Introduction
Kate Reed in Gender and Genetics, 2012
Within the UK, in the first and second trimester of pregnancy women are offered a range of blood tests which include screening for maternal health and diseases (e.g. blood type, sexually transmitted diseases), and screening for fetal health. The latter tests include haemoglobinopathy screening for the sickle cell or thalassaemia trait. Sickle cell disorders (SCDs) and thalassaemia major are recessive conditions where individuals who inherit a deleterious gene from both parents develop the disease (Atkin, Ahmad and Anionwu 1998). These disorders are serious conditions. They affect the haemoglobin, a part of the blood that carries oxygen around the body. People who have these conditions will need specialist care throughout their lives (NHS Antenatal and Newborn Screening Programmes 2010).
The Genetic Risk of a Couple Aiming to Conceive
Carlos Simón, Carmen Rubio in Handbook of Genetic Diagnostic Technologies in Reproductive Medicine, 2022
The other carrier-screening program offered initially involved hemoglobinopathies (25). Sickle-cell disease is prevalent among individuals of African or African-American origin, 1 in 12 being heterozygotes for sickle-cell anemia (i.e., having the phenotype known as sickle-cell trait). Most affected individuals of African or African-American descent are the result of a missense mutation on codon 6 of the β-globin gene of hemoglobin, a single pathogenic variant resulting in a substitution of valine to glutamic acid in β-globin. A minority of cases from the Middle East have other hemoglobinopathy mutations. Irrespective of ethnic origin, heterozygosity can be identified through hemoglobin electrophoresis, assessing the motility of the protein gene product. Hemoglobin electrophoresis is also utilized for screening for carriers of β-thalassemias, hemoglobinopathies which are more frequent among Greeks, Italians (particularly Sicilians), Turks, Arabs, southern Iranians, and Asian Indians. Carrier detection is based on the presence of anemia which is not due to iron deficiency. The phenotype is further characterized by a mean corpuscular volume of less than 80 fL (microcytosis) and normal iron saturation levels. Hemoglobin electrophoresis shows decreased hemoglobin β but increased hemoglobin F as a characteristic for detecting β-thalassemia (26). DNA-based methods are now standard.
Anemia: Approach to Diagnosis
Harold R. Schumacher, William A. Rock, Sanford A. Stass in Handbook of Hematologic Pathology, 2019
The patient with normocytic anemia who has no evidence of acute blood loss but has an elevated reticulocyte index is probably hemolyzing. Etiologies of hemolytic anemia include hereditary membrane defects, red cell enzyme defects, hemoglobinopathies, acquired membrane abnormalities, splenomegaly, immune-mediated hemolysis, mechanical red cell trauma, toxic effects, drug effects, and infectious agents. Infants and children with hemolysis will usually be found to have an inherited hemoglobinopathy, enzymopathy, or immune-mediated hemolysis. Laboratory and clinical features similar to those found in adults lead to accurate diagnosis. An initial step in the laboratory evaluation is review of the peripheral smear in search of schistocytes, helmet cells, or fragmented red cells, which are highly specific for intravascular hemolysis.
Distribution characteristics and clinical phenotype analyses of hemoglobin variants in the Z region of Central Guangxi, Southern China
Published in Hematology, 2023
Lizhu Chen, Ning Tang, Jun Huang, Xiaobao Wei, Qingyan Zhong, Tizhen Yan, Shiqiang Luo
Hemoglobinopathy is a kind of hereditary blood disease caused by an abnormal structure or insufficient synthesis of the globin chain. Studies have shown that when the structure of the peptide chain changes, unstable hemoglobin variants can be generated, leading to gene mutation transcription or post-transcription metabolic abnormalities, and the expression of the affected globin chain will decreases, resulting in thalassemia manifestations [13]. In this study, 174 cases of group J, K, Q, G and E hemoglobin variants were found by hemoglobin electrophoresis in Guizhong, Southern China, and the prevalence of hemoglobinopathy was 0.73% (174/23709), higher than that of Meizhou, Guangdong Province (0.477%) [14], Shaokwan, Guangdong Province (0.46%) [15] and Fujian Province (0.26%) [16]. We identified 71 cases of mutations in the Z zone, including 24 cases of α-globin chain hemoglobin variants (Hb Cibeles, Hb J-Broussais, Hb G-Honolulu, Hb J-Wenchang-Wuming, Hb Ube-2, Hb Handsworth, Hb Q-Thailand), and 47 cases of β-globin chain hemoglobin variants (Hb G-Siriraj, Hb NewYork, Hb Anti-Lepore Liuzhou).
