Biology of Disease

As a result of the coincident distribution of the genes for HbS and HbC,
heterozygotes for both Hbs are not uncommon producing HbSC disease. This
is milder than true sickle cell disease but patients can show practically all
the same complications. Furthermore, it is symptomatic in the heterozygous
state. There can also be co-inheritance of the sickle cell and thalassemia
genes, which generates a wide spectrum of clinical symptoms whose severity
depends on the type of thalassemia mutation (see below).

The Thalassemias

Thalassemia, from ‘thalassa’, which is Greek for ‘the sea’, are a group
of hemoglobinopathies originally discovered in people living near the

HEMOGLOBINOPATHIES

CZhhVg6]bZY!BVjgZZc9Vlhdc!8]g^hHb^i]:YLddY (+*

Heterozygotes, those with genes for HbA and HbS, have sickle cell
trait. Individuals typically have about 30% HbS and life expectancy
is about the same as for normal persons. The condition causes
relatively few problems except at high altitudes and when flying
in nonpressurized aircraft. Sickle cell disease, the homozygous
condition, is present in approximately 8% of American blacks
and may be as high as 45% in some African populations. It
is thought to cause 60 000 80 000 deaths in African children
annually. It may be asked why such a deleterious gene should
have persisted. The answer is probably that the possession of

a single HbS gene, that is sickle cell trait, increases resistance

to malaria caused by Plasmodiumspp (Chapter 2). Malaria is

typically endemic in areas where the sickle cell trait reaches high

levels (Figure 13.24). The same may also be true of thalassemia

(see below). The reason for resistance seems to be that as

Plasmodium parasites grow in the erythrocytes, they lower the

intracellular pH and generate hydrogen peroxide. The lower pH

promotes sickling of the erythrocytes and the hydrogen peroxide

damages cell membranes, which become more permeable to K+.

The resulting intracellular decrease in K+ kills the parasites.

BOX 13.4 Sickle cell trait and malaria

Figure 13.24 Areas of the world where sickle cell disease and thalassemia are

common.

Sickle cell anemia

HbC

Thalassemia