Inherited microcytic
anemias can be broadly classified into 3 subgroups: (1) defects in
globin chains (
hemoglobinopathies or
thalassemias), (2) defects in
heme synthesis, and (3) defects in
iron availability or
iron acquisition by the erythroid precursors. These conditions are characterized by a decreased availability of
hemoglobin (Hb) components (
globins,
iron, and
heme) that in turn causes a reduced Hb content in red cell precursors with subsequent delayed erythroid differentiation.
Iron metabolism alterations remain central to the diagnosis of microcytic
anemia, and, in general, the
iron status has to be evaluated in cases of microcytosis. Besides the very common microcytic
anemia due to acquired
iron deficiency, a range of hereditary abnormalities that result in actual or functional
iron deficiency are now being recognized.
Atransferrinemia, DMT1 deficiency,
ferroportin disease, and
iron-refractory iron deficiency anemia are hereditary disorders due to
iron metabolism abnormalities, some of which are associated with
iron overload. Because causes of microcytosis other than
iron deficiency should be considered, it is important to evaluate several other red blood cell and
iron parameters in patients with a reduced mean corpuscular volume (MCV), including mean corpuscular hemoglobin, red blood cell distribution width, reticulocyte
hemoglobin content, serum
iron and serum
ferritin levels, total
iron-binding capacity,
transferrin saturation,
hemoglobin electrophoresis, and sometimes reticulocyte count. From the epidemiological perspective,
hemoglobinopathies/
thalassemias are the most common forms of hereditary microcytic
anemia, ranging from inconsequential changes in MCV to severe
anemia syndromes.