Patients have no specific clinical features other than those related to anemia. The anemia is usually moderate, with hematocrits of 20–30%, but transfusions may occasionally be required. In the sideroblastic subtype of MDS, the MCV is usually normal or slightly increased, as it when due to alcohol. In other types, the MCV is usually low (especially in the inherited forms) leading to confusion with iron deficiency. However, the serum iron level is elevated and the transferrin saturation is high. The peripheral blood smear characteristically shows a dimorphic population of red blood cells, one normal and one microcytic. In cases of lead poisoning, coarse basophilic stippling of the red cells is seen and the serum lead levels will be elevated.
The diagnosis is made by examination of the bone marrow. Characteristically, there is marked erythroid hyperplasia, a sign of ineffective erythropoiesis (expansion of the erythroid compartment of the bone marrow without the release of adequate mature red blood cells into the peripheral blood) (eFigure 13–6). The Prussian blue iron stain of the bone marrow shows a generalized increase in iron stores and the presence of ringed sideroblasts (erythroid cells with iron deposits in mitochondria encircling the nucleus). Occasionally, the anemia is severe enough to require red blood cell transfusions. These patients usually do not respond well to recombinant erythropoietin therapy, especially when transfusion requirements are significant. There are occasional responses to oral pyridoxine (50–200 mg/day). Removal of offending toxins and drugs is needed in the secondary acquired forms.
Refractory anemia with ringed sideroblasts. (Bone marrow aspirate, 50 ×.) Prussian blue iron stain. There are numerous erythroid precursors with iron-laden mitochondria encircling the nucleus. These are referred to as ringed sideroblasts. When more than 15% of erythroid cells are ringed sideroblasts, the diagnosis of refractory anemia with ringed sideroblasts is established. (Used, with permission, from L Damon.)
A rare form of sideroblastic anemia is now recognized that is due to copper deficiency (hypocupremia). The anemia is normocytic in two-thirds of cases and macrocytic in the remainder. The zinc level is usually elevated. Neutropenia or thrombocytopenia (or both) may also be present. Some patients have a myelopathy or demyelinating peripheral neuropathy. The bone marrow biopsy is usually interpreted as a "myelodysplastic syndrome" due to the presence of ringed sideroblasts and vacuolization of the myeloid and erythroid progenitors. The causes of hypocupremia include excess total body zinc (due to zinc-imbedded dental fillings or excessive oral zinc intake, eg, due to high levels of zinc in some Asian herbal preparations), or due to gastric bypass surgery. Treatment with copper sulfate (2.5 mg twice daily) is associated with a high hematologic response rate but a low neurologic response rate. Exogenous or endogenous zinc exposure needs to be eliminated.