What is Thalassemia?
Thalassemia is a genetic disorder. Our body produces a protein called haemoglobin which is responsible for transporting oxygen to various parts of our body. In this disease, the body produces abnormal red blood cells. This results in various other complications in our body.
How is thalassemia caused?
Thalassemia is an autosomal recessive disorder. This means that only the non-expressed gene carries the disorder. So, for the disorder to be expressed, both the parents must have the gene.
There are 4 protein chains in an adult haemoglobin protein. They are two alpha and two beta chains. In patients affected by thalassemia, there are defects in these protein chains. Based on the location of the defect, we can classify thalassemia into two types: alpha and beta thalassemia.
When there is a defect in the alpha chain, it leads to lowered levels of alpha globin. This results in relatively higher levels of beta globin (and delta globin levels in infants). The increased beta side chains form unstable tetramers and this leads to reduced oxygen dissociation curve.
When there are mutations in the HBB gene on chromosome 11, it causes beta thalassemia. It is also inherited in an autosomal recessive fashion. There are three subtypes:
- Beta thalassemia major
- Beta thalassemia intermedia
- Beta thalassemia minor
Who are at a risk?
Thalassemia is governed by a set of risk factors which increase the probability of their occurrence.
- Family history: since thalassemia is and autosomal recessive disorder, the risk factor is increased in those patients with a history of thalassemia in their family line.
- Ancestry: thalassemia is common in people of Italy, Greece, Middle Eastern, South Asian, and African ancestry. Alpha thalassemia is common in people of Southern Asia, Chinese and Filipino descent.
What are the signs and symptoms of thalassemia?
The sign and symptoms of thalassemia are:
- Increased iron content: this is one of the most common and dangerous symptoms of thalassemia. It could either be caused due to the disease itself or due to frequent blood transfusions. Iron accumulation can cause damage to vital parts like the liver, kidneys, heart and endocrine system. Without adequate iron chelation therapy, almost all thalassemia patients end up with fatal levels of iron deposits.
- Bone deformities: thalassemia causes expansion of bone marrow. as a result, bone also expands. This leads to abnormal deformations of the bones. It is especially noticeable in the face and skull. The rapid expansion also leads to thinning of the bone and eventually fracture of the brittle bone.
- Infections: people with thalassemia have an increased risk of infection. This is especially true if the spleen is removed.
- Enlarged spleen: one of the main functions of spleen is to destroy defective cells. So, when there is an increased production of defective haemoglobin cells, the removal of these cells is by the spleen. The functional overload leads to an enlarged spleen. This will only worsen the condition of anaemia, leading to a vicious cycle.
- Delayed growth rates: due to the reduced haemoglobin levels, there is a delay in growth of children. Puberty may also be delayed.
- Heart problems: congestive heart failures, arrhythmias may also develop as a complication of thalassemia.
- Paleness: due to anaemia
- Coloured urine
TYPES OF THALASSEMIA:
What is coolie’s anaemia?
Thalassemia major is also known as Coolie’s anaemia.
It is the most severe form of thalassemia. It occurs due to a deficiency in beta thalassemia. The symptoms usually present before two years of age. This severe form of anaemia can even be life-threatening. They symptoms are:
- Frequent infections
- Enlarged organs
- Bone deformities
- Poor appetite
- A general failure to thrive
It can occur either due to alpha or beta deficiency. the symptoms are minor anaemia or usually no symptoms at all.
It is difficult to diagnose thalassemia minor as it rarely shows. It is advisable to check for family history for diagnosis.
This occurs when the body cannot make alpha globin genes. There are two main types of alpha thalassemia which are serious:
- Haemoglobin H disease
- Hydrops foetalis
Haemoglobin H disease:
- It occurs when there is deficiency of three alpha globin genes.
- The patient experiences bony deformations
- There is overgrowth of cheeks, head, jaws
- Patient presents with jaundice, enlarged spleen and malnourishment
- All four alpha globin genes are missing
- It affects the individual even before birth
- The children are usually stillborn babies.
Thalassemia and pregnancy:
Women with thalassemia often have pregnancy issues. Since this disorder affects fertility. Careful monitoring of the patient is kept so as to ensure healthy conception. The mother’s iron levels are also kept in check. Pregnancy carries the following risk factors:
- Increased risk of infections
- Low bone densities
- Gestational diabetes
- Increased blood transfusions
- Heart problems.
