Thalassemia: what it is, how it is inherited, and why screening is essential

Thalassemia is an inherited disorder characterized by chronic anemia caused by a defect in the production of hemoglobin, the protein responsible for transporting oxygen throughout the body.

“Hemoglobin is made up of 4 protein chains (2 alpha and 2 beta): when one of these is altered, it is referred to respectively as alpha- or beta-thalassemia.

It is not a rare condition: approximately 7% of the world’s population is affected, and in Italy around 7,000 people live with the disease. Its distribution is not uniform, being more common in Mediterranean countries, the Middle East, Asia, and Africa,” explains Professor Ferrari.

Thalassemia is inherited in an autosomal recessive pattern. This means that each individual has 2 copies of the beta-globin gene, one inherited from the mother and one from the father, and the disease develops only when both copies are altered.

When both parents are healthy carriers, each parent randomly passes on one of their 2 gene copies (either the normal or the altered one) to the child. As a result, with every pregnancy there are 4 possible combinations:

• in 3 cases, the child is not affected by the disease (the child may either be healthy or a healthy carrier);
• in only 1 case does the child inherit both altered copies and develop thalassemia.

For this reason, as Professor Ferrari points out, a couple in which both parents are healthy carriers has a 1 in 4 chance of having a child affected by the disease.

Healthy carriers, despite having a genetic mutation, generally do not show significant symptoms and lead normal lives.

In the most severe forms, particularly beta-thalassemia major, symptoms appear very early in life.

“The most severe form of beta-thalassemia appears as early as 6 months of age and can be fatal if not treated with chronic transfusions and iron chelation therapy,” treatment required to prevent iron overload caused by repeated transfusions, as chelating agents bind excess iron and help eliminate it from the body.

This occurs because after the first months of life, fetal hemoglobin is replaced by adult hemoglobin, which is defective in affected patients. This leads to severe anemia requiring immediate treatment.

The diagnosis of thalassemia is based on laboratory tests and, when necessary, genetic testing. The main investigations include:

• complete blood count (CBC) and hematocrit;
• hemoglobin analysis;
• genetic testing to identify mutations.

As Professor Ferrari emphasizes, there are more than 400 mutations associated with thalassemia, although in Italy the most common ones are few and well known. In uncertain cases, more in-depth genetic analyses are performed.

Anemia is often the first warning sign: the first symptom is anemia, so a simple blood test is enough to begin further investigations.

As a genetic disease, thalassemia screening is particularly important for at-risk couples.

“Because it is a hereditary disease, screening can be performed prenatally, and in any case in all children born to parents who are both carriers of the disease.”

Screening can be performed:

• before birth, through prenatal diagnosis (for example, chorionic villus sampling);
• at birth or during the first months of life, in children born to carrier parents;
• before pregnancy, in individuals from high-prevalence areas or with a family history of the disease.

Patients with severe forms require regular transfusions and lifelong iron chelation therapy to prevent iron accumulation in the body.

Care involves multiple specialists, including hematologists, cardiologists, and endocrinologists, since the disease may affect several organs and is associated with multiple comorbidities.