Understanding the key features of sickle cell disease and beta thalassaemia
Sickle cell disease (SCD) and beta thalassaemia belong to a group of inherited conditions known as haemoglobinopathies, where the haemoglobin in red blood cells (RBCs) is affected by a genetic alteration in the globin genes. This results in an abnormal structure or reduced production of haemoglobin, which can cause chronic anaemia and other serious health problems. Each year, around 245 babies are diagnosed with a clinically significant haemoglobinopathy through the newborn screening programme in England (NHS England, 2022).
SCD and beta thalassaemia are the two most common haemoglobinopathies (Pecker et al, 2019); they are also among the most common inherited conditions in the UK (National Institute for Health and Care Excellence 2025). In May this year, there were an estimated 17,653 people with SCD and 2,561 with clinically significant beta thalassaemia on the National Haemoglobinopathy Register (2025). However, as not all individuals are registered, the real number is likely to be higher, with efforts ongoing to establish a database for more accurate reporting.
SCD and beta thalassaemia are life-long conditions. SCD causes RBCs to become sickle-shaped, while beta-thalassemia leads to reduced production of normal haemoglobin. While both diseases can lead to chronic anaemia, they are multi-systemic and, in the case of SCD, complications can happen quickly and unexpectedly (Hackett, 2021).
The age that people present with clinical symptoms depends on many factors, including the type of genetic alteration inherited, environment, access to preventive care and prompt management of acute symptoms and illness.
The multi-systemic nature of SCD and beta thalassaemia, and the fact that they are relatively common inherited blood disorders, means all nurses and midwives should be aware of these conditions and how to provide effective care and support to affected individuals and their families. However, evidence suggests that there can be deficits in practitioners’ knowledge, skills and attitudes in caring for individuals with these conditions and that in the case of SCD, these have contributed to avoidable complications, morbidity and mortality (Sickle Cell Society 2023; All-Party Parliamentary Group on Sickle Cell and Thalassaemia, 2021; 2018).
Pathophysiology of haemoglobinopathies
Normal haemoglobin
Normal RBCs are round, flexible biconcave discs, with a central indentation. Each RBC contains millions of haemoglobin molecules. Haemoglobin is made up of two parts:
- Haem – an iron compound that combines with oxygen;
- Globin – a protein.
RBCs are manufactured in the bone marrow and have a lifespan of approximately 120 days (Corrons et al, 2021). The main function of RBCs is transporting oxygen from the lungs to body tissues.
The globin protein is made up of two pairs of chains. The significant chains are:
- Alpha (α);
- Beta (β);
- Gamma (γ);
- Delta (δ).
Several haemoglobin types are produced during embryonic and subsequent stages of human development (Bain and Rees, 2025). Each type is made from different combinations of globin protein chains. The three types of haemoglobin that are most important are:
- Haemoglobin F – also known as foetal haemoglobin, this predominates during foetal development. The globin protein consists of a pair of alpha (α) and a pair of gamma (γ) globin chains (α2γ2);
- Haemoglobin A – this is the main type of adult haemoglobin (Fig 1) but is also synthesised during foetal life in tiny quantities. It is made up of a pair of alpha (α) and a pair of beta (β) globin chains (α2β2). After birth, synthesis of foetal haemoglobin declines, while adult type haemoglobin A increases. By one year of age most of the haemoglobin present in RBCs is haemoglobin A (Bain and Rees, 2025);
- Haemoglobin A2 – another adult type of haemoglobin, made in tiny quantities during foetal life and throughout adulthood, that is made up of a pair of alpha (α) and a pair of delta (δ) globin chains (α2δ2). It is inefficient at transporting oxygen but is useful for laboratory diagnosis of haemoglobinopathies.
Table 1 shows the proportion of these haemoglobins made at different stages of development.
