Sideroblastic anemia

• Description: anemia caused by defective heme metabolism, which leads to iron trapping inside the mitochondria
• Etiology
  • Inherited: X-linked sideroblastic anemia due to a δ-ALA-synthase gene defect
    • ALA synthase, not ALA dehydratase t
  • Acquired
    • Vitamin B6 deficiency
    • Lead poisoning
    • Alcohol use disorder
    • Drugs (e.g., chloramphenicol, isoniazid, linezolid)
• Diagnostics
  • CBC: microcytic anemia c
    • Serum iron studies
    • High ferritin
    • High iron
    • High transferrin saturation
    • Normal/low TIBC
  • Peripheral blood smear
    • Basophilic stippling of RBCs t
      • Basophilic stippling represents the aggregation and precipitation of residual rRNA within the red blood cell cytoplasm. Lead inhibits the enzyme pyrimidine 5’-nucleotidase. This enzyme normally degrades RNA during RBC maturation. Inhibition prevents breakdown, causing rRNA to clump.
  • Prussian blue staining of bone marrow: ringed sideroblasts

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Management

• 1. Remove Offending Agent / Treat Underlying Cause (First-line):
  • Alcohol cessation: Resolves alcohol-induced mitochondrial toxicity.
  • Drug-induced (e.g., INH): Discontinue or administer Pyridoxine (Vitamin B6) ($50\text{–}100\text{ mg/day}$). c
  • Nutritional copper deficiency: Oral or IV copper supplementation; cease zinc supplements.
  • Congenital (ALAS2 mutation): Trial of high-dose Pyridoxine (Vitamin B6) ($100\text{–}200\text{ mg/day}$) lifelong.
• 2. Etiology-Specific Second-line Therapies:
  • Lead Poisoning:
    • Mild-moderate: Oral Succimer (DMSA).
    • Severe / Encephalopathy: IV Dimercaprol (BAL) followed by IV Calcium disodium EDTA.
  • MDS with Ring Sideroblasts:
    • Luspatercept (erythroid maturation agent) for transfusion-dependent pts with SF3B1 mutation refractory to ESAs.
    • Erythropoiesis-stimulating agents (ESAs) if endogenous EPO $\le 500\text{ mU/mL}$.
• 3. Management of Complications (Iron Overload):
  • Iron Chelation Therapy: Deferasirox (oral) or Deferoxamine (subQ/IV) indicated when ferritin $>1000\text{ ng/mL}$ or in chronic transfusion dependence.
  • Avoid empiric iron supplementation.
  • Phlebotomy: Reserved only for pts with mild congenital forms who achieve normal Hb levels on pyridoxine.