What Is Beta Thalassemia

Overview

Beta-thalassaemia is an inherited genetic disorder that restricts the body’s ability to synthesise haemoglobin, a protein in red blood cells that is needed to transport oxygen around the body.¹ Haemoglobin is made of two basic components:  “Haem” (a compound containing iron that gives red blood cells their characteristic red colour) and “Globin” (a type of protein).² An alteration or mutation in the genes that produce the chain-like component of the globin protein (known as beta-globin chains) in red blood cells will reduce the number of red blood cells being made by the body. This occurrence causes beta-thalassaemia.^{1,2 1,2}  

There are three kinds of beta-thalassemia: Beta-thalassaemia major, Beta-thalassaemia intermedia, and Beta-thalassaemia minor.^1,3 Beta-thalassemia major is the most common and severe form of the disorder, whereas beta-thalassemia minor is the least common form of the disorder with almost unnoticeable symptoms (asymptomatic).^2,3 Beta-thalassaemia affects about 1 in 100,000 individuals in England itself, with specific ethnic communities such as Mediterranean, South Asian, South East Asian and Middle Eastern origin at a higher risk of being born with this condition. In the UK, beta-thalassaemia major has been reported more commonly in ethnic minority populations, the largest groups being of Indian, Cypriot, Bangladeshi, and Pakistani origin.

People with beta-thalassemia may present with different symptoms and severity based on the sub-type the individual may have. A diagnosis of beta-thalassemia is based on the results of a complete blood count.³ For patients with more severe forms of Beta-thalassemia, life-long treatment in the form of blood transfusion and medication, as well as lifestyle support, may be needed. In contrast, individuals with mild to no symptoms may require no intervention.^1,3 Previously, the overall survival of patients with beta-thalassemia major prior to the 21st century was as low as 50%. However, with advances in medical treatment, about 80% of patients now live beyond 40 years of age.³ Nonetheless, some of the complications that arise may be severe, and early diagnosis with a good care plan followed up by a qualified healthcare professional is key for patients with Beta-thalassaemia.³

Types of beta thalassaemia

To understand the types of Beta-thalassemia, it is important to look at how genes contribute to this condition.  The set of genes that help in the formation of the Beta-globin chains are called beta-globin genes. In the absence of the beta-globin genes, there will be no production of haemoglobin as there is no beta-globin chain production.² Beta-globin genes are inherited from both biological parents, and the summative effect of these genes determines how our haemoglobin is made throughout our lives.²

Based on the severity of the mutation in these genes, Beta-thalassaemia is classified  into three types:^1,3

1. Beta-thalassaemia Major (Also known as Mediterranean or Cooley’s anaemia)

This is the most severe type of beta-thalassemia. This is caused by either the complete absence of beta-globin genes or a defect in both beta-globin genes inherited from both parents. (homozygous form).^1,3 Patients typically undergo lifelong blood transfusions as treatment.

• Beta-thalassaemia intermedia

As its name suggests, patients with beta-thalassemia present with mild to moderate symptoms of anaemia.³ Both sets of beta-globin genes are defective but not completely absent. ³

• Beta-thalassemia minor

Individuals with Beta-thalassemia minor are commonly asymptomatic or report only mildly anaemic symptoms.^1,3 These individuals typically inherit only one defective gene while the other gene remains unaffected, resulting in only minor disruptions to haemoglobin synthesis (heterozygous).

Beta-thalassemia is purely genetic in origin (autosomal recessive pattern); thus, family history and ancestry, including being of Mediterranean, South Asian, South East Asian, African and Middle Eastern origin, remain the only known risk factors for disease onset.^1,3,4 

The risk of passing on beta-thalassemia varies. Beta-thalassaemia major parents have a known and fixed probability (50%) of passing one affected gene to their offspring. In comparison, beta-thalassaemia minor parents have only a 25% probability of passing the affected gene onto their offspring.⁴ For further advice and guidance around this, we advise you to speak to your GP surgery or diagnosing clinician.

Signs and symptoms

Signs and symptoms of Beta-thalassaemia vary based on the specific type.⁵

Beta-thalassemia minor individuals may not show symptoms throughout life or may report only minor or mildly anaemic symptoms, including such as:⁵

• Fatigue
• Weakness or Dizziness
• Paleness of the skin
• Frequent headache

Individuals with Beta-thalassaemia major tend to develop symptoms earlier in their life, and the symptoms are generally more severes:⁵

• Poor Appetite
• Susceptible to repeated infections or compromised immunity
• Slowed or delayed growth
• Abdominal swelling
• Pale, jaundiced, or yellowed skin

Without treatment, vital organs such as the spleen, liver and heart may undergo a harmful increase in size. Bones will become brittle, thin and deformed over time.⁵ Individuals with Beta-thalassaemia major rely on blood transfusions throughout their lifetime and may have a shorter life expectancy. Repeated blood transfusions may lead to iron accumulation in the heart and other vital organs. This could lead to heart failure as early on as their teens or early 20s.⁵

For individuals with Beta-thalassaemia intermedia, symptoms may vary from being mild or asymptomatic to severe and widespread, such as those seen in Beta-thalassaemia major.⁵

Diagnosis

Given the generic nature of the symptoms, beta-thalassaemia is mostly diagnosed incidentally. ^1-3 Family history of beta-thalassemia is the only known risk factor in determining predisposition towards Beta-thalassaemia.^3,4 Most individuals are commonly diagnosed between ages 6 and 12.

