Types
The WHO International Working Group on Morphology of MDS (IWGM-MDS) defined three types of sideroblasts:
Type 1 sideroblasts: fewer than 5 siderotic granules in the cytoplasm
Type 2 sideroblasts: 5 or more siderotic granules, but not in a perinuclear distribution
Type 3 or ring sideroblasts: 5 or more granules in a perinuclear position, surrounding the nucleus or encompassing at least one third of the nuclear circumference.Type 1 and type 2 are found in non-sideroblastic anemias. Type 3 is found only in sideroblastic anemia. Symptoms and signs
Symptoms of sideroblastic anemia include skin paleness, fatigue, dizziness, and enlarged spleen and liver. Heart disease, liver damage, and kidney failure can result from iron buildup in these organs. Causes
Causes of sideroblastic anemia can be categorized into three groups: congenital sideroblastic anemia, acquired clonal sideroblastic anemia, and acquired reversible sideroblastic anemia. All cases involve dysfunctional heme synthesis or processing. This leads to granular deposition of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Congenital forms often present with normocytic or microcytic anemia while acquired forms of sideroblastic anemia are often normocytic or macrocytic. Congenital sideroblastic anemia
X-linked sideroblastic anemia: This is the most common congenital cause of sideroblastic anemia and involves a defect in ALAS2, which is involved in the first step of heme synthesis. Although X-linked, approximately one third of patients are women due to skewed X-inactivation (lyonizations). Autosomal recessive sideroblastic anemia involves mutations in the SLC25A38 gene.
Basophilic stippling is marked and target cells are common. The mean cell volume is commonly decreased (i.e., a microcytic anemia), but it may also be normal or even high. The RDW is increased with the red blood cell histogram shifted to the left. Leukocytes and platelets are normal. Bone marrow shows erythroid hyperplasia with a maturation arrest.In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. The total iron-binding capacity of the cells is normal to decreased. Stainable marrow hemosiderin is increased. Classification
Sideroblastic anemia is typically divided into subtypes based on its cause. Hereditary or congenital sideroblastic anemia may be X-linked or autosomal.GLRX5 has also been implicated. Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause. Laboratory findings
Serum Iron: high
increased ferritin levels
decreased total iron-binding capacity
high transferrin saturation
Hematocrit of about 20-30%
The mean corpuscular volume or MCV is usually normal or low for congenital causes of sideroblastic anemia but normal or high for acquired forms. With lead poisoning, see coarse basophilic stippling of red blood cells on peripheral blood smear
Specific test: Prussian blue stain of RBC in marrow shows ringed sideroblasts. Prussian blue staining involves a non-enzymatic reaction of ferrous iron with ferrocyanide forming ferric-ferrocyanide, which is blue in color. A counterstain may be used to provide better visualization. Treatment
Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietin therapy.