Thalassemia – Is there a potential cure?

Thalassemia is one of the most common genetic diseases worldwide. It is estimated that around 60,000 individuals are born it with every year.

What it is actually?

They are a group of autosomal recessive inherited conditions where there is decreased or absence of synthesis of one of the two polypeptide chains (α or β) that form the normal adult human hemoglobin molecule (hemoglobin A, α2/β2), which results in reduced hemoglobin in red cells leading toanemia.

Thalassemia = thalassa (sea) and haima (blood)

Thalassemia Syndromes are named according to the globin chain affected.

β globin gene defects may give rise to β thalassemia, and α globin gene defect may cause α thalassemia.

How can thalassemia be diagnosed?

The Symptoms of hemolyticanemia appear first which includes paleness, hepatosplenomegaly—directly from birth in α thalassemia. While in β thalassemia these symptoms appears after many months of birth with the disease.

Investigatory Workup:

1.  Laboratory investigations reveals classically microcytic, hypochromic red blood cells (mean corpuscularvolume <70 fL), not responding to iron supplementation.

2.  Second line testing consists of separation and measurement ofthe hemoglobin fractions with high performance liquidchromatography (HPLC) or capillary electrophoresis.

3.  Third line testing at DNA level by standard Gap-PCRtechnologies or direct DNA sequencing.

Can thalassemia be prevented?

Prevention of thalassemia is based on public awareness of thedisease, detection of carriers, genetic counseling, and prenataltesting.

Carriers of α thalassemia should be offered counseling to estimate the risk of hydropsfetalis.

Testing and counseling should alsobe offered to all first degree relatives of a patient diagnosedwith thalassemia.


Asymptomatic carriers

Carriers require no specific treatment. However, they should be evaluated for iron deficiency, and Iron supplementation should begiven only after confirmation of iron deficiency


Patients with thalassemiaintermedia or hemoglobin H disease are monitored for progression of complications which can result from chronic hemolyticanemia.

Symptoms usuallydevelop when the hemoglobin level is sustained at below 7.0g/dL.

Blood transfusion may be required duringperiods of rapid growth, infection-associated aplastic crisis and pregnancy.

Indications for regular transfusion include growthimpairment and skeletal deformities.Ifhypersplenism develops,splenectomy is indicated.

Thalassemia major

This is the most severe form of disease and requires intensive management with regular bloodtransfusions to maintain a hemoglobin level> 9.5 mg/dL

Due to regular blood transfusion, these patients develop iron over load, so iron chelation is required regularly.

Excessive Blood Transfusion- Is it a problem?

Hypertransfusion decreases autogenous, ineffectiveerythropoiesis and haemolyticanaemia but the patient has to face the consequences of iron overload because each unit ofred blood cells adds 200 mg of iron, which can only be slowlyremoved from the body. The complications of iron overload arecardiomyopathy and liver cirrhosis and effects endocrine organs causing growth impairment, delayed or absent puberty,infertility, and diabetes mellitus.

The risk of transmission ofHIV, hepatitis B, and hepatitis C is always there.

How should iron overload be preventedand treated?

Experts recommend that iron overload be treated when serumferritin levels exceed 1000 μg/L, which will occur after 10 to20 red cell transfusions.

Oral or parenteral chelation therapy remains the mainstay to prevent iron overload.

Alternative therapeutic options

Splenectomy can be considered if hypersplenism causes amarked increase in transfusion requirements. In general, itshould be delayed for as long as possible, in order to prevent life threatening infections, pulmonary hypertension andthrombo-embolic complications.

Hydroxyurea, a cytotoxic drug has also shown some benefits.

Is there a potential cure?The most common question that comes to our mind.

The only potential cure for β thalassaemia is haematopoieticstem cell transplantation.

The success of stem cell transplantation depends on the amountof erythrocyte transfusions received and the severity of ironoverload.

Thepotential for success is furthermore determined by HLAmatching between the donor stem cells and patient HLA. Thepreferred source of donor stem cells is an HLA identical familymember.

Hematopoietic stem cell transplantation has shown in studies overall survival of 90% and diseasefree survival of 86% for a mean follow-up period of 15 years.

The younger the patient is at time of stem cell transplantation,the better the outcome.