Posted On May 07, 2020
HOD & Consultant - Medical Genetics
Manipal Hospitals - Old Airport Road - Bengaluru
5 min read
5 min read
Thalassemia is an inherited blood disorder caused by abnormal haemoglobin. It occurs when there is a defect in a gene that helps control the production of haemoglobin. Thalassemia is a type of Hemoglobinopathy and is 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, the affected individual has severe failure to thrive and shortened life expectancy.
There are different types of β-chain structural variants of human haemoglobin ( S, C, D, & E). Other most common types of Hemoglobinopathies include 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 are responsible for a variable range of clinical features from normal to affected; β-HbC only causes mild anaemia whereas β –HbE present like Thal major and require frequent transfusion.
Every year approximately 100,000 children are born with Thalassemia Major in the world, out 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 and every year there are around 9,000-10,000 new cases added.
Over 1, 00,000 patients in India die before they turn 20 due to lack of access to treatment.
India is the thalassemia capital of the world with 40 million carriers. Visit the Genetics hospital in Bangalore to know more about Thalassemia.
The carrier rate for β-thalassemia is 3.3 % in India and several ethnic groups have a much higher prevalence (4–17%).
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 carrier of β thalassemia.
At present, life expectancy varies between 25-55 years depending on compliance with medical treatment. Despite increased life expectancy, it possesses many psychological challenges. Consult with the genetics doctor in Bangalore for the treatment that suits you.
Bone marrow transplantation is an available treatment option to increase the thalassemia survival rate.
Thalassemia can be inherited with or without a family history of the disease.
It affects both the sexes equally.
All of us have 2 copies of genes that 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.
The patient affected with thalassemia will always have carrier parents (Thal minor; carrying one faulty and one healthy copy of the gene). Since they have one healthy copy of the gene, there will be a production of hemoglobin, hence they have mild anemia and lead a normal life.
This type of gene segregation is known as the Autosomal Recessive inheritance pattern; wherein 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.
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 hemophilia gene, usually during weeks 12 to 14 of pregnancy. As it’s an 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 regions with the frequencies of HbE carriers ranging from 3 to over 50%.
HbS is prevalent in Odisha and some cities of Maharashtra like Nagpur.
Head of Department & Consultant, Medical Genetics