Introduction

Thalassemia is an inherited disorder of the red blood cells. Specifically, it affects the haemoglobin molecule's ability to transport oxygen around the body. The severity of thalassemia can range from asymptomatic to requiring regular blood transfusions, a more serious manifestation labelled severe transfusion-dependent thalassemia (TDT). This condition significantly impacts mortality and morbidity in parts of the world, and research into its global impact and epidemiology is important to help prevent its continual spread. This article will provide background on thalassemia and its symptoms, causes, and global prevalence. Emphasising the importance of encouraging global health initiatives and improvements in healthcare for regions badly impacted by this disease.

Overview of thalassemias

Types of thalassemias

Thalassemia is categorised depending on which globin chain within the haemoglobin molecule is not being produced enough. The two most common types of thalassemia manifest due to a lack of alpha and beta globins, labelled alpha thalassemia and beta thalassemia, respectively.

• Alpha thalassemia is due to genetic mutations within the alpha globin genes. These mutations can occur in any number of the four alpha-globin genes and can reduce the amount of alpha globulins that are synthesised.² Depending on how many globins are deleted, the condition can be asymptomatic (that in which only one or two alpha globins are defective or cause more severe symptoms.³ The most severe being alpha-thalassemia hydrops fetalis, a condition in which all four globins are missing, often leading to death before birth¹
• Beta thalassemia is caused by genetic mutations within the beta globin gene. These can cause a reduced number or the complete absence of beta globin chains. Mutations can only occur in up to two of the beta globin genes. One defective gene causes no symptoms, and two defects cause either mild or more severe symptoms associated with the condition called beta thalassemia major. This condition often requires regular transfusions of red blood cells to provide the body's cells with sufficient oxygen³

Genetic basis

Thalassemia is a genetic condition that is autosomal recessive, meaning both parents must carry the mutated gene for the condition to be passed on to the child.² Alpha thalassemia occurs due to mutations on one or more genes on chromosome 16, and beta thalassemia occurs from mutations in one gene on each chromosome 11.³ 

As the number of mutated globins increases, so does the severity of the condition. Individuals may be carriers of the condition with no symptoms themselves or have severely symptomatic versions of the condition. 

Clinical impact

Thalassemia's direct impact on the body is caused by the disruption of the transportation of oxygen through the body within the bloodstream. Depending on the severity, it can massively reduce the oxygen concentration within the blood, resulting in mild to severe cases of anemia. The main symptoms of anemia are:

• Tiredness
• Dizziness
• Headaches
• Heart palpitations 
• Shortness of breath
• Pale skin
• Skin being cold to the touch

Anemia can have long-term complications for the heart, lungs, and hormonal systems. It can cause stunted growth, bone and body deformities, and disruptions in puberty.⁵ 

Furthermore, due to its implications for the endocrine organs, it can become a risk factor for the development of diabetes mellitus, hypothyroidism and hypoparathyroidism due to the implications it can have on the endocrine organs. These long-term complications can significantly impact the quality of life for individuals with thalassemia, highlighting the importance of early detection and comprehensive treatment strategies.⁴

Transfusion-dependent thalassemia, also known as Cooley’s anemia, can cause the accumulation of excessive iron in the body, causing iron overload. This can damage the heart, liver and endocrine organs.

Global prevalence

General statistics

Thalassemia affected over 1,300,000 people worldwide in 2021, and the World Health Organization declared it a major global health concern. It affects people all over the globe but is particularly present in parts of Africa, Southeast Asia and the Middle East.⁶ 

Global trends in prevalence have been associated with availability and quality of healthcare, migration and levels of awareness and action within societies' public health systems, however, such as the Northern parts of Europe and America. 

This is thought to be because of migration as a result of globalisation.⁷ Increases in awareness, screenings, and preventive methods in countries heavily impacted have reduced the thalassemia presence. As a result, the global landscape of this disease is gradually changing as time goes on, offering hope for the future. 

Risk factors

Many risk factors for thalassemia have emerged from research into the epidemiology of this disease. Thalassemia can be linked mainly to environmental, genetic and demographic factors, which determine its impact and rate of occurrence. 