Abnormal haemoglobin
In haemoglobinopathies, the structure or production of haemoglobin is altered due to genetic alterations (mutations) – see Box 1 for an explanation of terminology. Beta thalassaemia results in a lack of beta globin chains being made, while SCD causes the production of an altered version of the beta globin chain. In each case, the effect on the beta globin chain is caused by an alteration in the DNA sequence of the beta globin gene.
Box 1. Terminology
In the field of genetics and genomics, the term ‘variant’ describes an alteration in the expected DNA sequence. Reports from NHS genomic laboratories will report the presence or absence of a ‘pathogenic variant’ (an alteration in the DNA that has a clinical effect). However, in the clinical area of sickle cell disease and thalassaemia, ‘variant’ has a different meaning. ‘Haemoglobin variant’ used in this context refers to a sub-type of haemoglobin mutations, rather than the genetic alteration. Therefore, in this article, ‘genetic alteration’ describes the DNA sequence, and ‘haemoglobin variant’ describes the clinical sub-types of haemoglobin.
Inheritance of haemoglobinopathies
The role of genes, proteins and chromosomes
A gene is the sequence of DNA that provides the instructions for a cell to make a particular protein, including the beta globin chains. Genetic alterations in the beta globin gene can result in a haemoglobinopathy. What type of haemoglobinopathy depends on the genetic alteration, or combination of alterations, in the beta globin gene and how these affect the protein produced. These fall into one of two categories, based on their effect on the beta globin protein:
- Quality’ alterations that affect the structure of the beta globin chain;
- Quantity’ alterations that affect the amount of protein made.
DNA strands form chromosomes. People typically have 46 chromosomes in 23 pairs, with one pair inherited from their mother and the other from their father; each pair of chromosomes has the same DNA sequence, giving rise to gene pairs (Knight and Andrade, 2018). The gene for beta globin is on Chromosome 11, and each person has two copies of the beta globin gene, one on each copy of Chromosome 11 (Ali et al, 2021). The two copies of the beta globin gene are described using the short-hand notation of ββ.
Inheritance pattern
Beta thalassaemia and SCD are known as autosomal recessive conditions and affect males and females equally. This means both copies of the beta globin gene need to have a genetic alteration for the person to show clinical signs and symptoms of the condition (see Fig 2 for an overview of autosomal recessive inheritance).
If only one copy of the gene has an alteration, the person is a ‘carrier’ for the condition; a sickle cell carrier has the symbol AS and a beta thalassaemia carrier is designated as AβThal. In most cases, carriers are not affected clinically, although there are some rare exceptions to this rule (Weatherall and Clegg, 2001).
More people are carriers for the condition than have the condition itself. The proportion of people who are carriers is referred to as carrier frequency. SCD and thalassaemia are more common in certain ethnic groups (Table 2).
16 June, 2025 By Michelle Bishop, Lola Oni, Joan Walters and Emma Tonkin
Understand the causes, disease processes and presenting symptoms of the inherited blood disorders, sickle cell and thalassaemia. This is a Self-assessment article and comes with a self-assessment test
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Abstract
A haemoglobinopathy is an inherited blood disorder, affecting the haemoglobin which carries oxygen in red blood cells. In the UK, the two most common haemoglobinopathies are sickle cell disease and beta thalassaemia. This article, the first of four in a series on sickle cell disease and beta thalassaemia, outlines their genetic inheritance, pathophysiology, clinical manifestation and complications. Other articles in the series will focus on nursing assessment and clinical management, along with revised genetic competencies for generalist midwives and midwives and nurses specialising in this area.
Citation: Bishop M et al (2025) Understanding the key features of sickle cell disease and beta thalassaemia. Nursing Times [online]; 121: 7.
