Gamma-Thalassemia: A Brief Review

Introduction

γ-thalassemia is the rarest type of thalassemia. It is associated with the crossover between globin genes resulting in the formation of a gamma hybrid gene. The gamma hybrid gene is formed due to the deletion of 3' and 5' DNA (deoxyribonucleic acid) sequences from the G gamma gene and A gamma gene, respectively. The frequency of occurrence of γ-thalassemia is very low and is mainly found in developing countries like India, China, and Africa. DNA analysis of the newborn leads to the diagnosis of γ-thalassemia.

What Is γ-Thalassemia and How Is It Different From Other Thalassemia?

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

Broadly thalassemia has been classified as:

1. Alpha thalassemia.

2. Beta-thalassemia.

Alpha thalassemia is caused due to reduced or absence of the synthesis of the alpha globin chain. In contrast, beta-thalassemia is caused due to reduced or lack of synthesis of the beta-globin chain. Apart from these are six beta-thalassemia syndromes (a set of associated symptoms describing a particular condition), and gamma thalassemia is one.

The following are the thalassemia syndromes:

1. Beta thalassemia.

2. Delta beta thalassemia.

3. Gamma thalassemia (γ-thalassemia).

4. Delta thalassemia.

5. Εγδβ- thalassemias.

6. HPFH (hereditary persistence of fetal hemoglobin) syndrome.

How Does an Individual Get Affected by Thalassemia?

The heme ring and the globin chain form the hemoglobin. 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 percent of the hemoglobin, whereas the other 20 percent 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 comprises two alpha and two beta chains. However, 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 beta-globin synthesis is controlled by genes present on chromosome 11. Mutations (alteration of the genetics sequences) in these genes lead to faulty globin chain synthesis, resulting in thalassemia-like conditions. Researchers have mapped around two hundred 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 thalassemia, carry the defective genes, but the parents do not show the disease symptoms. Genetic mutations (structural changes in the genes) are associated with any type of thalassemia. There is a 25 percent chance or probability that parents who are carriers of the thalassemia-causing defective gene will have children with thalassemia. Genetic mapping in the prenatal stage can help doctors analyze the likelihood of the child suffering from thalassemia.

What Are the Signs and Symptoms Seen in Individuals Suffering From γ -Thalassemia?

Following are a few standard features noted in individuals suffering from γ-thalassemia:

• 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, that is, 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.

What Are the Laboratory Tests Advised for Diagnosing γ -Thalassemia?

Following are a few laboratory tests that help the doctor diagnosing γ -Thalassemias:

• Test for anemia, which includes hemoglobin count and mean corpuscular volume.

• Peripheral blood smear, in this test blood sample collected from the patient is spread on the glass slide and examined under a microscope to look for the shape and number of the red blood cells carrying the hemoglobin.

• Serum ferritin level is tested to understand 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 γ -Thalassemia?

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

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

• Bone marrow cavities look narrowed in individuals suffering from γ-thalassemia.

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

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

• The maxillary sinus, which is 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 γ-Thalassemia?

• Blood transfusions help compensate for the abnormal hemoglobin present in these individuals to get 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 faulty genes causing this disorder. Gene therapies 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 medical genetics are focusing on developing new treatment modalities.