CASE FILES: BIOCHEMISTRY
Figure 12-1. Maturation of hemoglobin from the fetal form to the adult form.
In P-thalassemias, because of a defect in the P-globin gene, the y-chain cannot
be effectively replaced with the P-chain.
Thalassemias are named according to the affected globin chain: Thus,
a disorder of the a-chain would be an a-thalassemia, and a disorder of the
P-chain would be a P-thalassemia. There are two major forms of thalassemia,
one in which the P-globin chain is not produced (P0) and another in which
there is significantly reduced level of P-globin chain (P+). The positive cate-
gory includes variants with unusually high levels of HbF or HbA2, variants
with normal levels of HbA2, silent or benign variants, those that are inherited
in a dominant fashion, and variants that are not linked to the P-gene cluster.
A severe decrease in P-globin levels leads to the precipitation of the a-
chain, which in turn causes a defect in the maturation of the erythroid precur-
sor, and erythropoiesis thus reducing red cell survival. The profound anemia in
the affected individual stimulates the production of erythropoietin leading to
the expansion of bone marrow and subsequent skeletal deformities. The hyper-
plasia of the bone marrow induces increased iron absorption leading to the
deposition of iron in tissues. If the concentration of iron in the tissues becomes
too high, it can lead to organ failure and death if appropriate therapeutic steps
are not taken.
There are at least 200 p-thalassemia alleles that have been characterized to
date. P-Thalassemias are caused primarily by point mutations within the
P-globin gene and the neighboring flanking region. There are two exceptions