The following medical tests are commonly used to diagnose Beta-thalassaemia:^2,3,5

• Complete Blood count (commonly known as a blood test)
• Haemoglobin electrophoresis with haemoglobin F and A2 quantitation
• Reticulocyte count
• Molecular genetic testing
• Liver Function tests
• Bone marrow examination

In pregnant people, screening for thalassaemia is done using Chorionic Villus Sampling (CVS) and Amniocentesis.

Management of beta thalassaemia

Management of Beta-thalassaemia differs based on the type of beta-thalassemia and individual has and the severity of their symptoms.⁶ Common treatment options for managing beta-thalassaemia include:^3,6

1. Blood transfusions: In individuals with severe anaemia, blood transfusions may be required every 4-6 weeks to maintain steady haemoglobin levels.
2. Folic acid supplements to maintain bone marrow health.
3. The removal of spleen (Splenectomy) might be needed in children above 6 years of age, since splenic sequestration may contribute to shorter life spans of red blood cells.
4. Monitoring iron levels is crucial in individuals with Beta-thalassaemia undergoing repeated blood transfusions. Iron overload due to repeated blood transfusions can be prevented and managed using oral or intravenous chelation therapy (desferrioxamine mesylate).³
5. Stem cell transplantation from the bone marrow of an appropriately matched donor is a treatment modality that has been widely researched to expand the patient cohort that is able to receive this procedure as a treatment.⁷
6. Research has also indicated that stem cell transplantation from umbilical cord blood has been helpful in treating thalassaemia.⁸
7. Gene therapy may be a viable treatment option in the future for managing Beta-thalassaemia.

Follow-up for patients with beta-thalassaemia is mandatory and may be required as frequently as once a month.³ For patients older than 10 years of age, more advanced health checks and screening may be required annually.³ Further treatments for anaemic symptoms and vitamin and mineral deficiencies are prescribed when needed..³

Asymptomatic or mildly symptomatic individuals do not commonly require treatment, but genetic counselling should be encouraged to explain the genetic implications of beta-thalassemia, especially for individuals of childbearing age.^1,3  

Possible complications

The most commonly noted complication of Betathalassaemia is an overload of iron due to repeated blood transfusions.^1,8 This excess iron can accumulate in vital organs within the body, such as the liver, heart, and pancreas.^1,5 In severe cases, excess accumulation of iron may be fatal.^1,5

Thrombotic (blood clotting) events are a possible complication in beta-thalassaemic individuals. This event is caused by altered blood composition, which allows the formation of blood clots more readily³ This complication has been commonly reported in individuals with beta-thalassaemia intermedia due to lower levels of proteins C and S as well as increased D-dimer levels.³

Other complications noted in beta-thalassaemia include chronic hepatitis, cirrhosis, hypersplenism, HIV infection, and osteoporosis.^5,8

FAQs

How can I prevent beta thalassaemia?

Beta-thalassemia is a hereditary disorder that cannot be prevented or avoided.^1,3,4

Can beta thalassaemia be cured?

Currently, there is no cure for Beta-thalassaemia since it is a genetic disorder. There are some emerging treatment options, such as bone marrow stem cell transplantation, cord blood transfusion, and gene therapy, that are undergoing more research to validate efficacy.^5,8

When should I see the doctor?  

Signs and symptoms of Beta-thalassaemia may be non-specific; therefore, if you or someone that you know are experiencing the signs and symptoms above, especially in children, it would be advisable to visit your GP surgery as soon as possible.^1,8

Summary

Beta-thalassaemia is an inherited genetic disorder that reduces the ability to synthesise haemoglobin.¹ There are 3 types of beta-thalassemia based on the severity and number of the genetic mutations found on the beta-globin genes: Beta-thalassaemia major, Beta-thalassaemia intermedia, and Beta-thalassaemia minor.^1,3 Beta-thalassaemia major is a common and severe form, while Beta-thalassaemia minor is a mild asymptomatic type.^2,3 Family history and ancestry, including Mediterranean, South Asian, South East Asian, African and Middle Eastern descent, are the only risk factors of beta-thalassemia ^1,3,4 While the severity of signs and symptoms vary based on type, some commonly noted signs and symptoms include fatigue, dizziness, frequent headaches, poor appetite, jaundiced skin, increased pallor and compromised immunity.^3,5 Diagnosis typically requires laboratory tests such as complete blood count, liver function tests, and haemoglobin electrophoresis.^2,3,5 In pregnant individuals,  screening for thalassaemia is done using Chorionic Villus Sampling (CVS) and Amniocentesis. Beta-thalassaemia can be managed with blood transfusion,  monitoring iron levels, and surgical/medical intervention.^1,6 Possible complications include iron overload, increased blood clots, chronic hepatitis, cirrhosis, hypersplenism, HIV infection, and osteoporosis.^5,8