Thalassemia

Thalassemia is a blood disorder affecting the haemoglobin genes and resulting in abnormal synthesis of haemoglobin. The decreased production of haemoglobin results in anaemia from an early age, and the patients require frequent blood transfusions to maintain normal haemoglobin levels.

Causes of Thalassemia

Haemoglobin (Hb) is a protein molecule present in the erythrocytes that carries oxygen. Each haemoglobin molecule consists of four subunits, two α-subunits and two β-subunits.

α-globin genes are located on Chromosome 16 (two genes: HBA1 and HBA2)
The β-globin gene is located on Chromosome 11 (single gene: HBB)

A deletion of key gene fragments or a mutation in these genes results in the erroneous synthesis of the subunits, thus producing a faulty haemoglobin molecule that cannot carry sufficient oxygen; as a result, anaemia begins in early childhood and lasts lifelong. Thalassemia follows an autosomal recessive mode of inheritance.

Types of Thalassemia

α-thalassemia:

The genes of the α-subunit of haemoglobin show a mutation or abnormality.

α depicts fully functional A1 or A2 alleles.

It depicts deletion of A1 or A2 alleles.

Condition	Functional alleles	Representation of the α-alleles	Anaemic Condition
Normal	4	(αα/αα)	Healthy
Silent Carrier	3	(αα/α-)	Healthy
Thalassemia trait	2	(αα/--) OR (α-/α-)	Mild
Hb H disease	1	(α-/--)	Intermediate
Hb B disease (Hb Bart’s hydrops fetalis)	0	(--/--)	Lethal

β-thalassemia:

The gene of the β-subunit of haemoglobin shows a mutation or abnormality.

The β+ allele depicts the mutation in the gene that results in a shorter chain of β-globin.

The β0 allele depicts the mutation which results in the absence of β-globin.

Condition	Functional alleles	Representation of the β-alleles	Anaemic Condition
Normal	2	(β/β)	Healthy
Thalassemia minor	1	(β/β+) OR (β/β0)	Mild
Thalassemia intermedia	0	(β0/β+) OR (β+/β+)	Intermediate
β-thalassemia	0	(β0/β0)	Severe but not always lethal with treatment

Symptoms of Thalassemia

Carriers (thalassemia minor) are usually asymptomatic but may show mild anaemia or microcytosis detectable on blood tests. Missing more than two alleles (α-thalassemia) or missing more than one functional allele (β-thalassemia) can result in the following symptoms.

Anaemia

Anaemia would certainly develop in the thalassemia patients, which might be life-threatening in some severe cases. Anaemia occurs due to low levels of haemoglobin protein and can cause-

Shortness of breath
General tiredness
Palpitations and irregular heartbeats
Jaundice

Iron build-up in the body

Repeated blood transfusions might increase the risk of excess iron accumulation in the body, which can affect in the following ways-

Cardiomyopathy
Cirrhosis of the liver
Low levels of testosterone and oestrogen, in both males and females.
Delayed puberty.
Diabetes.
Decreased function of thyroid and parathyroid glands.

Other problems

Gallstones may develop, which can cause inflammation of the gallbladder, accompanied by stomachache.
Enlarged forehead or cheeks due to abnormal bone growth.
Osteoporosis.
Dark or tea-colored pee.
Swollen belly.
Babies with β-thalassemia may be especially fussy and get frequent infections.

Treatments for Thalassemia

Mild thalassemia (trait/minor) usually needs no treatment but may require monitoring and folic acid supplementation. But acute thalassemia requires the following treatments-

Blood transfusion to deal with anaemia.
Chelation therapy is also required alongside blood transfusion to reduce the risk of excess iron accumulation.
Bone marrow transplant (BMT)
Supplements and Medications, but iron-containing supplements are not suggested.

Prevention of Thalassemia

Lifestyle measures cannot cure thalassemia, but the condition can be prevented at the population level.
Before conceiving, a couple should consult a genetic counsellor to detect the probability of the offspring carrying the missing genes or exhibiting the disease.
The disease can also be detected through some prenatal tests.

Frequently Asked Questions (FAQs)

Q1. What is the genetic cause of thalassemia?

A. Thalassemia occurs due to mutations or deletions in the α-globin genes (Chromosome 16) or the β-globin gene (Chromosome 11), leading to reduced or absent synthesis of globin chains required for haemoglobin formation.

Q2. Why do thalassemia patients need frequent blood transfusions?

A. In severe forms (like β-thalassemia major), haemoglobin production is insufficient. Blood transfusions are given regularly to maintain normal haemoglobin levels and prevent severe anaemia.