Sideroblastic Anemia

Excerpt

Sideroblastic anemia is a rare type that results from abnormal utilization of iron during erythropoiesis. There are different forms of sideroblastic anemia, and all forms are defined by the presence of ring sideroblasts in the bone marrow. Ring sideroblasts are erythroid precursors containing deposits of non-heme iron in mitochondria, forming a ring-like distribution around the nucleus. The iron-formed ring covers at least one-third of the nucleus rim (see Images. Sideroblastic Anemia and Ringed Sideroblasts).

The hemoglobin molecule contains a crucial prosthetic group called heme, integral to its oxygen-carrying function. Structurally, heme consists of a porphyrin ring formed by 4 pyrrole rings connected by methine bridges at the alpha positions, with a central iron atom coordinated within the ring. This iron center enables hemoglobin to bind and transport oxygen efficiently to tissues throughout the body. Other functions of heme apart from the formation of hemoglobin include gas sensing, signal transduction, biological clock, circadian rhythm, and microRNA processing.

Sideroblastic anemia results from abnormal erythropoiesis during heme production. Eighty-five percent of heme is produced in the cytoplasm and mitochondria of the erythroblast cells, while the remainder is produced in hepatocytes. In the Shemin pathway, also known as the heme biosynthesis pathway, 8 enzymes catalyze sequential reactions for heme synthesis. These enzymes include aminolevulinic acid synthase, porphobilinogen synthase, porphobilinogen deaminase, uroporphyrinogen III synthase, uroporphyrinogen decarboxylase, coproporphyrinogen oxidase, protoporphyrinogen oxidase, and ferrochelatase.

There are 2 forms of sideroblastic anemia: hereditary and acquired. Hereditary sideroblastic anemia primarily causes microcytic anemia due to defective heme synthesis, but certain mutations can lead to normocytic or, in rare cases, macrocytic anemia. Unlike iron deficiency anemia, where there is a depletion of iron stores, patients with sideroblastic anemia have normal or high iron levels. Other microcytic anemias include thalassemia and anemia of chronic disease.

Refractory anemia with ring sideroblasts (RARS) is an acquired form of sideroblastic anemia that is classified as a type of myelodysplastic syndrome (MDS), which is characterized by anemia and the presence of 15% or more ring sideroblasts in the marrow. Generally, the patient presents with normochromic, normocytic anemia with overall erythroid hyperplasia as the body attempts to compensate for ineffective erythropoiesis. The hemoglobin level is generally 9 to 12 g/dL, though lower levels may be present. The red blood cells may show dimorphism (with both hypochromic and normochromic populations) and variable degrees of dyserythropoietic and occasional megaloblastic features. Granulopoiesis and megakaryocytopoiesis are normal. Platelet and neutrophil counts can vary but are typically normal or mildly increased.