Listed below are some of the main risk factors for thalassemia:

• Geographical location and prevalence of malaria - It has been documented that thalassemia may provide resistance to malaria, as the red blood cell defects interrupt the process in which the malaria parasite can bind to these cells. In areas of the world that have a high prevalence of malaria, thalassemia is often found to be more common. The thought process behind this is that the mutated genes that cause thalassemia may have become more prevalent as a form of natural selection in areas where malaria is very common⁷
• Cultural factors - Consanguineous marriage, that is, marriage to someone closely related to you, is common in the Middle East and parts of Africa and Asia. Around 10% of the global population is made up of couples who are closely related and their offspring. If a common ancestor had thalassemia, the likelihood of this faulty gene being present in both related individuals' DNA is high. The recessive nature of the faulty globin genes increases the chance that a child born to these parents will have thalassemia
• Healthcare infrastructure - Successful preventative measures for thalassemia include screenings for the genetic mutation and genetic counselling to help prevent the passing on of this gene. In high-income countries, this is readily available and has been seen to combat the prevalence of thalassemia. Genetic counselling, in particular, plays a crucial role in informing individuals about the risks and prevention strategies associated with thalassemia. Individuals living in lower-income countries do not have as much access to preventative measures or treatment options, leading populations to be impacted more severely by this condition

Strategies for control and prevention

Thalassemia is still a major cause for concern in many areas where populations are exposed to multiple risk factors for this condition. Current treatment options depend on the severity of the thalassemia. For mild cases, management of the symptoms of anemia with iron and vitamin supplementation may suffice. 

However, more serious iterations require lifelong management and hospital visits for blood transfusions or intensive iron level management.

This has a huge impact on the lives of people with thalassemia, taking both a mental and physical toll on patients as they have to come to terms with living with a debilitating lifelong condition. Some of the ways in which countries are tackling this major health concern are:

• Public health education programmes - Encouraging the implementation of educational programmes, especially in high-risk areas, can increase awareness of this condition and how to stop it spreading. For example, individuals who belong to communities where consanguinity is common. By educating these communities to make them aware of the risks involved with this type of procreation, they may make more efforts to partake in screenings or genetic counselling to lower the risk of passing on the condition. Educational programmes have succeeded in high-risk countries such as Greece, Italy and Cyprus.¹¹ Certain high-risk countries such as Iran have had to take more drastic measures to ensure the control of this disease, with mandatory premarital screenings for thalassemia being put in place⁸
• Healthcare advancements - Pioneering therapies for thalassemia are creating hope for those with more serious types of this condition. One very recent gene-editing therapy was approved in the UK in August 2024. This therapy offers a life-changing treatment for transfusion-dependent beta thalassemia, with 93% of patients not needing a transfusion for at least a year after receiving the treatment.⁹ Furthermore, chelation therapy is successfully used to avoid iron overloading from regular blood transfusions¹⁰ 
• In countries where these treatment options are readily available, the disease burden of thalassemia is massively reduced. Low-income countries, however, often lack the funding to implement these treatment programmes in their healthcare systems. This reduces the quality of life for people in these countries affected by thalassemia. Societies that do have access to these effective treatment options must make efforts to support countries in which this is not as readily available
• Global health initiatives - The World Health Organization is working with low-income countries and rural communities to try and alleviate the burden of blood disorders such as thalassemia. They do this by creating action plans to aid in the prevention, diagnosis and management of the main symptoms of thalassemia such as anemia. Furthermore, they help provide easy access to information about these conditions and their impacts on the world, spreading awareness and encouraging change. More global efforts are required to support countries heavily affected by thalassemia and similar conditions, aiming to reduce this disease's impact on the world

Summary

Thalassemia is a genetic disorder of the blood affecting its ability to provide the body with oxygen. This condition has varying levels of severity, ranging from asymptomatic to requiring almost constant medical intervention. It is considered a major concern to public health and is still a significant cause of mortality and morbidity in regions with limited access to healthcare and poor awareness surrounding this condition. Due to the genetic nature of the condition, it is essential that high-risk areas implement screening programmes and educate populations on this disease so they understand how it can be spread and what signs to look out for. Supporting healthcare systems in lower-income countries, investing in research into treatment options and implementing global health initiatives are essential to reducing the disease burden of thalassemia.