Overview of current progress and challenges in diagnosis, and management of pediatric sickle cell disease in Democratic Republic of the Congo
Published in Hematology, 2022
Emmanuel Tebandite Kasai, Jean Pierre Alworong’a Opara, Justin Ntokamunda Kadima, Masendu Kalenga, Salomon Batina Agasa, Roland Marini Djang’eing‘a, François Boemer
Hemoglobinopathy is defined as a blood pathology caused by genetic mutations that lead to qualitative and quantitative changes in structure and quantity of hemoglobin (Hb) chains [1]. To date, over a thousand variants of hemoglobin are described in the HbVar database. Not all these variants are clinically significant [2]. Globally, hemoglobinopathies fall into two main groups, including structural variants of hemoglobin (abnormal hemoglobins) and thalassemia syndromes (α-and β-thalassemia). Hemoglobin is a tetramer made up of two chains of α-globin and two chains of β-globin working together with heme to transport oxygen in the blood [1]. Normal adult hemoglobin (HbA) is referred to as αA2βA2 [1]. Variant hemoglobin is derived from genetic mutations in the structural genes of α-globin (HBA1 or HBA2) or β-globin (HBB) (exons).
Thalassemia in Asia 2021 Thalassemia in Brunei Darussalam
Published in Hemoglobin, 2022
Seow-Chin Chong, Sofian Metassan, Noorainun Yusof, Roserahayu Idros, Norehan Johari, Ihsan N. Zulkipli, Hazim Ghani, Mei-Ann Lim, Surita Taib, Zen-Huat Lu, Mas R.W. Abdul-Hamid
Hemoglobinopathies are a diverse group of inherited blood disorders characterized by decreased expression of the functional hemoglobin (Hb) proteins. The disorder results from hereditary mutations that cause qualitative defects leading to structurally abnormal Hb variants such as Hb S (HBB: c.20A>T), Hb E (HBB: c.79G>A) and Hb Constant Spring (Hb CS or HBA2: 427 T>C) or quantitative defects of the globin expression as in thalassemia disorders. Thalassemia is the most common type of hemoglobinopathy. Additionally, there are also cases where Hb variants can be associated with thalassemia genotypes and may cause clinical complications [1]. The thalassemia types vary depending on which polypeptide chains’ expressions are affected. The globin chains are coded by the α gene clusters (HBA1/HBA2) on chromosome 16 and the β-globin gene cluster (HBB) on chromosome 11 [2]. Decreased globin chain expressions can be caused by deletion of structural genes, or mutations that cause decreased RNA or protein synthesis or stability [3]. Where there is an imbalance of α and β chains, there is a formation of unstable tetramers and an accumulation and precipitation of unpaired chains that is followed by hemolysis, and ineffective erythropoiesis [4]. Most thalassemia cases are inherited in an autosomal recessive manner, and thus, family history is effectively part of the primary line of establishing a diagnosis.
Related Knowledge Centers
- Hemoglobin C
- Hemoglobin Variants
- Red Blood Cell
- Hematologic Disease
- Dominance
- Thalassemia
- Sickle Cell Disease
- Hemoglobin E
- Alpha-Thalassemia
- Beta Thalassemia