Authors: Michelle Bishop is associate director, learning and training at Wellcome Connecting Science; Lola Oni is freelance specialist nurse consultant and lecturer; Joan Walters is senior practitioner lecturer at King’s College London; Emma Tonkin is associate professor at University of South Wales
This article has been double-blind peer reviewed
Scroll down to read the article or download a print-friendly PDF here (if the PDF fails to fully download please try again using a different browser)
Assess your knowledge and gain CPD evidence by taking the Nursing Times Self-assessment test
Introduction
Sickle cell disease (SCD) and beta thalassaemia belong to a group of inherited conditions known as haemoglobinopathies, where the haemoglobin in red blood cells (RBCs) is affected by a genetic alteration in the globin genes. This results in an abnormal structure or reduced production of haemoglobin, which can cause chronic anaemia and other serious health problems. Each year, around 245 babies are diagnosed with a clinically significant haemoglobinopathy through the newborn screening programme in England (NHS England, 2022).
SCD and beta thalassaemia are the two most common haemoglobinopathies (Pecker et al, 2019); they are also among the most common inherited conditions in the UK (National Institute for Health and Care Excellence 2025). In May this year, there were an estimated 17,653 people with SCD and 2,561 with clinically significant beta thalassaemia on the National Haemoglobinopathy Register (2025). However, as not all individuals are registered, the real number is likely to be higher, with efforts ongoing to establish a database for more accurate reporting.
SCD and beta thalassaemia are life-long conditions. SCD causes RBCs to become sickle-shaped, while beta-thalassemia leads to reduced production of normal haemoglobin. While both diseases can lead to chronic anaemia, they are multi-systemic and, in the case of SCD, complications can happen quickly and unexpectedly (Hackett, 2021).
The age that people present with clinical symptoms depends on many factors, including the type of genetic alteration inherited, environment, access to preventive care and prompt management of acute symptoms and illness.
The multi-systemic nature of SCD and beta thalassaemia, and the fact that they are relatively common inherited blood disorders, means all nurses and midwives should be aware of these conditions and how to provide effective care and support to affected individuals and their families. However, evidence suggests that there can be deficits in practitioners’ knowledge, skills and attitudes in caring for individuals with these conditions and that in the case of SCD, these have contributed to avoidable complications, morbidity and mortality (Sickle Cell Society 2023; All-Party Parliamentary Group on Sickle Cell and Thalassaemia, 2021; 2018).
Pathophysiology of haemoglobinopathies
Normal haemoglobin
Normal RBCs are round, flexible biconcave discs, with a central indentation. Each RBC contains millions of haemoglobin molecules. Haemoglobin is made up of two parts:
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Haem – an iron compound that combines with oxygen;
Globin – a protein.
RBCs are manufactured in the bone marrow and have a lifespan of approximately 120 days (Corrons et al, 2021). The main function of RBCs is transporting oxygen from the lungs to body tissues.
The globin protein is made up of two pairs of chains. The significant chains are:
Alpha (α);
Beta (β);
Gamma (γ);
Delta (δ).
Several haemoglobin types are produced during embryonic and subsequent stages of human development (Bain and Rees, 2025). Each type is made from different combinations of globin protein chains. The three types of haemoglobin that are most important are:
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Haemoglobin F – also known as foetal haemoglobin, this predominates during foetal development. The globin protein consists of a pair of alpha (α) and a pair of gamma (γ) globin chains (α2γ2);
Haemoglobin A – this is the main type of adult haemoglobin (Fig 1) but is also synthesised during foetal life in tiny quantities. It is made up of a pair of alpha (α) and a pair of beta (β) globin chains (α2β2). After birth, synthesis of foetal haemoglobin declines, while adult type haemoglobin A increases. By one year of age most of the haemoglobin present in RBCs is haemoglobin A (Bain and Rees, 2025);
Haemoglobin A2 – another adult type of haemoglobin, made in tiny quantities during foetal life and throughout adulthood, that is made up of a pair of alpha (α) and a pair of delta (δ) globin chains (α2δ2). It is inefficient at transporting oxygen but is useful for laboratory diagnosis of haemoglobinopathies.
Table 1 shows the proportion of these haemoglobins made at different stages of development.
