Inherited microcytic anemias

Abstract

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.

Graphical abstract

Figure 1.

Classification of microcytic anemias. In the middle of the figure is a schematic representation of the prosthetic group of hemoglobin with a protoporphyrin ring (with iron) and the globin chains. In the top panel (light blue) is the classification of microcytic anemias caused by alterations of globin chain synthesis. In the right panel (gray) is the classification of microcytic anemias caused by impairment of heme synthesis. In the bottom panel (pink) is the classification of microcytic anemias caused by iron metabolism defects. AD, autosomal dominant inheritance; AR, autosomal recessive inheritance; XLR, X-linked recessive inheritance.