Thalassemia

Thalassemia

Thalassemia is an inherited blood disorder that affects your body’s ability to produce haemoglobin. Individuals with thalassemia present with severe anemia and enlargement of liver and spleen needing medical treatment in the first two years of life. It is a common genetic disorder and in India about 10,000 -20,000 children are born every year with thalassemia. There are two types of thalassemia, alpha and beta thalassemia. Thalassemia is a genetic disorder caused due to changes in HBB, HBA1 or HBA2 gene.

Symptoms

Most infants or children less than 2 years of age present with:

• Anemia
• Pale skin
• Acting cranky or upset
• Not growing as much as expected
• Swelling of the belly
• Sallow complexion
• Facial bone or skull being wider than usual
• Dark urine
• Weakness
• Fatigue

Symptoms of thalassemia develop anytime from birth to the first two years of life. Some children having beta thalassemia or alpha thalassemia may show signs after 6 months of age due to fetal hemoglobin present in blood which later get replaced by normal haemoglobin whereas, some individuals may present with a milder form of anemia at a later age.

Diagnosis 

Diagnosis of thalassemia is established by

• Complete Blood Count (CBC) and Peripheral blood smear: Checking haemoglobin levels and characteristic findings of red blood cells.
• Genetic testing: DNA analysis for checking changes in genes that can cause abnormal haemoglobin production

Treatment

Mild forms of thalassemia may not require treatment but severe form require blood transfusions and other forms of medical treatment.  Thalassemia treatment is done according to the type and seriousness of disorder. Some thalassemia treatments include:

• Blood transfusion
• Bone marrow transplant
• Medication & supplements
• Surgery to remove gallbladder or spleen

Complications

If thalassemia becomes severe, it can lead to organ failure or can be fatal. Individuals with mild to severe thalassemia may face complications such as:

• Iron Overload: Excess of iron in body can lead to heart and liver damage due to repetitive transfusions and can be rectified by chelation therapy.
• Bone Deformities: Bones become thin & brittle due to expansion of bone marrow and can lead to abnormal face structure.
• Slow Growth: Growth of the body gets slow, and adolescents may present with delay in puberty.
• Enlarged Spleen: Spleen may enlarge due to damaged red blood cells. Doctors may recommend removing spleen if it grows too big.
• Heart Problems: Severe thalassemia can lead to congestive cardiac failure and arrhythmia.
• Pregnancy complications: Genetic counselling is essential for couples with a personal or family history of thalassemia to understand the risk passing on the genetic changes. Preconception and prenatal genetic counselling can help couples plan for reducing risk of passing on the genetic change and having a safe pregnancy. Individuals with thalassemia have a high chance of having cardiomyopathy and diabetes during pregnancy.

Genetics of thalassemia

Each haemoglobin molecule contains two chains of Alpha chains and beta globin. Genes are letters or codes that provides instructions to our body for every function. For every gene, we receive two copies, one from each parent. Changes in this code can affect the function of alpha or beta globin in turn producing a defective haemoglobin molecule. Thalassemia is an autosomal recessive condition, an individual who is affected inherits two genetic changes, one from each parent. Parents who have one genetic change but has a second normal working copy of the gene is known as a carrier and is usually unaffected or mildly affected with anaemia.

• Alpha thalassemia: Normally each individual has four alpha-globin (α-globin) genes, i.e., HBA1 and HBA2, inactivation of HBA1 or HBA2 reduces production of α-globin chains. The severity relies on the inheritance of gene mutation from parents. If you inherit:
• One-muted gene: No symptoms and signs but the individual is a carrier.
• Two-muted gene: Symptoms will be moderate
• Three-muted gene: Symptoms varies from moderate to severe.
• Four-muted gene: It is rare and mostly causes stillbirth. But in some rare cases, child is treated by transfusion or by bone marrow transplant.

In beta thalassemia: we receive two copies of the HBB gene from each parent. Beta thalassemia is caused by inheritance of two genetic changes in the HBB gene, one from each parent. However, the severity of the disease depends upon the effect of genetic change on the production of the beta globin.

• Gene change that causes complete loss of beta globin can cause moderate to severe and is called thalassemia major or Cooley anaemia.
• Gene change that causes partial loss of beta globin can cause mild to moderate symptoms called thalassemia minor

Genetic counselling, Preconception & Prenatal testing

Genetic counselling is a process of providing individuals and families with information regaring the disease, management, treatment, understanding the risk of inheritance and options for prevention or early detection. Genetic counsellors are specialised health care who have expertise in medical genetics as well as counselling who can help families in managing and adjusting to the genetic disease. Couples with personal or family history of thalassemia are recommended to meet with a genetic counsellor or geneticist to understand the risk of inheritance and risks to other family members. Couples who are planning for a family can discuss genetic testing options. Couples who are pregnant can opt for genetic testing during the pregnancy to understand if the fetus is a affected.  

• Chorionic villus sampling (CVS): Around 11^th week of pregnancy, a piece of placenta is tested for defected gene.
• Amniocentesis: Amniotic fluid around the foetus is tested around 16^th week of pregnancy.

In case of couple opting for assisted reproductive technology such as in vitro fertilization (IVF), screening of embryo for genetic defects can be done before implantation.

It is recommended to undergo thalassemia screening to all women planning for pregnancy regardless of personal or family history of thalassemia. Genetic counsellors are experts in addressing social, ethical or legal challenges. A counselling session can be helpful to understand the risks, benefits and limitations of genetic testing.

Inputs by Ms. Neeraja Malleda, Genetic Counselor, Apollo Hospitals Navi Mumbai