Updated: 3/19/2020

Sideroblastic Anemia

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  • A 35-year-old man presents to the clinic for follow-up for treatment of latent tuberculosis. He is a recent immigrant to the United States from Mexico and started taking isoniazid 2 months ago after he was diagnosed with latent tuberculosis at an occupational health visit. Physical examination is notable for decreased sensation to pinprick in his lower extremities. A bone marrow aspirate is obtained and after staining with Prussian blue, the finding in the image is observed.

  • Overview
    • sideroblastic anemias are a group of inherited and acquired anemias in which iron accumulates in the mitochondria of erythrocyte precursors
      • ringed sideroblasts (iron-laden erythrocytes with Prussian-blue stained mitochondria) seen on bone marrow aspirate
  • Epidemiology
    • incidence
      • rare
    • demographics
      • X-linked recessive type of inherited sideroblastic anemia occurs more commonly in males
      • median age of occurence of primary acquired sideroblastic anemia is 74 years of age
    • risk factors
      • alcoholism
      • vitamin B6 deficiency
      • lead poisoning
      • copper deficiency
  • Pathophysiology
    • pathophysiology
      • mitochondrial pathways in erythrocyte precursors are disrupted, leading to accumulation of iron in the mitochondria
        • excessive iron deposits in erythroblasts form a ring around the nucleus, making a ringed sideroblast
      • heme synthesis is impaired, leading to ↓ heme production and abnormal RBCs (see Heme Metabolism)  
        • X-linked sideroblastic anemia
          • mutation in ALAS2 gene which encodes ALA synthase, the first enzyme of the heme synthesis pathway
            • vitamin B6 (pyridoxine) is a necessary cofactor for ALA synthase
        • isoniazid
          • disrupts conversion of vitamin B6 (pyridoxine) to its active cofactor
        • chronic alcohol use
          • impairs vitamin B6 metabolism
          • toxic effects on mitochondrial protein synthesis
        • lead poisoning
          • inhibits several enzymes involved in heme synthesis
            • ALA dehydratase
            • ferrochelatase
  • Genetics
    • inheritance pattern
      • X-linked (inherited sideroblastic anemia)
    • mutations
      • ALAS2 gene
        • encodes for ALA synthase
  • Prognosis
    • highly variable depending on cause
      • anemia due to reversible causes (i.e., alcohol and drugs) do not have long-term sequelae
    • secondary hemochromatosis (from transfusions) and leukemia are major causes of death
  • Symptoms
    • general symptoms of anemia 
      • fatigue
      • weakness
      • dyspnea on exertion
    • lack of coordination (cerebellar symptoms)
    • diarrhea
  • Physical exam 
    • growth delay in children
    • ataxia
    • ↓ deep-tendon reflexes
    • incoordination
    • dyspnea
    • muscular weakness
  • Serum labs
    • ↑ serum iron and ferritin
    • ↓ TIBC
    • ↓ or normal MCV
  • Histology
    • peripheral blood smear 
      • hypochromic RBCs
      • Pappenheimer bodies in RBCs 
        • abnormal basophilic granules of iron
      • low reticulocyte count
    • bone marrow stained with Prussian blue 
      • ringed sideroblasts 
        • diagnostic hallmark of all sideroblastic anemias
  • Iron deficiency anemia
    • key distinguishing factor
      • ↓ serum iron and ferritin
  • Megaloblastic anemia
    • key distinguishing factor
      • megaloblastic changes seen on peripheral blood smear and bone marrow rather than ringed sideroblasts
  • Medical pyridoxine (vitamin B6) supplementation
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