Sideroblastic Anemia

Sideroblastic anaemia is a group of disorders with ineffective erythropoiesis and ring sideroblasts in the marrow (iron laden mitochondria around the nucleus).

• Congenital: X linked ALAS2 mutations (commonest, pyridoxine responsive in some), SLC25A38, GLRX5, ABCB7 (with ataxia), mitochondrial deletions (Pearson syndrome), YARS2, PUS1.
• Acquired clonal: MDS with ring sideroblasts (SF3B1 mutation), refractory anaemia with ring sideroblasts.
• Acquired reversible: alcohol, lead poisoning, copper deficiency, zinc excess, drugs (isoniazid, linezolid, chloramphenicol, cycloserine), pyridoxine deficiency.
• Complications: iron overload even without transfusion, cardiac and hepatic dysfunction, diabetes.

• Pallor, fatigue, dyspnoea, hepatosplenomegaly.
• Hypochromic microcytic (congenital) or dimorphic/macrocytic (acquired) red cells.
• Iron overload signs: skin bronzing, diabetes, heart failure.
• Neurological signs (ataxia) in ABCB7; lead exposure features (abdominal pain, neuropathy, basophilic stippling).

• Blood film: dimorphic population, basophilic stippling, Pappenheimer bodies; raised ferritin and transferrin saturation.
• Bone marrow: Prussian blue stain with 15% or more ring sideroblasts (over 5 iron granules encircling at least one third of the nucleus); cytogenetics.
• Gene testing (ALAS2, SF3B1 and panel), lead level, copper, caeruloplasmin, zinc, alcohol history, drug review.
• Liver iron by MRI T2*, glucose, cardiac assessment.

• Remove cause: stop alcohol, isoniazid, linezolid; chelate lead (succimer 10 mg/kg three times daily for 5 days then twice daily for 14 days); replace copper.
• Pyridoxine 50 to 200 mg daily for 3 months (trial; response in ALAS2 and some acquired forms), with folic acid 5 mg daily.
• Transfusion for symptomatic anaemia; erythropoiesis stimulating agents (epoetin 450 units/kg/week) in lower risk MDS RS; luspatercept 1 to 1.75 mg/kg SC every 3 weeks in MDS with ring sideroblasts and transfusion dependence.
• Iron chelation (deferasirox 20 to 30 mg/kg daily) or phlebotomy for non transfused congenital disease with iron overload.
• Allogeneic transplant for severe congenital disease or high risk MDS.
• Monitor ferritin, liver and cardiac iron, glucose; follow clonal evolution in MDS.