Sideroblastic anemia

Sideroblastic anemia is caused by abnormal production of red blood cells (erythrocytes),^[1] usually as part of myelodysplastic syndrome,^[2] which can evolve into hematological malignancies (especially acute myelogenous leukemia). The body has iron available but cannot incorporate it into hemoglobin. Sideroblasts are seen, which are nucleated erythrocytes with granules of iron in their cytoplasm.^[3]

"Sideroachrestic anemia" is sometimes used as a synonym for sideroblastic anemia.

Classification

Sideroblastic anemia is typically divided into subtypes based on its cause.

• Hereditary sideroblastic anemia may be X-linked^[4] or autosomal.

GLRX5 has also been implicated.^[5]

• Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause.

Symptoms

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.^[6]

Causes

The common feature of these causes is a failure to completely form heme molecules, whose biosynthesis takes place partly in the mitochondrion. This leads to deposits of iron in the mitochondria that form a ring around the nucleus of the developing red blood cell. Sometimes the disorder represents a stage in evolution of a generalized bone marrow disorder that may ultimately terminate in acute leukemia.

• Toxins: lead or zinc poisoning
• Drug-induced: ethanol, isoniazid, chloramphenicol, cycloserine
• Nutritional: pyridoxine or copper deficiency
• Genetic: ALA synthase deficiency (X-linked, associated with ALAS2)^[7]

Diagnosis

Ringed sideroblasts are seen in the bone marrow.

The anemia is moderate to severe and dimorphic with marked anisocytosis and poikilocytosis. Basophilic stippling is marked and target cells are common. Pappenheimer bodies are present. The MCV is decreased (ie. a microcytic anemia). 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 TIBC is normal to decreased. Stainable marrow hemosiderin is increased.

Laboratory findings

• Increased ferritin levels
• Decreased total iron-binding capacity
• Hematocrit of about 20-30%
• Serum Iron: High
• High transferrin saturation
• The mean corpuscular volume or MCV is usually normal or slightly increased; although it may occasionally be low, leading to confusion with iron deficiency.^[1]
• 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.

Treatment

Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietin therapy.^[8] Some cases have been reported that the anemia is reversed or heme level is improved through use of moderate to high doses of pyrodoxine (Vitamin B6.) In severe cases of SBA, bone marrow transplant is also an option with limited information about the success rate. Some cases are listed on MedLine and various other medical sites. In the case of isoniazid-induced sideroblastic anemia, the addition of B6 is sufficient to correct the anemia.

See also

• Anemia
• Siderosis

References

External links

• Sideroblastic Anemias: Introduction - Information Center for Sickle Cell and Thalassemic Disorders
• A concise description of this group of diseases from the Iron Disorders Institute
• Anemia, Sideroblastic at NIH's Office of Rare Diseases