Science

Thalassemia: A Prevalent Yet Overlooked Genetic Disorder

I am sure you have heard about Thalassemia.

It’s so common that you will find it in school Biology textbooks, health magazines, newspapers, everywhere.

Almost 4.5% of the world population is affected by Thalassemia.

In India, more than 10000 Thalassemic children born every year.

Yet, it has not got the limelight. Until someone is affected, people rarely talk about it.

If you don’t know how it is to be a Thalassemic person then read on.

But wait before I go any further, you might think that why all of a sudden I have decided to write on Thalassemia?

Unless and until things (like Thalassemia) happen to our life or to the lives of our closed ones, we behave like it does not exist.

A few days back one of my friend’s closed one died due to Thalassemia. He was naturally devastated. He asked me to write about Thalassemia.

So that my readers can become more aware of it.

I know you and your family might not have witnessed thalassemia ever but you never know. Prevention is better than cure.

It’s always good to know about the problem and its solutions before it becomes part of your life.

You might have heard about the science of thalassemia but what’s more important to know is to know its implications and effect on society.

And how we can become part of the solution to prevent Thalassemia?

That’s what I will try to convey through this article.

What exactly Thalassemia is?

Thalassemia is a genetic blood disorder.

Our blood consists of different kinds of cells. As you know there are red blood cells (RBC), white blood cells (WBC), platelets. All of these cells have different functions.

These blood cells circulate with the plasma in the blood. (blood is made mostly of plasma).

Blood cells
Types of blood cells

The main job of red blood cells is to help in CO2 and O2 exchange.

Hemoglobin is the protein reside in red blood cells which transport O2 in all the tissues of the body.

The structure of hemoglobin is very interesting. Each hemoglobin molecule is consists of four heme groups surrounding a globin group.

Heme is composed of an organic compound known as porphyrin to which an iron (Fe) atom is attached.

This iron atom in heme binds with oxygen as the blood travels between the lungs and tissues.

This means, there are four iron atoms in each hemoglobin molecule and each hemoglobin can bind to four oxygen atoms.

See the image below. (a) is the structure of hemoglobin and (b) is the structure of heme.

Hemoglobin structure

People with thalassemia disorder are not able to make enough hemoglobin in their body. Which means the tissues of their body do not get enough oxygen. Organs become starved of oxygen and can not function properly.

This makes the thalassemic patient tired and pale all the time.

But why thalassemic patients are not able to make enough hemoglobin?

To know this, we have to know a little more detail about hemoglobin.

In a healthy person’s body, three types of hemoglobins are present.

Hemoglobin A (almost 95%), hemoglobin A2 (2-3%), and hemoglobin F (<1%)

Hemoglobin A is majorly present in any healthy person’s body.

The different hemoglobins are made of varied combinations of the globin chains. For example hemoglobin A is made of 2 alpha and 2 beta-globin chains.

Look at the image below.

Hemoglobin synthesis

The genes controlling globin production are on chromosome 16 (for alpha-globin) and 11 (rest of the globin).

Now it’s important to know how these globins are produced in the human body over a period of time.

See the below diagram-

Different hemoglobin synthesis diagram
Image from thalessemia.com

As you can see in the diagram, the production of the alpha-globin molecule remains constant throughout our life.

The beta-globin appears early in fetal life at low levels and then rapidly increases after 30 weeks. Then beta-globin production remains constant thereafter.

With gamma-globin, the case is opposite.

The delta globin appears at a low level in fetal life and maintains a low profile throughout life.

That means after birth we have more alpha and beta-globin production than gamma or delta globin.

That is why hemoglobin A is present majorly in red blood cells. Because hemoglobin A is consists of 2 alpha and 2 beta-globin chains.

In a thalassemia patient, mutation (mutation is a phenomenon that leads to permanent alteration in the DNA sequence that makes up a gene) or deletion (loss of genetic material) of the genes that control globin production occurs.

Based on this, thalassemia is classified into two types.

beta thalassemia and alpha thalassemia.

In beta-thalassemia, the production of beta-globin decreases due to mutation or deletion of respective genes.

As a result, the alpha-globin becomes excess. Due to the scarcity of beta-globin, alpha-globin prefers to pair with itself and form a tetramer of 4 alpha-globins.

Or two alpha and two delta-globin can pair to form an excess of hemoglobin A2 (which normally should be 2-3% in the blood).

This leads to complications in the function of cell maturation and cell membrane functions.

Remember normally in a healthy person two alpha and two beta-globin pairs to form hemoglobin A.