What are the complications of thalassemia?
- Slow growth and development
- Bone deformities: the expansion of the bone marrow leads to expansion of the bones, especially of the skull and face. This further leads to thinning of the bones, making them more susceptible to fracture.
- Increased rate of infection: increased frequency of transfusions and removal of spleen, all play a role in making the patient more susceptible to infections.
- Iron overload: this is due to the continuous blood transfusions. This may further lead to scarring of liver (fibrosis), hepatitis, and cirrhosis of liver. The increased iron content may lead to delayed puberty and growth. Later, it may increase the risk of diabetes and hyper or hypothyroidism. Abnormal iron levels also cause increased risk of arrhythmias and congestive heart failure.
- Splenomegaly: the spleen is the destruction centre for abnormal red blood cells. Due to the increased levels of destruction, the spleen gets enlarged and may start destroying healthy red blood cells also. Sometimes the patient may need a splenectomy (removal of the spleen).
- Heart problems: arrhythmias and abnormal heart rates, heart beats and congestive cardiac failure due to increased iron content is seen.
How do we detect thalassemia?
The diagnosis of thalassemia partly lies in the careful recording of the patient’s medical history. This includes the patient’s parental history, ethnicity, family history etc.
The symptoms of the disease usually show up by the age of two.
- COMPLETE BLOOD COUNT TEST: a CBCT is the most commonly performed test. The size and shape of the cells, number of cells can be studied in this test. If any abnormal sizes and shapes are present, it further helps to group the type of thalassemia.
- RETICULOCYTE COUNT: reticulocytes are immature form of red blood cells which develop into mature blood cells. At any given point, about 1-2% of the red blood cells are reticulocytes in a healthy individual.
- IRON CONTENT: this not only helps to determine the cause of anaemia, but also to keep a check on the iron levels in the body, which is seen to be increased in case of frequent blood transfusions. It is to be noted that anaemia in thalassemia is not caused due to iron deficiency.
- DNA analysis: this test is done in order to determine the cause of thalassemia and also identify the type of thalassemia. The fault in the protein chains can be detected.
- PRENATAL TESTING: This test is for foetal analysis and diagnosis. For parents who are either carriers or are affected with thalassemia and feel like their foetus may also be affected by the disease, they can undergo early diagnosis. There are two methods of determining the foetal condition for thalassemia:
- Chorionic villus sampling: this test is usually performed around the 11th week of pregnancy. A small portion of the placenta is taken for test and the foetal health is determined.
- Amniocentesis: this test is done during the 16th week. Some amount of amniotic fluid is taken and sent for testing if the foetus will have thalassemia.
How is thalassemia treated/managed?
Thalassemia is managed in different ways based on the severity of the disease. In mild cases, occasional blood transfusions are sufficient to keep the symptoms at bay. In case of moderate to severe cases, the patient has to undergo frequent blood transfusions, chelation therapy, bone marrow transplantation and sometimes splenectomy.
BLOOD TRANSFUSION: blood transfusions are replenishing the body’s blood cell levels when there is a shortage in the individual. Those patients who have mild thalassemia may require only one or two transfusions in a year. But those with severe thalassemia will require over eight to ten transfusions in a year, and even more during times of stress, injury and illness.
BONE MARROW TRANSPLANT: Bone marrow is a spongy tissue present within the bone that helps in forming blood cells and release it into the blood stream. When this is defective, a bone marrow transplant can be done. The bone marrow transplanted is done once a suitable donor is found or if the placenta is harvested earlier. The patient has to be on immunosuppressants so that the transplant is not rejected by the body.
CHELATION THERAPY: the frequent transfusions increase the amount of iron deposited in the body and tissues. The substances that are used for the therapy chemically bonds to the iron and other heavy metals, thus eliminating them from the body. It is a necessity to carry out chelation therapy in order to remove fatal quantities of iron.
SPLENECTOMY: if the spleen seems to be enlarged and inflamed to a point which is irreversible, the whole organ is removed.
General care for thalassemia patients:
- Do not miss any transfusion appointments or chelation therapy on the scheduled days.
- Follow healthy diet to maintain a good health
- Exercise regularly
- Foods like spinach, or iron-rich cereals should be avoided as they are rich in iron.
- Keep up to date with vaccinations to avoid infections.