Delta-Beta Thalassemia - Causes, Clinical Signs, Diagnosis, and Treatment

Introduction:

Researchers have stated that delta-beta thalassemia is caused due to mutation affecting chromosome 11. The mutation associated with this disorder is deletion type, which involves the deletion of delta and beta genes on chromosome 11. As delta and beta genes get deleted, the gamma gene's production increases to compensate for the loss. Thus, resulting in an increase in HbF production. A total of nine mutations are noted, which results in delta-beta thalassemia. This variant of thalassemia is mainly noted in Mediterranean regions, including Italy, Greece, and turkey, and it is a rare finding in the Indian subcontinent.

What Is Delta-Beta Thalassemiasand How Is It Different From Other Thalassemias?

Thalassemia is a group of inherited hematological disorders (blood disorders) which is caused due to defects in the synthesis of the hemoglobin chains.

Broadly, thalassemia has been classified as

• Alpha Thalassemia: It is caused due to reduced or absence of the synthesis of the alpha globin chain.

• Beta-Thalassemia: It is caused due to reduced or lack of synthesis of the beta-globin chain.

Apart from these, there are six beta-thalassemia syndromes (a set of associated symptoms describing a particular condition), and gamma thalassemia is one of them.

So, the following are the thalassemia syndromes:

1. Beta thalassemia.

2. Delta-beta thalassemia.

3. Gamma thalassemia (γ-thalassemia).

4. Delta thalassemia.

5. Εγδβ- thalassemia.

6. HPFH syndrome.

So, it can be concluded that thalassemia is one of the forms of the syndromes associated with it, and they present almost similar features as another thalassemia.

How Does an Individual Get Affected by Thalassemia?

Hemoglobin is formed by the heme ring and the globin chain. The heme ring consists of iron, and the globin chain consists of two alpha and two beta chains. The composition of the globin chain determines the type of hemoglobin. At birth, fetal hemoglobin (gamma globin) accounts for 80 % of the hemoglobin, whereas the other 20 % of the hemoglobin is formed by alpha hemoglobin.

The transition of this gamma-globin to beta-globin begins even before the child's birth. In normal cases, fetal hemoglobin comprises two alpha and two gamma chains, whereas, in adults, the hemoglobin is made up of two alpha and two beta chains. But in individuals suffering from thalassemia, there is a reduction or absence of one of the globin chains, alpha globin chain or beta globin chain. Alpha-globin synthesis is controlled by genes present on chromosome 16, whereas genes on chromosome 11 control beta-globin synthesis. Mutations (alteration of the genetics sequences) in these genes lead to faulty globin chain synthesis, resulting in thalassemia-like conditions. Researchers have mapped around 200 mutations responsible for thalassemia.

Can a Child Get Thalassemia From Their Parents?

Thalassemia is an inherited genetic disorder with an autosomal recessive pattern of inheritance. This means that both the parents, the mother and the father of the individual affected by it, carry the defective genes, but the parents do not show the symptoms of the disease. Genetic mutations (structural changes in the genes) are associated with any type of thalassemia. There is a 25 % chance or probability that parents who are carriers of the thalassemia-causing defective gene will have children who will have the same. Genetic mapping in the prenatal stage can help doctors analyze the probability of the child suffering from thalassemia.

What Are the Signs and Symptoms Seen in Individuals Suffering From Delta-Beta Thalassemias?

The symptoms depend upon the form of thalassemia the patient is suffering from

• Thalassemia Major:

• Severe anemia.

• Pallor (paleness of the skin): It is a common finding noted in such individuals.

• Regional growth: The growth of individuals suffering from thalassemia is noted to be retarded or slowed down compared to individuals of the same age group.

• Splenomegaly: The enlargement of the spleen is also noted. Due to splenomegaly, individuals suffer from loss of appetite; they feel full even if they have no food.

• Frequent infections in the ear, nose, and throat.

• As there is an increased iron overload in such patients, disorders related to endocrine glands are very commonly noted, which include hypothyroidism (decreased functioning of thyroid glands, diabetes mellitus, and testicular and ovarian failure.

• Thalassemia Minor: Anemia symptoms are less severe than thalassemia major, and frequent blood transfusion is not required in such patients.

• Thalassemia Intermedia: This form depicts symptoms between major and minor types. It is comparatively less severe than thalassemia major.

What Are the Laboratory Tests Advised for Diagnosing Delta-Beta Thalassemias?

Following are a few laboratory tests that help the doctor diagnosing delta-beta thalassemia:

• Test for anemia which includes hemoglobin count and mean corpuscular volume (MCV).

• Peripheral blood smear in this test blood sample collected from the patient is spread on the glass slide, and a microscopic examination is done to analyze the shape and number of the red blood cells.

• Serum ferritin level is tested to get an idea regarding the stored iron levels.

• Hemoglobin electrophoresis is the process in which the hemoglobin is moved under the influence of the electric field, which helps determine the quality and physical properties of the hemoglobin.

• Genetic tests are the latest laboratory tests advised by the doctor. These tests are done to identify and analyze the genetic composition of the individuals. The defective genes are identified, and the cause of thalassemia and its type can also be determined.

What Are the Radiographic Findings Noted in Delta-Beta Thalassemias?

Radiographic findings mean the features seen in the X-ray reports (radiographs) of the individuals. Following are the few common radiographic findings noted in delta-beta thalassemia:

• Radiographic examination of long bones depicts thinning of the bone, and a decrease in bone density is also noted.

• Bone marrow cavities get narrowed in individuals suffering from delta-beta thalassemia.

• Sunray appearance is a common radiographic finding noted in such cases. The bone reactions in the outer surface of these bones result in such an appearance.

• Widening of the skull plates gives an appearance of hair on end.

• The maxillary sinus, one of the four paranasal sinuses, gets enlarged in such patients.

• Dental issues can also be noted, which include protruded upper jaw teeth and increased overbite.

• There is an increased probability of bone fractures in such disorders.

What Are the Treatment Protocols For Delta-Beta Thalassemia?

• Blood transfusions help compensate for the abnormal hemoglobin present in these individuals with normal hemoglobin.

• Iron chelation therapy is based on decreasing iron overload by removing excess iron.

• Splenectomy means surgical removal of the spleen.

• Bone marrow transplant focuses on correcting faulty hemoglobin production.

• Gene therapy is based on targeting the defective genes causing this disorder. They are still a topic of research.

Conclusion:

Thalassemia affects humans worldwide and is a significant concern for healthcare workers. Awareness programs and voluntary blood donation camps can help treat thalassemia patients better, improving the prognosis. Early diagnosis can help in enhancing the life expectancy of the individual. Moreover, advancements in the field of medical genetics are focusing on developing new treatment modalities.