Thalassemia

Thalassemia is a group of a genetic disorder of hemoglobin synthesis characterized by a decreased synthesis of globin chain. It is a type of microcytic anemia which affects blood functioning. Two alpha and two beta chains of globin polypeptide combine with haem to form hemoglobin. If synthesis of globin is reduced it will lead to decreased hemoglobin (anemia). Anemia is a condition in which body does not have enough normal, healthy red blood cells due to the destruction of erythrocytes at the massive rate. It is inherited meaning that at least one of your parents must be a carrier of the diseases. If both of your parents are carriers of thalassemia, you have a greater chance of inheriting a more serious form of thalassemia.
Several types and subtypes of the thalassemia exist, and symptoms depend on the type of disorder.

Types of thalassemia

• In normal (homozygote) both polypeptide genes are normal and produce normal beta polypeptide chains in normal quantity.
• In heterozygote conditions, one gene is abnormal and fails to perform its function but the normal gene produces enough beta chain to maintain hemoglobin level about normal. Such condition is referred to as Beta-thalassemia minor. 
• In thalassemia conditions a patient's blood contains abnormal homozygote-beta chain, both genes are abnormal and do not produce beta polypeptide chain. Such condition is called Beta thalassemia major. 
• Decreased beta chain results in unbalanced polypeptide chain production. Beta chain production is impaired or stopped while alpha chain production is normal. Alpha chain will combine with any beta chain available while remaining alpha chains combine with gamma chains to form hemoglobin F ( Fetal hemoglobin). The free alpha chains precipitate within the red cells resulting in the damage of the cell membrane and making them susceptible to phagocytosis by the reticuloendothelial system.

Beta thalassemia

Some of the most common subtypes of the Beta thalassemia are:

• Silent carrier, which usually does not cause symptoms
• A beta thalassemia trait, which causes mild anemia
• Thalassemia major ( cooley's anemia) which causes severe anemia, stunted growth, and an abnormally large spleen (splenomegaly)

Beta thalassemia major

It is a subtype of Beta-thalassemia and much more diverse than the alpha-thalassemia syndromes due to the diversity of the mutations that produce the defects in the beta globin gene. Individuals who have beta thalassemia major are usually homozygous for one of the common mutations or heterozygous for one of the common mutations. Both lead to an absence of beta globin chain production.

Symptoms of Beta-thalassemia major

Children affected by the Beta thalassemia major have following common symptoms:

1. Growth retardation
2. Intermittent infection
3. Severe anemia
4. Bone marrow hyperplasia causing bossing of skull
5. Hepatosplenomegaly

Investigations

Investigations are involved:

1. Blood picture
2. Serum ferritin high serum iron binding capacity saturated
3. X-ray of cranium: Indicates hair on end look.
4. Hemoglobin electrophoresis: Indicates a boom in fetal hemoglobin (HbF) 

Treatment

Following are some of the effective treatments for the Beta-thalassemia major.

1. Splenectomy
2. Bone marrow transplantation
3. Blood transfusion every 4-6 weeks

Alpha thalassemia

Some of the most common subtypes of the alpha-thalassemia are:

• Silent carrier, which does not cause symptoms
• An alpha thalassemia trait that can cause mild anemia
• Alpha-Thalassemia major is the most severe type. A developing fetus with this type of thalassemia needs a blood transfusion while still in the womb to survive.
• Hb H disease, which causes mild to moderately severe anemia, and an enlarge spleen ( the organ that removes worn-out old red blood cells )

Alpha thalassemia

It is characterized by an inactivation of alpha globin genes, which results in a relative increase in nonfunctional beta globin or gamma globin tetramers and subsequent cell damage. There are four alpha genes. If one gene is deleted there is no clinical effect and if two alpha genes are deleted there is mild hypochromic anemia. If all four are deleted, the baby is stillborn ( hydrops fetalis ).

Symptoms of Alpha thalassemia

Patients with the more severe type of alpha thalassemia can have:

1. Slight to extremely pale skin, slight jaundice, a swollen or large abdomen
2. Nerve problems or paralysis
3. Exercise intolerance
4. Coronary heart murmur (atypical sounds inside the heart)
5. Enlarged organs
6. Frequent infections

Treatments

• Hydrops fetalis - none
• Hemoglobin H - as for thalassemia major
• Avoid iron therapy
• Folic acid if required