Hemoglobinopathy is a genetic defect that causes abnormal structure of one of the globin
chains of the hemoglobin molecule. Thalassemia is a genetic defect resulting in the
production of an abnormally low quantity of a given hemoglobin chain or
chains. (Table H-2)
Table H-2 Hemoglobin Disorders: An Overview ||Download (.pdf)
Table H-2 Hemoglobin Disorders: An Overview
|Sickle cell syndromes||Sickle cell trait (Hb S heterozygotes)|
|Sickle cell anemia (Hb S homozygotes)|
|Sickle B thalassemia|
|Sickle cell C disease (hemoglobin C disease)|
|Sickle cell SC disease|
|Sickle cell D disease|
|Sickle cell SD disease|
|No sickling and crystallization||Hemoglobin E disease|
|Unstable Hemoglobins||Congenital Heinz body hemolytic anemia|
|Thalassemias (Cooley Anemias)||α-Thalassemia|
|β-Thalassemia (minor, major)|
|Hemoglobin Variants||Fetal hemoglobin (F)|
|Hemoglobin A2, G, D, J, H|
Genetically inherited hemolytic anemia, usually mild
and often inapparent until adulthood. Mainly encountered in populations of
African descent but also in populations of Sicilian and Hispanic descent.
CC Disease; Hemoglobinopathy C.
Hemolytic anemia with moderate reduction in red cell
lifespan. In the oxyhemoglobin state, hemoglobin C is
less soluble than normal hemoglobin, thus forming
intraerythrocytic crystals (tactoids); deoxygenation further reduces
solubility and increases blood viscosity. Patients with hemoglobin C disease
have a survival advantage in areas of endemic Plasmodium falciparum
Prevalence in the general population is 0.017% in
African Americans but approximately 0.03% in Northern Africa. No sex
Autosomal codominant (biparental inheritance).
The beta gene cluster is on chromosome 11.
The double helix of hemoglobin C is composed of
two normal alpha-chains and two variant beta-chains, in which glutamic acid
is replaced by lysine at position 6. Hemoglobin C is unstable and tends to
precipitate in erythrocytes where it crystallizes. This changes the physical
properties of the erythrocytic membrane (decreased deformability and
increased viscosity of blood). These crystal-containing red blood cells are
removed by the spleen, which becomes enlarged with time (splenomegaly).
Examination of the erythrocytes (blood smear) reveals
several morphologic disorders (caused by crystallization of hemoglobin):
target cells mainly, but also appearance of an off-center target, occasional
pyknotic spherocytes, and polychromasia. Diagnosis is established by
hemoglobin electrophoresis (100% hemoglobin C in homozygotes, up to
35% in heterozygotes). Reticulocyte count and lactic acid dehydrogenase
levels determine the extent of hemolysis.
Except for mild-to-moderate hemolytic anemia,
most patients remain asymptomatic until adulthood. Symptoms usually consist
of joint and musculoskeletal pain, visual disorders (retinopathy as a result
of iron deposition in the ...