HemoglobinopathiesIntroduction:
Hemoglobinopathies are genetic abnormalities of the hemoglobin molecule,
which is a complicated protein that provides structural integrity to the red blood
cell and allows the red blood cells to transport oxygen to the tissues and carbon
dioxide from the tissues to the lungs in an optimal way. There
are many inherited defects of the hemoglobin molecule and this translates into
such abnormalities as the sickle cell anemia, the hemoglobin C disease, hemoglobin
E disease, hemoglobin S-C disease and the thalassemia. See the distribution table
for more details on these conditions. As a brief overview it is important to note
that during fetal life there is a different hemoglobin present (hemoglobin F),
which is better suited for the fetal blood circulation where the lung function
is taken care of by the placenta. In the adult less than 2% of the total hemoglobin
consists of hemoglobin F, the remainder is hemoglobin A, which is the normal hemoglobin.
With hemoglobinopaties a higher percentage of hemoglobin F can be present in children
and adults, which is a clue during the diagnostic work-up.
Hemoglobin C Disease
About
2.5% of blacks in the US have this trait. It is a hemoglobinopathy where abnormal
hemoglobin is produced leading to an anemia similar to sickle cell anemia, but
not as severe. Hemoglobin C disease (in homozygotes) does not produce the abdominal
crises that are typical for sickle cell disease. An enlarged spleen (splenomegaly)
is typically present. The laboratory findings show a moderate anemia with 35 to
100% target cells. The smear also shows spherocytes and red blood cells that contain
crystals. The red blood cells do not show sickling, but some may be nucleated.
The decisive test is by electrophoresis that shows the hemoglobin C. Heterozygotes
are symptom free, but their red blood cells show central targeting. Even the more
symptomatic homozygotes usually do not have severe enough symptoms to warrant
treatment.
Hemoglobin S-C DiseaseThis hemoglobinopathy can occur in a child
where one parent has sickle cell anemia (hemoglobin S) and the other parent has
hemoglobin C disease. It is most commonly found in blacks. The symptoms are similar
to a patient with sickle cell anemia, but much milder. Frank hematuria (blood
in urine), spontaneous hip bone fractures (aseptic necrosis of the femoral head)
and retinal bleeding (retinal hemorrhages) are common. The blood tests show target
cells in blood smears with the occasional sickling as well, and hemoglobin S-C
on electrophoresis.
Hemoglobin E DiseaseThis hemoglobinopathy is quite common among
blacks and Southeast Asians (more than 15% carry the homozygous form), but is
rare among the Chinese. Depending on what genetic combination the patient has
the clinical presentation will be different. The mildest form is the heterozygote
with hemoglobin AE who will be asymptomatic. On the other hand, a homozygote with
hemoglobin E disease will have a mild anemia with target cells. The most severe
clinical condition is a patient heterozygous for hemoglobin E and beta-thalassemia.
These patients have some symptoms of thalassemia and have an enlarged spleen.
These patients require a close follow-up by a hematologist. All of these various
genetic forms of hemoglobin E disease can be diagnosed with the help of electrophoresis.
Hemoglobin S-Beta-Thalassemia DiseaseThis is a hemoglobinopathy
that has both the genetic defect of sickle cell anemia and of beta-thalassemia.
It occurs when children are born to parents who carry these two different genes.
As the diseases run in overlapping population groups, this combination is not
infrequent. Microcytic anemia is mild to moderate. There will be some sickled
red blood smells on a blood smear. Quantitative hemoglobin analysis shows that
hemoglobin A2 is greater than 3%, hemoglobin F is increased, hemoglobin A decreased
or even absent. Electrophoresis shows the exact hemoglobin constellation. Milder
cases often do not need to be treated; others who are symptomatic are treated
as explained under sickle cell anemia.
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