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Thalassemia
Thalassaemia is an inherited disease of the erythrocytes (the red blood
cells), classified as a hemoglobinopathy: the genetic disorder results
in synthesis of an abnormal hemoglobin molecule. The blood cells are
vulnerable to mechanical injury and die easily. To survive, many people
with thalassaemia need blood transfusions at regular intervals.
This disease tends to occur in areas with a past history of malaria,
since it confers a degree of protection against that disease. In that
respect it resembles another genetic disease, sickle-cell anemia.
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Classification
The thalasassemias are classified according to which chain of the globin
molecule is affected: in α thalassemia, the production of α globin is
deficient, while in β thalassemia the production of β globin is
defective.
Alpha thalassemias
α thalassemias result in excess β chain production in adults and excess
γ chains in newborns. The excess β chains form unstable tetramers that
have abnormal oxygen dissociation curves.
There are four genetic loci for α globin. The more of these loci that
are deleted or affected by mutation, the more severe will be the
manifestations of the disease.
If all four loci are affected, the fetus cannot live once outside the
uterus: most such infants are dead at birth with hydrops fetalis, and
those who are born alive die shortly after birth. They are edematous and
have little circulating hemoglobin, and the hemoglobin that is present
is all tetrameric γ chains (hemoglobin Barts).
If three loci are affected, Hemoglobin H disease results. Two unstable
hemoglobins are present in the blood, both hemoglobin Barts and
hemoglobin H (tetrameric β chains). There is a microcytic hypochromic
anemia with target cells and Heinz bodies on the peripheral blood smear.
The disease may first be noticed in childhoood or in early adult life,
when the anemia and splenomegaly is noted.
If two of the four α loci are affected, α-thalassemia trait results. Two
α loci permit nearly normal erythropoiesis, though there is a middle
microcytic hypochomic anemia. There is a high prevalence (about 30%) of
deletion of one of the two α loci on chromosomes of people of recent
African origin, and so the inheritance of two such chormosomes is not
uncommon. The disease in this form can be mistaken for iron deficiency
anemia and treated inappropriately with iron.
If one of the four α loci is affected, there is minimal effect. Three α-globin
loci are enough to permit normal hemoglobin production, and there is no
anemia or hypochromia in these people. They have been called α
thalassemia carriers.
Beta thalassemias
In β thalassemia, excess α chains are produced, but these do not form
tetramers: rather, they bind to the red blood cell membranes, producing
membrane damage. The severity of the damage depends on the nature of the
mutation. Some mutations (βo) prevent any formation of β chains; others
(β+) allow some β chain formation to occur.
There are two β globin genes. If both have thalassemia mutations, a
severe anemia called β thalassemia major or Cooley's anemia results.
Untreated, this results in death before age twenty: treatment consists
of periodic transfusion; splenectomy if splenomegaly is present, and
treatment of transfusion-caused iron overload. Cure is possible by bone
marrow transplantation.
If only one β globin gene bears a mutation, β thalassemia minor results.
This is a mild anemia with microcytosis. Symptoms are weakness and
fatigue.
Thalassemia in combination with other hemoglobinopathies
Thalassemia can co-exist with other hemoglobinopathies. The most common
of these are:
hemoglobin E/thalassemia: common in Cambodia and Thailand, clinically
similar to β thalassemia major
hemoglobin S/thalassemia, common in African and Mediterranean
populations; clinically similar to sickle cell anemia, with the
additional feature of splenomegaly
hemoglobin C/thalassemia: common in Mediterranean and African
populations, hemoglobin C/βo thalassemia causes a moderately severe
hemolytic anemia with splenomegaly; hemoglobin C/β+ thalassemia produces
a milder disease.
Clinical suspicion
Microcytic hypochromic anemia without increase
in reticulocyte count not caused by iron deficiency with morphological abnormalities
in peripheral blood smear. In severe cases bone abnormalities & splenomegaly.
Diagnosis
Hgb electrophoresis.
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