Abnormal haemoglobin
In haemoglobinopathies, the structure or production of haemoglobin is altered due to genetic alterations (mutations) – see Box 1 for an explanation of terminology. Beta thalassaemia results in a lack of beta globin chains being made, while SCD causes the production of an altered version of the beta globin chain. In each case, the effect on the beta globin chain is caused by an alteration in the DNA sequence of the beta globin gene.
Box 1. Terminology
In the field of genetics and genomics, the term ‘variant’ describes an alteration in the expected DNA sequence. Reports from NHS genomic laboratories will report the presence or absence of a ‘pathogenic variant’ (an alteration in the DNA that has a clinical effect). However, in the clinical area of sickle cell disease and thalassaemia, ‘variant’ has a different meaning. ‘Haemoglobin variant’ used in this context refers to a sub-type of haemoglobin mutations, rather than the genetic alteration. Therefore, in this article, ‘genetic alteration’ describes the DNA sequence, and ‘haemoglobin variant’ describes the clinical sub-types of haemoglobin.
Inheritance of haemoglobinopathies
The role of genes, proteins and chromosomes
A gene is the sequence of DNA that provides the instructions for a cell to make a particular protein, including the beta globin chains. Genetic alterations in the beta globin gene can result in a haemoglobinopathy. What type of haemoglobinopathy depends on the genetic alteration, or combination of alterations, in the beta globin gene and how these affect the protein produced. These fall into one of two categories, based on their effect on the beta globin protein:
‘Quality’ alterations that affect the structure of the beta globin chain;
‘Quantity’ alterations that affect the amount of protein made.
DNA strands form chromosomes. People typically have 46 chromosomes in 23 pairs, with one pair inherited from their mother and the other from their father; each pair of chromosomes has the same DNA sequence, giving rise to gene pairs (Knight and Andrade, 2018). The gene for beta globin is on Chromosome 11, and each person has two copies of the beta globin gene, one on each copy of Chromosome 11 (Ali et al, 2021). The two copies of the beta globin gene are described using the short-hand notation of ββ.
Inheritance pattern
Beta thalassaemia and SCD are known as autosomal recessive conditions and affect males and females equally. This means both copies of the beta globin gene need to have a genetic alteration for the person to show clinical signs and symptoms of the condition (see Fig 2 for an overview of autosomal recessive inheritance).
If only one copy of the gene has an alteration, the person is a ‘carrier’ for the condition; a sickle cell carrier has the symbol AS and a beta thalassaemia carrier is designated as AβThal. In most cases, carriers are not affected clinically, although there are some rare exceptions to this rule (Weatherall and Clegg, 2001).
More people are carriers for the condition than have the condition itself. The proportion of people who are carriers is referred to as carrier frequency. SCD and thalassaemia are more common in certain ethnic groups (Table 2).
If a couple who are carriers have children, there are four possible combinations of the genes that they can pass on, which means there is a one in four (25%) chance in every pregnancy of the child inheriting the condition (Fig 2). Couples who are carriers, with a chance of having a child with serious forms of beta thalassaemia or SCD, can have the foetus tested in the early stages of pregnancy to decide if they wish to continue or terminate an affected pregnancy (genetic competencies for practitioners when working in this area will be covered in article 4 of this series).
Beta thalassaemia
Genetic alterations
More than 200 different genetic alterations within the beta globin gene are known to cause beta thalassaemia (Ali et al, 2021). These DNA changes directly affect the quantity of beta globin chain made, ranging from a small reduction in the amount of protein being produced to no protein at all. The amount of beta globin chain made directly correlates to the severity of the condition (Taher et al, 2025).
Genetic alterations that result in no beta globin chain being made from that gene are known as beta zero alterations (β0). Genetic alterations that cause a reduction in the amount of beta globin chain made from a gene are referred to as beta plus (β+). As we all have two copies of the beta globin gene, it is the combination of the genes and their genetic alterations that determine how much beta globin chains are made in total and, therefore, how much haemoglobin A is present in the RBCs. This correlates to the clinical manifestation of the condition (Taher et al, 2025).
