Anemia, Sideroblastic

KEY FEATURES

• Heterogeneous group of disorders in which reduced hemoglobin synthesis occurs because of reduced ability to synthesize heme or an impaired ability to incorporate heme into protoporphyrin IX

• Iron accumulates, particularly in mitochondria

• Modern classification divides sideroblastic anemia into two categories

  • Dyserythropoiesis (ie, hypohepcidinemia)

  • Transfusion-dependence (eg, myelodysplastic neoplasms, thalassemia)

• Most often it is a subtype of myelodysplastic neoplasms

• Other causes include chronic alcohol use disorder, lead poisoning, copper deficiency (hypocupremia), medications (isoniazid, chloramphenicol), and chronic infection or inflammation

• Inherited forms are usually X-linked but rare recessive forms have been documented

CLINICAL FINDINGS

• Symptoms of anemia; no other specific clinical features

• Hypocupremia

  • Normocytic anemia in two-thirds of cases; macrocytic in remainder

  • Zinc level is often elevated

  • Neutropenia or thrombocytopenia may be present

  • Myelopathy or demyelinating peripheral neuropathy in some patients

DIAGNOSIS

• Anemia usually moderate, hematocrit 20–30%

• Mean corpuscular volume (MCV)

  • Usually normal or slightly increased in sideroblastic subtype of myelodysplastic neoplasms

  • Usually low in other subtypes (especially inherited forms), leading to confusion with iron deficiency

• Peripheral blood smear characteristically shows dimorphic population of red blood cells (RBC): one normal and one hypochromic

• Coarse basophilic stippling of RBCs and serum lead level elevated in lead poisoning

• Bone marrow iron stain shows generalized increase in iron stores and ringed sideroblasts (RBCs with iron deposits in mitochondria encircling the nucleus) and marked erythroid hyperplasia (resulting from ineffective erythropoiesis)

• Serum iron level and transferrin saturation are high

TREATMENT

• Occasionally, transfusion is required for severe anemia

• Recombinant erythropoietin therapy is not usually effective

• Oral pyridoxine (50–200 mg/d) occasionally useful

• Removal of offending toxins and drugs is needed in the secondary acquired forms

• Hypocupremia: administer copper sulfate (2.5 mg orally twice daily)

  • Associated with high hematologic response rate but low neurologic response rate

  • Exogenous or endogenous zinc exposure needs to be eliminated

• Luspatercept

  • FDA approved for myelodysplastic neoplasms with ringed sideroblasts

  • It is a TGF-β ligand trap that promotes erythroid maturation and reduces need for transfusion