeidnia, Pooria Fazeli, Arghavan Farzi, Maryam Atefy Nezhad, Mojtaba Shabani-Borujeni, Mehran Erfani, Gholamhossein Tamaddon, Mehran Karimi
β-Thalassemia intermedia (β-TI) was first described by Rietti-Greppi Micheli in 1955 [2]. The disease features milder clinical symptoms than β-thalassemia major (β-TM). The follow-up of patients with β-TI is usually in late childhood or even adulthood. Because the patients with β-TI display mild to intermediate levels of anemia (Hb levels: 7.0–10.0 g/dL) and generally do not require regular transfusions except in specific clinical conditions, such as pregnancy, infection, and surgery, this type of thalassemia is also referred to as non-transfusion-dependent thalassemia (NTDT). Therefore, the patient’s clinical status evaluation more important for controlling the disease’s detrimental effects, better apprehending the myriad aspects of its pathophysiology, and also could be profitable for extending patients’ longevity and quality of life [1,3–6].
Prevalence of psychiatric disorders and suicidality among children and adolescents with thalassemia major—A Turkish sample
Published in Children's Health Care, 2019
Abdurrahman Cahid Örengül, İlknur Ucuz, Nergiz Oner Battaloglu, Gulcihan Ozek, Vahdet Gormez
The study was carried out in the Sanliurfa Children’s Hospital, Child Hematology clinic, where patients have access to free medical service. A total number of 270 patients in the follow-up list of the clinic with a confirmed diagnosis of TM were considered for inclusion. A total of 78 refugee children (due to language barrier and lack of interpreter), 130 underage children, and 3 children without consent forms were excluded. Therefore a total of 59 patients were included in the study. All subjects had a confirmed diagnosis of beta-thalassemia major, had regular blood transfusion in every 2–4 weeks, and used oral iron chelators (1 once in 15 days, 18 once in 3 weeks, 40 once in 4 weeks), and 18.6% of the participants had undergone splenectomy. The inclusion criteria for the patients were (a) a confirmed diagnosis of thalassemia major by a pediatric hematologist, (b) no major developmental disorder (autism spectrum disorders or mild/moderate mental retardation), and (c) consent to participate in the study.
Detection of a Rare Mutation in the Initiation Codon of the β-Globin Gene (HBB:C.2T > C; P.Met1Thr)
Published in Hemoglobin, 2023
Rawand Shamoon, Ahmed Yassin, Amir Charkaneh
An 11-year-old male proband with transfusion-dependent β-thalassemia was referred to the Genetics unit of PAR hospital lab in Erbil city for genetic testing to explore the mutations in the β-globin gene. The case was diagnosed as β-thalassemia major based on the routine clinical and hematological features as well as the Hb chromatography. The proband had typical thalassemic facies and moderate splenomegaly; he was on regular blood transfusion and iron chelation therapy. His parents’ red cell indices and chromatography were typical of the β-thalassemia trait. The proband was initially tested for 22 common β-globin gene mutations by PCR and reverse hybridization. Only one β0 mutation was detected which did not justify the proband’s clinical phenotype. The proband’s parents were therefore tested separately using the same method to double-check the results. The mother was found to carry the same mutation that was previously detected in the proband, while no mutation was detected in the father’s DNA sample. Therefore, we referred the samples of the proband and his father to a referral lab to perform Sanger sequencing for both samples. The proband as well as his parents were additionally screened for 21 common mutations/deletions in the α-globin genes using PCR and reverse hybridization.
Related Knowledge Centers
- Anemia
- Hemoglobin A
- Hemoglobinopathy
- Microcytic Anemia
- Hemoglobin
- Genetic Disorder
- Thalassemia
- Hemoglobin Subunit Beta
- Iron Overload
- Heart Failure