Thalassemia

Thalassemia is a group of inherited blood diseases. It is caused by abnormal production of hemoglobin, which is a protein found in red blood cells that is responsible for transporting oxygen. Hemoglobin is composed of two chains, alpha and beta globin, and there are two main types of thalassemia depending on the type of globin that is affected:

Alpha thalassemia:

Individuals affected by this type of thalassemia do not produce enough alpha globin. There are two genes (and therefore four alleles) that control the production of this type of globin. Depending on the number of abnormal or missing alleles, several types of alpha thalassemia can be found, which vary in their symptoms and degree of severity.

Individuals with the mildest form are known as silent carriers. In this case, only one alpha globin allele is missing, and affected individuals can transmit the disease to their offspring but do not develop symptoms. When two alleles of alpha globin are missing, it is called alpha thalassemia minor, and patients may suffer from mild anemias, although they may also not have any symptoms at all. Nevertheless, there still exists a chance that they transmit the disease to their offspring.

Hemoglobin H disease is what we call when three alleles of alpha globin are missing. In this case, affected individuals have abnormalities in red blood cells that result in mild to moderate anemias, although overall they can lead a relatively normal life. Anemia may worsen if patients have viral infections or use certain medications. Individuals with this disease may suffer from complications such as an enlarged spleen, gallstones, and recurrent infections. They usually visit the doctor regularly, and the disease is diagnosed and the complications derived from it are treated in a timely manner. In some cases, patients may require blood transfusions.

Finally, the most severe form is known as alpha thalassemia major, or Bart’s disease, and in this case, there are no alpha globin alleles present at all. Affected fetuses may suffer from severe anemia, heart failure, and fluid accumulation. In general, these cases usually result in stillbirth or death within a few hours of birth, and there is no effective treatment.

Beta thalassemia:

Individuals affected by this type of thalassemia do not produce enough beta globin. The production of this protein is controlled by one gene, so each person has two alleles. Symptoms and severity vary depending on whether one or both alleles are mutated and also on the severity of each particular mutation.

It is called beta thalassemia minor when a mutation occurs on one of beta globin’s alleles. Most patients have no symptoms, although they may have mild anemia and pass the defective gene to their offspring.

Beta thalassemia intermedia is caused by mutations on both beta globin alleles, but these mutations are not as serious as those that cause thalassemia major. Children with this disorder have symptoms similar to those seen in hemoglobin H disease: mild to moderate anemia, enlarged spleen, etc. Regular blood transfusions are often required for symptom control.

The most severe form of this type of thalassemia is beta thalassemia major, or Cooley’s anemia, which is caused by the presence of severe mutations on both beta globin alleles. Most children affected by this disease appear healthy at birth, but during the first months of life they begin to develop symptoms such as pallor, delayed growth, or jaundice (yellowish skin and eyes). If left untreated, they can develop other complications, such as enlarged spleen and liver, bone weakness, frequent infections, and heart failure caused by the accumulation of iron in the heart. These patients require regular blood transfusions since they develop first symptoms.

In recent years, it has been possible to cure some patients with this disease through bone marrow transplantation, although this is not always possible because a donor match is not always easily found, not to mention the risk involved with the procedure itself.

In alpha thalassemia, the HBA1 and HBA2 genes, the genes involved in the production of a hemoglobin subunit called alpha globin, are affected. Each person has two copies of each of the genes in each cell, and the different types of alpha thalassemia develop according to the number of missing alleles, leading to different symptoms and severity.

Beta thalassemia is caused by mutations in the HBB gene, which encodes the beta subunit of hemoglobin. Depending on the severity of the mutation or the number of missing copies of the gene, it will lead to the various types of beta thalassemia with different symptoms.

Thalassemia is one of the most common genetic disorders worldwide; about 100,000 children are born affected by different forms of this disease every year. Approximately 5% of the world’s population carries a mutated hemoglobin gene. Thalassemia occurs most often in Southeast and Central Asia, in the Mediterranean countries, and in North Africa.

This disease follows an autosomal recessive inheritance pattern of inheritance, meaning that two mutations are necessary, one from each parent, for the disease to develop. It can be transmitted by both men and women. Therefore, when both parents are carriers of altered gene alleles, all children are at risk of inheriting one or more of them and developing some type of this disease.

Alheta – Spanish Association for the Fight against Haemoglobinopathies and Thalassemia

TIF – Thalassaemia Internacional Federation

CAF – Cooley’s Anemia Foundation