What is the management approach for sideroblastic anaemia?

Management of Sideroblastic Anemia

The management of sideroblastic anemia must be tailored to the specific genetic defect causing the condition, with treatment approaches including pyridoxine supplementation for ALAS2 defects, hematopoietic stem cell transplantation for severe cases, and management of iron overload. 1

Diagnostic Approach

Before initiating treatment, proper diagnosis is essential:

• Evaluate for ring sideroblasts in bone marrow aspirate 2
• Check iron parameters (ferritin, transferrin saturation) to detect iron loading 1
• Consider genetic testing based on clinical presentation and family history 2
• Rule out acquired causes (medications, alcohol, lead poisoning, myelodysplastic syndromes) 3

Treatment Based on Genetic Subtype

X-linked Sideroblastic Anemia (XLSA) due to ALAS2 defects

• Initial treatment with pharmacologic doses of pyridoxine (50-200 mg/day) 1
• Higher doses (up to 300 mg/day) may be considered in overweight, active, or elderly patients 1
• For pyridoxine-responsive cases, continue lifelong supplementation with maintenance dose of 10-100 mg daily 1
• Monitor for neurotoxicity with excessive pyridoxine doses 1
• Manage iron overload preferably with phlebotomies when possible 1

Sideroblastic Anemia due to SLC25A38 defects

• Hematopoietic stem cell transplantation (HSCT) is the only curative option and is recommended 1
• Symptomatic treatment includes erythrocyte transfusions and iron chelation therapy 1

Sideroblastic Anemia due to STEAP3 defects

• Treat with erythrocyte transfusions in combination with erythropoietin (EPO) 1
• Address systemic iron loading with iron chelation therapy 1

X-linked Sideroblastic Anemia with Ataxia (XLSA/A) due to ABCB7 defects

• Anemia is typically mild and treatment is generally not indicated 1
• Focus on management of neurological manifestations 1

Sideroblastic Anemia due to GLRX5 defects

• Monitor iron status and complications of iron overload 1
• Treat iron loading with chelation therapy 1
• Manage severe anemia with blood transfusions 1

Management of Iron Overload

• Regular monitoring of iron parameters (ferritin, TSAT) 1
• Check liver enzymes and signs of liver fibrosis or hepatocellular carcinoma 1
• Phlebotomy is preferred when tolerated 1
• Iron chelation therapy when phlebotomy is not tolerated or contraindicated 1, 2
• Consider MRI of the liver to assess iron loading, as normal serum ferritin may not exclude liver iron accumulation 1

Management of Acquired Sideroblastic Anemia

• For myelodysplastic syndrome (MDS) with ring sideroblasts:
  • Erythroid maturation agents like luspatercept may be beneficial 2
  • Pyridoxine has limited efficacy in unselected AISA populations (only 1.4% respond to monotherapy) 4
• For reversible causes (alcohol, drugs, toxins):
  • Remove the offending agent 3

Family Screening and Genetic Counseling

• Genetic counseling based on inheritance pattern of the specific defect 1
• For XLSA (ALAS2 defects):
  • Screen brothers who may be affected 1
  • Screen mother, sisters, and daughters for carriership 1
  • Female carriers may develop XLSA phenotype later in life 1

Important Caveats and Pitfalls

• Pyridoxine therapy should be reserved for patients with known or suspected pyridoxine-responsive mutations (primarily XLSA due to ALAS2 defects), as it is largely ineffective in acquired sideroblastic anemia 4
• Excessive pyridoxine doses can cause peripheral neuropathy (reported in 2.3% of treated patients) 4
• Iron overload can occur even without transfusion dependency due to ineffective erythropoiesis 5
• Regular monitoring for complications of iron overload is essential even in patients with mild anemia 1, 5