Beta-thalassemia can be divided into two types, major and minor beta-thalassemia.

What decides the major or minor beta-thalassemia?

We have a homologous pair of each chromosome in our body. One comes from mother and one from father.

So for beta-globin, we have two chromosomes (chromosome 11) that can produce it.

In scientific terms, we have two alleles.

An allele is a variant form of a gene. Humans have two alleles at each chromosome, with one allele inherited from each parent. 

If mutation or deletion occurs at only one allele then it’s called minor beta-thalassemia.  In this condition, the amount of beta-globin in the cell is reduced by half.

People suffering from minor beta-thalassemia show no symptoms. They lead a normal life. But they are carriers of thalassemia and can transfer this to their children.

However, if a mutation or deletion happens at both allele (of the beta-globin forming gene) then no beta-globin protein form and this condition is called major beta-thalassemia.

This condition is also known as Cooley’s anemia which is a severe form of anemia.

Similarly, alpha-thalassemia occurs due to the shortage of alpha-globin production.

Two genes (means four alleles located at chromosome no. 16) are responsible for the formation of alpha-globin production.

Again due to some malfunction (mutation) these genes can reduce or stop the formation of alpha-globin.

Now, due to shortage of alpha-globin, beta-globin will start pairing with itself and form tetramer of four beta-globin.

The hemoglobin that this tetramer will form is known as hemoglobin H. This generally leads to shortening the life span of red blood cells.

Normally life span of red blood cells is 120 days but in a thalassemic patient, it reduces to 20 days.

Each parent potentially passes two of their four alpha-globin genes (or alleles) to the offspring. So two from father and two from mother.

Just like beta-thalassemia, alpha-thalassemia can be major or minor.

If one of the genes among four is mutated or deleted then it’s the case of minor alpha-thalassemia.

In this condition, the person will be normal and won’t show any symptoms. He only becomes the carrier of thalassemia.

On the other hand, if two or more than two genes (of alpha-globin forming genes) get mutated or deleted then it becomes major alpha-thalassemia.

Now suppose you are suffering from minor thalassemia and you marry someone who also has minor thalassemia.

What are the chances that your children will have major thalassemia?

25%.

Thalassemia carrier diagram

Most importantly, there is a 50% chance that your children will be a carrier of thalassemia.

There will always be a risk of having major thalassemia to some children in your family down the line.

If you have seen someone with major thalassemia condition, you know it’s not fun.

There is no suitable treatment available for thalassemia.

One can manage thalassemia by regular blood transfusions. Imagine if you have to take blood every month to stay alive.

Due to regular blood intake, excess iron gets deposited in the heart, liver, and other organs of the body. To remove excess iron-chelating agents are used.

Bone marrow transplant might be a possible treatment but matching bone marrow is a very difficult process. Moreover, it is an expensive treatment.

If you have read up to here then thank you.

I hope you have understood the severity of thalassemia.

What you can do to prevent thalassemia?

Please get yourself tested. A simple health check-up can tell you whether you are a thalassemia carrier or nor.

Especially before marriage, you must check whether you and your partner are thalassemia carriers.

Birth of a thalassemia major children can only be prevented by knowing the thalassemia status of the parents before the child is conceived.

If both parents found positive for the carrier state, they need to counseled for prenatal diagnosis. That is a different topic to discuss. I am not going into detail.

My sole purpose for writing this article is to make you aware of thalassemia. Maybe you have read about it but never thought about its severity.

We think that medical science has become so advanced that we can cure almost any disease.

Cancer is perhaps the only disease we are very afraid of. But there are many more for which no appropriate treatment is available.

We can only try to prevent them. Thalassemia is one of them.

And it is a very common genetic disorder. More than 10000 major thalassemic children born in India every year.

That means more than 10000 children need blood every month. Imagine what goes through their family.

Yet the awareness about thalassemia is so low in our society. It’s an overlooked topic.

We can prevent thalassemia by getting ourselves tested.

Can I ask you a favor?

Please discuss thalassemia with your spouse, girlfriend, friend, or family whenever possible.

Donate blood whenever possible. Your blood can increase the lifespan of a thalassemic children.

Every child deserves to live a healthy life.

Don’t let a child suffer because of your ignorance.

Do you want to say anything? Let me know in the comment section.

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Have a wonderful week. Until next time.

Joy

Source:

  1. Thalassemia .com
  2. What is thalassemia-CDC
  3. Harvard.edu
  4. Hemoglobin-Britannica.com

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