Causes of Thalassemia

Thalassemia is a genetic blood disorder that affects the body’s ability to produce hemoglobin, the protein in red blood cells responsible for carrying oxygen throughout the body. This condition can lead to anemia, fatigue, and other complications if left untreated. While thalassemia is widely known in regions such as South Asia, the Mediterranean, and parts of Africa, many people remain unaware of what causes this condition in the first place.

Unlike many other diseases that arise from lifestyle choices or environmental exposure, thalassemia is purely genetic, meaning it is passed down from parents to children through specific mutations in the DNA. These mutations affect the production of hemoglobin essential components either the alpha or beta protein chains leading to imbalances in red blood cell formation.

What is Thalassemia?

Thalassemia is a group of inherited blood disorders that affect the synthesis of hemoglobin. Hemoglobin is made up of two types of protein chains: alpha (α) and beta (β). Thalassemia occurs when there is a mutation in the genes responsible for producing one or both of these protein chains. Depending on which chain is affected, the condition is classified as either alpha thalassemia or beta thalassemia.

The severity of the disease can range from mild to severe, and it often depends on how many genes are mutated. The most severe forms such as beta thalassemia major (also known as Cooley’s anemia) can lead to life-threatening complications and require regular blood transfusions.

Causes of Thalassemia

1. Genetic Inheritance :- The root cause of thalassemia lies in genetics. It is an autosomal recessive disorder, which means that a child must inherit the faulty gene from both parents to develop the disease. If only one gene is inherited, the person becomes a carrier (also known as having thalassemia minor) and usually experiences mild or no symptoms. Humans have two copies of each gene one from each parent. In thalassemia, mutations occur in the genes that instruct the body to make the alpha or beta globin chains of hemoglobin. These mutations disrupt the production of the chains, leading to an imbalance that results in anemia and other symptoms. For instance, in beta thalassemia :-
   • If one beta globin gene is mutated, the individual has beta thalassemia minor.
   • If both beta globin genes are mutated, the individual has beta thalassemia major or intermedia, depending on the nature of the mutations.
     

   Similarly, in alpha thalassemia, the severity depends on how many of the four alpha globin genes are affected. If all four are defective, the result can be a fatal condition known as hydrops fetalis.

2. Genetic Mutations Behind Thalassemia :- Thalassemia is caused by mutations in specific genes responsible for hemoglobin production. In beta thalassemia, the gene responsible is HBB, located on chromosome 11. In alpha thalassemia, the genes affected are HBA1 and HBA2, located on chromosome 16.These genetic mutations can vary in nature. Some are deletions of parts of the gene, while others are point mutations that alter a single base pair in the DNA sequence. The mutations hinder the body’s ability to produce functional hemoglobin, causing red blood cells to become fragile and break down faster than normal.Over time, this leads to chronic anemia and a need for medical interventions like transfusions, iron chelation therapy, and sometimes bone marrow transplantation.
3. Carrier Status and Thalassemia Trait :- One of the reasons thalassemia continues to be prevalent in certain populations is due to the high number of carriers. People who are carriers usually don’t exhibit major symptoms, so they may not be aware they carry the gene. However, if two carriers have children, there is :-
   • A 25% chance that the child will have thalassemia major
   • A 50% chance that the child will be a carrier
   • A 25% chance that the child will be completely unaffected

   This makes genetic counseling and premarital screening crucial in communities where thalassemia is common. Early diagnosis through blood tests or prenatal screening can help couples make informed reproductive choices.

4. Geographic and Ethnic Influence :- Thalassemia is more commonly seen in people from certain geographic and ethnic backgrounds. This includes individuals of :-
   • South Asian
   • Mediterranean (especially Italian and Greek)
   • Middle Eastern
   • African
   • Southeast Asian descent
     

   Historically, the gene mutations responsible for thalassemia may have offered some resistance to malaria, which was prevalent in these regions. As a result, the carrier frequency increased in those populations. This phenomenon is a classic example of balanced polymorphism, where being a carrier provided a selective advantage against another disease.

Can Thalassemia Be Prevented?

Since thalassemia is a genetic condition, it cannot be “prevented” in the traditional sense. However, carrier detection, prenatal testing, and genetic counseling can significantly reduce the incidence of severe cases. These preventive measures are especially important in high risk populations.

Couples who are both carriers of thalassemia should be offered genetic counseling to understand their reproductive options. In vitro fertilization (IVF) combined with preimplantation genetic diagnosis (PGD) allows the selection of embryos without the thalassemia mutation.

Importance of Early Diagnosis of Thalassemia

Understanding the causes of thalassemia reinforces the importance of early diagnosis. A simple blood test can detect abnormal hemoglobin levels and prompt further genetic testing if thalassemia is suspected. In many countries, newborn screening programs have been implemented to identify affected infants early, allowing for timely treatment and better long term outcomes. Early diagnosis also helps in managing complications associated with the condition, including :-

1. Growth delays
2. Bone deformities
3. Iron overload
4. Organ damage

With the right care plan, individuals with thalassemia can lead healthy and productive lives.

Conclusion

Thalassemia is a serious yet manageable genetic blood disorder rooted in inherited mutations that affect hemoglobin production. Understanding its causes helps raise awareness and improve early detection and prevention strategies, especially in regions where the condition is prevalent.