Sideroblastic Anemia: A type of blood disorder characterized by an accumulation of iron in red blood cells (RBCs), leading to immature and dysfunctional RBCs.
Mechanism: RBCs are unable to incorporate iron into hemoglobin, impairing their ability to transport oxygen.
Hemoglobin and Heme Synthesis
Hemoglobin: Composed of hemes and globins, responsible for carrying oxygen.
Globin Subunits: Typically two alpha and two beta, each with a heme group.
Heme: Large molecule made of four pyrrole subunits forming a porphyrin ring, containing ionically bonded iron (Fe2+).
Oxygen Binding: Each hemoglobin can carry four oxygen molecules.
Heme Synthesis: Involves mitochondria and cytosol and multiple enzymes.
Begins in mitochondria: Succinyl-CoA + Glycine -> Delta-aminolevulinic acid (ALA) via Delta ALA synthase, requiring Vitamin B6.
In cytosol: Delta-ALA -> Porphobilinogen (PBG) via Delta-ALA dehydratase.
Condensation: Four PBG -> Hydroxymethylbilane aided by Porphobilinogen deaminase.
Further transformations: Hydroxymethylbilane -> Uroporphyrinogen III -> Coproporphyrinogen III in mitochondria.
Iron incorporation: Iron added to Protoporphyrin IX by ferrochelatase.
Pathophysiology of Sideroblastic Anemia
Defective Protoporphyrin Synthesis: Leads to impaired iron incorporation to form heme.
Types:
Congenital: Often X-linked, affecting mostly males due to ALAS2 gene mutations, impairing delta ALA synthase.
Acquired:
Excessive alcohol use causing mitochondrial damage.
Pyridoxine (Vitamin B6) deficiency.
Lead poisoning, inhibiting crucial enzymes like Delta-ALA dehydratase and ferrochelatase.
Characteristic Features:
Basophilic stippling in RBCs due to ribosome accumulation.
Ringed sideroblasts in bone marrow.
Clinical Presentation and Diagnosis
Symptoms: Fatigue, potential heart disease, liver damage, enlarged spleen, kidney failure, and diarrhea due to iron overload.
Diagnosis:
Clinical Evaluation: Similar to hemochromatosis.
Laboratory Findings:
Complete blood count: Normal or low mean corpuscular volume.
Peripheral blood smear: Basophilic stippling and Pappenheimer bodies.
Iron studies: High serum iron, increased ferritin levels, decreased total iron binding capacity.
Treatment
Removal of Toxins: Important in acquired cases (e.g., alcohol, lead).
Nutritional Support: Administration of pyridoxine, thiamine, and folic acid.
Iron Overload Management:
Therapeutic phlebotomy or chelation therapy (deferoxamine).
Severe Cases: May require bone marrow or liver transplant.
Recap
Cause: Either congenital abnormalities or acquired conditions lead to a failure in iron incorporation for heme production.
Impact: Iron overload damages organs, and lack of functional heme results in anemia and fatigue.
Management: Focus on toxin removal and vitamin supplementation to improve heme synthesis.