Anemia, Sideroblastic



  • Sideroblastic anemia (SA) is a disorder of iron utilization in the erythroblast resulting in ineffective erythropoiesis and variable systemic iron overload leading to anemia. It is characterized by the presence of ringed sideroblasts in the bone marrow.
  • This disease process can be congenital or acquired.
  • Although the body has available iron stores, iron cannot be incorporated into the hemoglobin, resulting in granules of iron that accumulate in the mitochondria where heme is produced.


  • SAs are uncommon. Incidence and prevalence are not well studied.
  • Acquired forms are more common than hereditary forms and usually occur in older adults; present in 25–30% of alcoholics with anemia, most commonly with folate and vitamin B6 deficiency
  • Hereditary forms vary in severity, usually manifesting in childhood.

Etiology and Pathophysiology

  • Inability to use iron for the production of hemoglobin due to inherited or acquired impairment
  • Ineffective erythropoiesis despite abundance of iron in the body
  • Increased GI absorption of iron leading to iron overload
  • Inability to use iron for heme synthesis results in sideroblasts, which are abnormal erythroblasts with granules of iron accumulated in the mitochondria, forming a ring around the nucleus.
  • Congenital SAs are inherited forms of SA resulting from genetic defects listed in the “Genetics” section.
  • Refractory anemia with ring sideroblasts (RARS), RARS with thrombocytosis (RARS-T), refractory cytopenia with multilineage dysplasia and ringed sideroblasts (RCMD-RS), and pure SA (PSA) are subtypes of the myelodysplastic syndromes (MDS) related to clonal over proliferation of hematopoietic cell lines:
    • RCMD-RS tend to have more severe anemia, have decreased survival, and with 5% evolve into acute leukemia (1).
  • Acquired SA is usually reversible when the inciting factor is removed. Acquired SA is more common than congenital SA and can be caused by the following:
    • Alcohol
    • MDS
    • Isoniazid
    • Pyrazinamide
    • Chloramphenicol
    • Cycloserine
    • Azathioprine
    • D-penicillamine
    • Linezolid
    • Fusidic acid (1)
    • Busulfan (1)
    • Melphalan (1)
    • Triethylenetetramine (1)
    • Dihydrochloride (1)
    • Lead poisoning
    • Zinc toxicity leading to copper deficiency
    • Copper deficiency
    • Pyridoxine deficiency
    • Hypothermia affecting mitochondrial functions


  • Can be X-linked, autosomal dominant (AD), or autosomal recessive (AR)
  • Congenital form can arise from multiple gene defects:
    • Defect in aminolevulinic acid synthase (ALAS-2 mutation): the first and rate-limiting enzyme in heme biosynthesis; most common congenital SA (X-linked)
    • A defect in the ABCB7 gene results in SA with spinocerebellar ataxia (X-linked).
    • Defect in mitochondrial amino acid transporter (SLC25A38) (AR) (2)
    • Defect in ferrochelatase (AR or AD)
    • Defect in glutaredoxin 5
    • Defect in thiamine transporter 1
    • Defect in mitochondrial proteins and exporters (AR)
    • SA with B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) (AR)
    • Pearson marrow pancreas syndrome results from defect in mitochondria of erythroblasts.

Risk Factors

  • Male gender (X-linked SA)
  • Family history of hereditary SA
  • Chronic alcohol abuse

General Prevention

Pyridoxine should be given to all patients on isoniazid to avoid anemia.

Commonly Associated Conditions

  • Iron overload or secondary hemochromatosis from transfused blood products
  • Transformation into acute leukemia is rare.
  • Alcohol abuse
  • Acute photosensitivity
  • Delayed motor development

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