Sideroblastic anemias are a diverse group of anemias characterized by the presence of ringed sideroblasts (erythroblasts with perinuclear iron-engorged mitochondria). Sideroblastic anemias may be acquired or congenital. Acquired sideroblastic anemia is frequently associated with myelodysplastic syndrome (but may be produced by drugs or toxins) and causes a macrocytic anemia. Congenital sideroblastic anemia is caused by one of numerous X-linked or autosomal mutations and is usually a microcytic-hypochromic anemia with increased serum iron and ferritin and transferrin saturation.
(See also Overview of Decreased Erythropoeisis.)
Sideroblastic anemias are characterized by inadequate marrow utilization of iron for heme synthesis despite the presence of adequate or increased amounts of iron (iron-utilization anemias). Sideroblastic anemias are sometimes characterized by the presence of polychromatophilia, and stippled RBCs (siderocytes).
In both acquired and congenital sideroblastic anemia, heme synthesis is impaired due to the inability to incorporate iron into protoporphyrin, leading to the formation of ringed sideroblasts.
Acquired sideroblastic anemias are often part of a
Less common causes include
Deficient reticulocyte production, intramedullary death of RBCs, and bone marrow erythroid hyperplasia (and dysplasia) occur. Although hypochromic RBCs are produced, other RBCs may be large, producing normocytic or macrocytic indices; if so, variation in RBC size (dimorphism) usually produces a high RBC distribution width (RDW).
The most common congenital sideroblastic anemia is an X-linked form caused by heterozygous germline mutations in the ALAS2, a gene involved in heme biosynthesis. Pyridoxine (B6) is an essential cofactor for this enzyme, thus patients may respond to pyridoxine supplementation. Numerous other X-linked, autosomal and mitochondrial forms have been identified with mutations in genes involved in heme synthesis. RBCs are usually microcytic and hypochromic, but this is not always the case.
Sideroblastic anemia is suspected in patients with microcytic anemia or a high RDW anemia, particularly with increased serum iron, serum ferritin, and transferrin saturation (see Iron Deficiency Anemia). The peripheral smear shows RBC dimorphism. RBCs may appear stippled. Bone marrow examination is necessary and reveals erythroid hyperplasia. Iron staining reveals the pathognomonic iron-engorged perinuclear mitochondria in developing RBCs (ringed sideroblasts). Other features of myelodysplasia, such as cytopenias and dysplasia, may be evident. Serum lead is measured if sideroblastic anemia has an unknown cause.