August 20, 2015 - Thalassemia Flashcards
Thalassemia
In general terms, a disorder where the globin molecule cannot be synthesized properly.
This should always be on your differential diagnosis for microcytic anemia.
Thalassemia and Malaria
Corresponds with malaria-rich areas. This is a case of heterozygote advantage in which a heterozygous individual is resistant to malaria, but does not suffer the effects of full-blown thalassemia.
Hb A
Composed of two alpha and two beta chains.
Hb F
Composed of two alpha and two gamma chains.
(usually before birth when it switches)
Hb A2
Composed of two alpha and two delta chains.
Relatively rare (only about 2% in this form)
Alpha Thalassemia
Decreased synthesis of the alpha globin chain. This is commonly due to the deletion of one or more alpha globin gene loci (there are 4 - two on each chromosome).
aa/aa is normal
-a/aa or a-/aa or aa/a- or aa/-a are all silent carriers
–/aa or aa/– is known as a heterozygous cis
a-/a- or -a/-a is known as heterozygous trans
a-/– is known as Hemoglobin H
–/– results in Hydrop fetalis with Hb Barts
Diagnosis of Alpha-Thalassemia
Molecular diagnosis using electrophoresis or liquid chromatography.
Beta Thalassemia
There are only two beta-globin alleles.
Mutations characterized by either ß0 which is no B-globin production, or ß+ which is reduced B-globin production.
Either way, the result is an excess of alpha-chains and not enough beta-chains.
ß/ß = Normal
ß/ß0 or ß/ß+ = Mild anemia
ß0/ß+ = Moderately severe anemia
ß0/ß0 = Severe anemia
Diagnosis of Beta-Thalassemia
Usually diagnosed around 6 months to 1 year of age as the beta-globin begins to be manufactured more and more and the gamma-globin is manufactured less and less.
Confirmed by molecular testing.
Iron Loading
Too much iron can cause organ failure and can be fatal. Beta-thalassemics often require blood transfusions regularly, which saves their lives, but they need to get rid of the excess iron that comes in the blood.
They must chelate the iron.
