There are two main types of thalassemia:
Alpha thalassemia - this
is rare in Caucasians. It is common in people from the Far East.
Beta thalassemia - this is
covered below. There are two types:
- Beta thalassemia major is
a disease that causes severe anemia (lack of hemoglobin), along with disabilities
that require medical care, mainly multiple blood transfusions, throughout life.
It predominantly affects families of Mediterranean origin, both Jews and non-Jews.
There are in addition complex types of thalassemia, one of which is called thalassemia
intermedia and another sickle cell thalassemia, which is a combination of sickle
cell anemia and thalassemia. These are less severe than regular beta thalassemia
- Beta thalassemia minor, which
is the condition suffered by carriers of an abnormal gene for beta thalassemia major,
is much more common and manifests as mild anemia that does not cause medical problems
in day-to-day life and does not usually require any treatment.
What are the signs of beta thalassemia major?
The disease is usually diagnosed a few months after birth because of the onset of
pallor (paleness), which is sometimes accompanied by mild jaundice, an enlarged
spleen, anorexia (loss of appetite) and low body weight.
In such cases, a blood count should be performed, the results of which may indicate
that the child has the disease.
Patients need to be constantly monitored.
They require blood transfusions - sometimes very frequently.
These children have significantly delayed growth.
There are also typical changes in the structure of the face and skull.
Are carriers (with beta thalassemia minor) healthy?
The carriers, who have beta thalassemia minor, are mostly completely healthy and
suffer from no signs or symptoms of the disease. Most are detected when they undergo
a blood count for some other purpose, but there are some cases, mainly in women
who lose a lot of blood in menstruation, in whom the anemia reaches the stage where
it may cause slight weakness, usually transient without requiring intervention,
fatigue, and lack of concentration. These signs are very similar to those found
in the anemia caused by iron deficiency. The two are distinguished by carrying out
appropriate tests in order to prevent the administration of iron to beta thalassemia
carriers who do not need it.
In which populations is the disease common?
The disease is common in peoples from the Mediterranean basin area, mainly those
from Greece, Turkey, Syria, Lebanon, Iraq, North African countries, Iran, India,
Yemen and Kurdistan.
A diagram showing one example of how beta thalassemia
is inherited. The beta globin gene is located on chromosome 11. A child inherits
two beta globin genes-one from each parent. In this example, each parent has one
altered beta globin gene.
Can a child with this disease be cured?
Beta thalassemia major patients need repeated blood transfusions in order to maintain
a reasonable level of hemoglobin. These have to be given throughout the patient's
life. Complications of repeated blood transfusions become apparent after some years
and are a result of the accumulation of surplus iron in the various body tissues.
In the past this caused death in the third decade of life, but nowadays the patients
receive special injections of a drug called Desferral that helps them excrete surplus
iron and improves the length and quality of their life.
Recently, trials involving genetic treatment have commenced. The healthy gene is
inserted into the precursor cell of the red blood cells in the bone marrow. In another
decade, it may be possible to cure the disease in this way.
Today, efforts are directed towards early prenatal diagnosis in order to prevent
the birth of children with this disease. In a number of countries in which beta
thalassemia used to be very common, the prevalence of the disease has been significantly
reduced. In several countries, especially in the Mediterranean area, there are very
active programs that have resulted in the almost total disappearance of affected
children born to families interested in prevention.
Beta thalassemia major is transmitted by autosomal recessive inheritance.
Beta thalassemia major is fully expressed.
What is the risk of recurrence in a subsequent pregnancy?
If both parents are carriers of beta thalassemia major, each has one normal gene
and one abnormal gene. This carrier state is beta thalassemia minor. In every pregnancy
there is a 25% chance that the fetus will receive two copies of the abnormal gene,
one from his/her mother and one from his/her father, and such a fetus will have
beta thalassemia major. In addition, 50% of the offspring of such a marriage will
be carriers, i.e. they will have beta thalassemia minor like their parents. When
only one of the parents is a carrier, there is no risk that any of their children
will have beta thalassemia major; however, in such a family there is a 50% chance
that the child will be a carrier and will therefore have beta thalassemia minor,
like the parent.
The risk for more distant relatives depends on the result of their blood count and
hemoglobin electrophoresis tests. If a person is found to be a carrier, his or her
partner should undergo the same test.
Associated features that can be demonstrated in tests performed during pregnancy
There are no specific ultrasound signs and no associated defects.
The gene for the disease and the location
Beta globin, responsible for beta thalassemia, is situated on chromosome 11p15.
Alpha globin, responsible for alpha-thalassemia, is situated on chromosome 16p13.
A direct test can be performed to identify the mutation in the gene by testing for
the common mutations. See: Testing the disease-causing gene for mutations that are
common in a specific ethnic group - autosomal recessive diseases.
What should couples from the Mediterranean basin area do?
The first step is a test to determine whether the partners carry an abnormal beta
thalassemia gene. For this, at least one of the partners must undergo a specific
blood test (see below).
Where are the blood tests for identifying carriers performed?
A full blood count, which can detect carriers of an abnormal beta thalassemia gene,
is routinely performed on every pregnant woman. If the results of this test indicate
that she may be a beta thalassemia carrier, there are further tests that can be
done, such as hemoglobin electrophoresis, that can be carried out in any large hematological
center. If the blood test results show beyond doubt that the woman is not a carrier
of the abnormal gene, there is no risk that the couple's children will have this
disease. However, if the results of the test are unclear or the woman is found to
be a carrier, the couple is invited to come for further testing. If only one of
the partners is a carrier, there is no risk that any of their children will have
the disease. However, if both partners are carriers, there is a 25% risk in every
pregnancy that they will have a child with beta thalassemia major. Such couples
should be referred to a genetic counseling clinic for an explanation and recommendations
as to what further tests should be performed.
Carrier status testing in relatives of patients with beta thalassemia
It is important that relatives of patients with beta thalassemia clarify which mutations
are present in the patient or parents in their family in order to ascertain that
they are included in the battery of mutations routinely tested for - otherwise it
will be necessary to expand the list of mutations tested for and/or examine the
partner. This will be discussed in
genetic counseling. See also: Introduction to cystic fibrosis, Gaucher disease, Canavan disease,
familial dysautonomia, Bloom syndrome and Fanconi anemia.
Diagnosis can be made in the first trimester of pregnancy by examination of the
or the amniotic fluid cells. However, before it is possible to do this, the mutations
in the gene must first be determined in the parents by performing a special DNA
test. In most people this can be performed rapidly, but occasionally a lot of time
is required in order to characterize the mutations. It is therefore advisable to
do this at an early stage, if possible before pregnancy. The fetus can then be tested
for beta thalassemia. In all cases of families with affected family members or where
both partners have been found to be carriers, or if there is a doubt concerning
their carrier status, they should be referred to a genetic institute for further
What should the parents do when they learn that they may have a fetus with beta
Prenatal diagnosis carried out in every pregnancy will allow carrier parents to
have only healthy children who do not have beta thalassemia major. When prenatal
diagnosis indicates that the fetus is affected, the pregnancy can be terminated
using medical methods. In cases where both parents are carriers, therefore, it is
very important that the mother undergoes prenatal diagnosis in every pregnancy in
order to identify an affected fetus in the early stages of gestation, even if the
couple already has healthy children.