This is the first part of our series about the condition based on our patient booklet “Fast Facts for Patients: Beta Thalassemia”. This article shows what beta thalassemia (BT) is and what causes it.

First, the Facts

1. Beta thalassemia (BT) is a blood condition you’re born with. It affects your red blood cells.
2. BT is a disease caused by changes (mutations) in genes that are passed on from parent to child. You have BT when you inherit a gene change from both of your parents.
3. There are two types of BT disease – BT major and BT intermedia. A person can also be a healthy carrier of BT without having the disease. This is called BT trait (or BT minor).
4. Treatment depends on the type of BT disease you have. People with BT major will require regular blood transfusions throughout their life.
5. New treatments for BT have recently been approved or are being tested in clinical trials around the world, with promising results.

What Is Beta Thalassemia?

Thalassemia is a condition you are born with. It affects red blood cells. There are two main types: alpha thalassemia and beta thalassemia (BT). This booklet is about BT.

In BT, the body doesn’t make enough normal hemoglobin (Hb). Hb is the protein in red blood cells that enables them to carry oxygen around the body. There are also too few healthy red blood cells.

This is called anemia. Anemia can be mild or serious. Serious anemia can damage organs and can be fatal.

Types of BT

There are different types of BT. How severe your condition is and how bad your symptoms are depends on the type you have. You may have no symptoms, or you may need lifelong treatment.

Why Isn’t the Hemoglobin Made Properly?

Each molecule of normal adult Hb is made up of four protein chains – two alpha chains and two beta chains. If you have BT, your body is not producing enough of the beta chain. That means you cannot make enough normal Hb, so less oxygen can be carried around your body.

What Causes Beta Thalassemia?

BT is a genetic condition. This means it is caused by a change (also called a mutation) in a gene. There can be different types of change – some cause the beta chains of Hb to be missing completely, while others cause a decrease in beta chain production.

What Are Genes?

Your genes carry instructions for the growth, development and function of your entire body.

Genes are found on chromosomes. Every cell in the human body has 23 pairs of chromosomes – so 46 chromosomes in total. Every chromosome has anywhere from 55 to 20 000 genes.

Genes are in pairs too – you inherit one copy from your mother and one copy from your father. A pair of genes is carried on a pair of chromosomes (one gene on each chromosome).

Each pair of genes carries the code to make a single protein.

The gene that carries the instructions for making the beta chain protein of Hb is called HBB.

Who Gets BT?

BT is more common in some parts of the world where malaria is, or has been, a problem (for example, the Mediterranean, the Middle East, North Africa, India and Southeast Asia) and in people with ancestry originating from these areas. This is because the gene changes that cause BT also give some protection against malaria.

Over time, the proportion of people in the population with a BT gene change has increased and, as people migrate around the world, BT has become more common in other regions too.

Inheriting Beta Thalassemia

BT is nearly always a recessive genetic condition. In recessive conditions, both genes in a pair have to be affected to produce disease. This means you have to inherit a mutated gene from both of your parents to have the condition. So, either your parents have BT themselves, or, more commonly, they are ‘carriers’ of a mutated HBB gene.

Carriers have one mutated HBB gene and one healthy HBB gene. Because they have one healthy gene, they can still make enough healthy Hb beta chain protein. They will never develop BT, but they can pass on the mutated gene to their children.

Being a carrier of a single mutated HBB gene is called beta thalassemia trait or beta thalassemia minor.

How Do Gene Changes Cause Beta Thalassemia?

There are many different changes to the HBB gene that can cause BT. How severely you are affected will depend on the type of gene change that you have. There are two main types of changes:

• Those that result in less beta chain protein than normal being made. Doctors write this as β+.
• Those that result in no beta chain protein being made. Doctors write this as β0.

Because there are two HBB genes, a person can have a combination of these types of change. You may have β+/β+, β+/β0 or β0/β0.

If only one gene of the pair is affected (BT trait), you may have β+/β or β0/β.

There is another possible gene change, called HbE. This results in the production of an abnormal type of Hb known as hemoglobin E. So, you can also have the gene combinations β+/E+ or β0/E+.

Information based on Fast Facts for Patients: Beta Thalassemia (Karger, 2023).