Internal Medicine

Sideroblastic anaemia


Anaemia that results from abnormal utilization of iron during erythropoiesis.

Bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes) in sideroblastic anaemia | Paulo Henrique Orlandi Mourao, CC BY-SA 3.0,


Congenital sideroblastic anemia (CSAs):

Inherited conditions due to mitochondrial dysfunction due to defects in heme biosynthesis, iron biogenesis, or even generalized mitochondrial protein synthesis.

  • X-linked form (M/C, mainly in boys):
    • ALA2 mutation → ↓ δ-ALA synthase → ↑↑ Iron & ↓↓ heme
  • Autosomal recessive form: SLC25A38 mutations

Acquired sideroblastic anaemia:

  • Excessive alcohol use: Mitochondrial damage
  • Vitamin B6 (pyridoxine) deficiency
  • Lead poisoning: Denatures enzymes required for heme synthesis & ribonuclease
Classification of congenital and acquired sideroblastic anemias. | Cazzola, M., & Invernizzi, R. (2011). Ring sideroblasts and sideroblastic anemias. Haematologica, 96 6, 789-92 .


Heme production:

  • Cytoplasm & mitochondria of the erythroblast cells: 85%
  • Hepatocytes: 15%

Ring sideroblasts (in bone marrow):

Erythroid precursors containing deposits of non-heme iron in mitochondria forming a ring-like distribution around the nucleus.

  • Iron-formed ring covers at least ⅓ of the nucleus rim

WHO International Working Group on Morphology of MDS (IWGM-MDS) classification of sideroblasts:

  1. Type 1 sideroblasts: < 5 siderotic granules in cytoplasm
  2. Type 2 sideroblasts: ≥ 5 siderotic granules (no perinuclear distribution)
  3. Type 3 or ring sideroblasts: ≥ 5 granules in perinuclear position (surrounding the nucleus or encompassing at least ⅓ of nuclear circumference)
  • Type 1 & 2 found in non-sideroblastic anaemias. Type 3 is found only in sideroblastic anaemia.

Clinical features

Presentation similar to haemochromatosis (iron overload):

  • Pallor, fatigue, dizziness
  • Hepatosplenomegaly
  • Diarrhoea


  • Benign disorder responding to pyridoxine with substantial amelioration of anemia
  • Prevention and treatment of iron overload is also important and can be generally achieved through phlebotomy.

Congenital autosomal recessive sideroblastic anaemia:

  • Severe disease, not responsive to pyridoxine and with a clinical course very similar to that of thalassemia major.
  • Allogeneic stem cell transplantation should, therefore, be considered in young patients with this disease


  • Cardiovascular complications
  • Hepatic damage
  • Kidney failure


Complete blood count (CBC):

  • Congenital: MCV normal/↓
  • Acquired: MCV normal/↑

Peripheral blood smear (PBS):

  • Basophilic stippling
  • Pappenheimer bodies (iron)
  • Bone marrow biopsy: Ringed sideroblasts (ineffective haematopoiesis) → some found in PBS
Representative peripheral blood and bone marrow smears from a patient with X-linked sideroblastic anemia. (A) Peripheral blood smear showing many hypochromic and microcytic cells. May-Grünwald-Giemsa (MGG), x1,000. (B) Bone marrow smear showing erythroid hyper plasia: erythroblasts are small with abnormal condensation of nuclear chromatin and ragged cytoplasm with ill-defined edges. MGG, x1,000. (C) Bone marrow smear showing erythroblasts with defective hemoglobinization (left) and erythroblasts containing multiple Pappenheimer bodies (right). MGG, x1,250. (D) Bone marrow smear. Perls’ stain shows that most erythroid precursors are ring sideroblasts with at least five positive granules disposed in a ring surrounding a third or more of the circumference of the nucleus. x1,250. | Cazzola, M., & Invernizzi, R. (2011). Ring sideroblasts and sideroblastic anemias. Haematologica, 96(6), 789 LP – 792.

Iron studies:

  • ↑ Serum iron
  • ↑ Ferritin
  • ↓ TIBC


Manage iron overload:

  • Therapeutic phlebotomy “bloodletting”
  • Deferoxamine (iron-chelating agent)

Severe cases:

  • Bone marrow or liver transplantation

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