Thalassemia

What is Thalassemia?

• Thalassemia are inherited blood disorder caused by abnormal hemoglobin. It occurs when there is a defect in a gene that helps control production of hemoglobin. Thalassemia is a type of Hemoglobinopathies and are the most common single gene disorder in the world population
• Affected individual (Thal Major) cannot make enough Red Blood Cells and needs to be supplemented with RBC transfusions every 2-3 weeks to stay healthy and to survive. Without treatment, affected individual have severe failure to thrive and shortened life expectancy.

• There are different types β-chain structural variant of human hemoglobin ( S, C, D, & E) .Other most common type of Hemoglobinopathies includes HbE and HbS.
• These disorders can be inherited together, if both the partners are carriers/affected due to different Hemoglobinopathies.Some, co inherited variants like β-HbS is responsible for variable range of clinical features from normal to affected; β-HbC only cause mild anemia where as β –HbE present like Thal major and require frequent transfusion.

Is it common in India?

• Every year approximately 100,000 children with Thalassemia Major are born world over, of which 10,000 are born in India
•  It is estimated that there are about 65,000-67,000 β-thalassemia patients in our country with around 9,000-10,000 cases being added every year
•  Over 1, 00,000 patients across the country die before they turn 20 due to lack of access to treatment
• India is the thalassemia capital of the world with 40 million carriers
• The carrier rate for β-thalassemia is 3.3 % in India and several ethnic groups have a much higher prevalence (4–17%)

How can we know our carrier status?  

• All Hemoglobinopathies can be identified by CBC, Peripheral smear along with Hb electrophoresis/HPLC.
• Borderline/normal HbA₂ levels (3.0–3.9%) often lead to a diagnostic dilemma 
• In India, borderline HbA₂ with near normal or reduced red cell indices in β thalassemia heterozygotes is most often due to the cap site +1 (A > C) mutation and the poly A (T > C) mutation but there are several β thalassemia heterozygotes with other severe mutations who also show borderline or normal HbA₂ levels
• These unusual heterozygotes would be missed in screening programs but utmost care should be taken and β genotyping should be done in a couple when one of the partners is a classical

Is there any treatment?  

At present, life expectancy varies between 25-55 years depending on compliance with medical treatment. Despite increased life expectancy, it possesses many psychological challenges.

Bone marrow transplantation is an available treatment option to increase the thalassemia survival rate

    

How do we get thalassemia?  

• Thalassemia can be inherited with or without family history of disease 
• It affects both the sexes equally
• All of us have 2 copies of gene which produce hemoglobin in our body. We inherit one copy of each gene from our parents.
• Affected people (Thal major) have no healthy copies of the gene and thus, hemoglobin production is less. 
• Patient affected with thalassemia will always have carrier parents (Thal minor; carrying one faulty and one healthy

• copy of gene). Since, they have one healthy copy of the gene, there will be production of hemoglobin, hence they have mild anemia and lead a normal life. 
• This type of gene segregation is known as Autosomal Recessive inheritance pattern; where in each pregnancy there will be a 25% chance of having a child with thalassemia.
• More than 200 mutations are known to be associated with Thalassemia. Among which five common mutations IVS 1-5 G → C, IVS 1 -1 G → T, Codon 41/42 (- TCTT), Codon 8/9 and the 619bp deletion account for over 90% of the mutations in Indian ß-thalassemia patients.

How can we prevent Thalassemia? 

• Once an individual is found to be a carrier/affected, genetic testing is important to identify the gene defect. 
•  Prenatal diagnosis, tests during pregnancy can diagnose Thalassemia in the baby. In this, chorionic villus sampling (CVS), a small sample of the placenta is removed from the womb and tested for the haemophilia gene, usually during weeks 12 to 14 of pregnancy. As it’s invasive procedure, there’s a small risk of miscarriage.
• Thalassemia can also be prevented by Pre-Implantation Genetic Test-M (PGT-M). 

Geographic and community wise distribution of β-Thalassemia 

• Certain communities in India, such as Sindhis and Punjabis from Northern India, Bhanushali’s, Kutchis, Lohana’s from Gujarat, Mahar’s, Neobuddhist’s, Koli’s and Agri’s from Maharashtra, & Gowda’s and Lingayat’s from Karnataka etc. have a higher carrier rate
• HbE is prevalent in the north-eastern and eastern region with the frequencies of HbE carriers range from 3 to over 50%
•  HbS is prevalent in Odisha and some city of Maharashtra like Nagpur.

Dr. Mitesh Shetty

Head of Department & Consultant, Medical Genetics

Manipal Hospitals, Bangalore