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Thalassemia is a genetic
blood related disorder due to absent or reduced production of hemoglobin,
a protein responsible for carrying oxygen to the tissues.
Each red blood cell may
contain between 240 and 300 million molecules of hemoglobin.
A hemoglobin molecule has
two sub-units commonly referred to as alpha and beta.
Both sub-units are necessary
to bind oxygen and deliver it to cells and tissues in the body.
The alpha globin gene cluster
controls the production of alpha chains, and similarly the beta globin
gene cluster produces beta chains.
A lack of a particular subunit
determines the type of the resulting thalassemia (alpha or beta).
Thalassemia is derived from
the Greek word 'thalassa' meaning 'the sea' because the condition was first
described in populations living near the Mediterranean Sea.
However, it is now very
well known that thalassemia is the most common inherited single-gene disorder
in the world with the highest prevalence in areas where malaria was or
still is endemic (Mediterranean Basin, Australasia, the Americas and Africa).
In many parts of the world,
thalassemia still represents a major public health concern.
In beta-thalassemia, the
clinical presentation occurs from six to 24 months of age.
The severity of the damage
depends on the type of the gene mutation.
Some mutations (beta-zero)
prevent any formation of beta chains; others (beta-plus) allow some beta
chain formation to occur.
In the severe form of the
disease, the bone marrow expands as it attempts to keep pace with the perceived
need for new red blood cells, setting the stage for moderate-to-severe
skeletal deformities and pain.
If left untreated, affected
infants fail to thrive and become progressively pale.
Feeding problems, diarrhea,
irritability, recurrent bouts of fever, leg ulcers, osteoporosis, thrombotic
complications, and progressive distention of the abdomen caused by liver
and spleen enlargement may occur.
People with Mediterranean
(including North African), Middle Eastern, or Southeast Asian ancestry
are at higher risk of being carriers of beta-thalassemia than are other
Beta-thalassemia is a recessively
inherited genetic disorder that, in most cases, requires two defective
beta-globin genes to trigger the disease.
If only one mutant copy
of the beta-globin gene is inherited, no symptoms may appear; this condition
is called beta-thalassemia minor or beta-thalassemia trait. Hence, a positive
family history of beta-thalassemia is an important indication for an individual
to seek consultation as he/she might be at high risk of carrying the disease.
Diagnosis and Management
Diagnosis of thalassemia
can be made as early as 9-11 weeks in pregnancy using procedures such chorionic
villi sampling. Amniocentesis (analyzing the amniotic fluid may be carried
out at 16-20 weeks of pregnancy. Individuals can also be tested for thalassemia
through routine blood counts.
Early treatment of beta-thalassemia
has proved to be very effective in improving the quality of life of patients.
Long term transfusion support
is the backbone of conservative management in beta-thalassemia patients
to alleviate anemia.
Frequent blood transfusions
usually lead to iron overload that is countered by iron chelation therapy
to prevent damage to the internal organs.
In recent years, bone marrow
transplantation has shown promise in many patients with beta-thalassemia
where a successful transplant can eliminate the patients’ dependency on
Treatment of beta-thalassemia
major is currently an expensive option and has great financial implications
for any health authority where the disease has a high prevalence.
The baseline results for
the total lifetime treatment costs for a patient with beta-thalassemia
(up to 60 years of age) are estimated to be $416,000; thus, an average
of about $7000 annually.
Untreated beta thalassemia
eventually leads to death usually by heart failure; therefore genetic testing,
counseling, and prenatal diagnosis are very important in the prevention,
management and treatment of this disease.
In some endemic regions,
such as Mediterranean countries, long-established control programs have
achieved 80-100% prevention of newly affected births.
World Epidemiology of Thalassemia
Thalassemia was originally
thought to be a disease limited to the Mediterranean region, however it
is now known that it occurs widely throughout many parts of the world.
Thalassemia has been identified
across southern Europe from Portugal to Spain, Italy and Greece, as well
as in a number of central European countries and parts of the former Soviet
Thalassemia also affects
the Middle East through to Iran, Pakistan, India, Bangladesh, Thailand,
Malaysia, Indonesia and southern China, as well as countries along the
north coast of Africa and in South America.
Population migration and
intermarriage between different ethnic groups has introduced thalassemia
in almost every country of the world, including northern Europe where thalassemia
did not previously exist and where now it is becoming a major public health
While reliable sources estimate
that about 1.5% of the global population -- 80 million- 90 million people
-- are carriers of beta-thalassemia, with about 60,000 affected children
born annually, the great majority in the developing world, it is certain
that coming updated figures will demonstrate that those are gross underestimates.
There is still little accurate
data available on carrier rates (gene frequencies) in many population groups,
particularly in areas of the world known or expected to be heavily affected.
According to the records
of the Thalassemia International Federation, however, only about 200,000
patients with thalassemia major are alive and registered as receiving treatment
around the world.
Beta-thalassemia is endemic
in almost all countries of the Arab world probably due to the historical
presence of malaria in the region, and the high level of consanguinity.
Carrier frequencies of beta-thalassemia
vary from 1% to 5%.
The molecular basis of beta-thalassemia
has been extensively studied in various Arab countries. A total of more
than 60 mutations in the beta-globin gene have been reported in patients
with beta-thalassemia in the Arab world.
A recent genetic study in
Dubai demonstrated the presence of 50 mutations in the UAE population.
As expected, each Arab country, Mediterranean or Asian, has its own characteristic
spectrum of mutations.
While some mutations appear
in most countries, others seem to be regionally restricted paving the way
to studies on their historical origins.