Contents
Introduction
Anaemia that results from abnormal utilization of iron during erythropoiesis.

Aetiology
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

Pathophysiology
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:
- Type 1 sideroblasts: < 5 siderotic granules in cytoplasm
- Type 2 sideroblasts: ≥ 5 siderotic granules (no perinuclear distribution)
- 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
XLSA:
- 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
Complications:
- Cardiovascular complications
- Hepatic damage
- Kidney failure
Diagnosis
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

Iron studies:
- ↑ Serum iron
- ↑ Ferritin
- ↓ TIBC
Management
Manage iron overload:
- Therapeutic phlebotomy “bloodletting”
- Deferoxamine (iron-chelating agent)
Severe cases:
- Bone marrow or liver transplantation