How is sideroblastic anemia managed?

Management of Sideroblastic Anemia

Initial Treatment Based on Genetic Subtype

For X-linked sideroblastic anemia (XLSA) due to ALAS2 defects, start with pyridoxine (vitamin B6) 50-200 mg daily, which improves anemia and iron overload in all responsive patients. 1, 2

Pyridoxine-Responsive XLSA (ALAS2 Defects)

• Begin with oral pyridoxine 50-200 mg per day as initial therapy 1, 2
• Once response is achieved, reduce to a lifelong maintenance dose of 10-100 mg daily to avoid neurotoxicity from excessive dosing 1, 2
• Critical pitfall: Do not label patients as pyridoxine-refractory until iron stores are normalized, as iron overload itself compromises mitochondrial function and heme biosynthesis 1
• Most patients show improvement in both anemia and iron parameters with pyridoxine therapy 1

Severe Autosomal Recessive Forms (SLC25A38 Defects)

• Hematopoietic stem cell transplantation (HSCT) is the only curative option and should be considered early 2
• Provide symptomatic treatment with red blood cell transfusions until definitive therapy can be implemented 2
• Implement iron chelation therapy to manage transfusion-related iron overload 2

Other Rare Genetic Forms

• For STEAP3 defects: treat with erythrocyte transfusions combined with erythropoietin (EPO), and manage systemic iron loading with chelation therapy 2
• For ABCB7 defects: supportive care as these patients typically have mild microcytic anemia with cerebellar ataxia 1

Management of Iron Overload

Phlebotomy is the preferred method for managing iron overload when tolerated, as most XLSA patients have mild anemia that actually improves with iron removal. 1, 2

• Hemoglobin typically increases rather than decreases after reversal of iron overload by phlebotomy in XLSA patients 1
• Use iron chelation therapy only when phlebotomy is not tolerated or causes decreasing hemoglobin 2
• Monitor iron parameters regularly (ferritin, transferrin saturation) 2
• Check liver enzymes and assess for signs of liver fibrosis or hepatocellular carcinoma 2
• Consider MRI of the liver to assess iron loading in patients with significant iron accumulation 2

Acquired Sideroblastic Anemia (MDS with Ring Sideroblasts)

For myelodysplastic syndrome with ring sideroblasts (MDS-RS), especially with SF3B1 mutation, luspatercept is now approved and achieves erythroid response rates up to 63% with transfusion independence in 38% of patients. 2

• Luspatercept represents a major advance for transfusion-dependent MDS-RS patients 2
• Red blood cell transfusions remain the mainstay for symptomatic anemia across all subtypes 2
• Recent case reports suggest luspatercept may also benefit select congenital cases (ALAS2, SLC25A38) who become unresponsive to vitamin B6 3

Reversible Acquired Causes

• For alcohol-related or nutritional pyridoxine deficiency: vitamin B6 supplementation can normalize blood counts within one month 4
• Always evaluate for reversible causes including alcohol use, medications, copper deficiency, and nutritional deficiencies before attributing to genetic causes 5

Genetic Testing and Family Screening

• For suspected XLSA: perform ALAS2 gene testing 2
• Screen brothers who may be affected and screen mother, sisters, and daughters for carriership in X-linked cases 2
• For children with severe microcytic sideroblastic anemia: consider SLC25A38 gene testing 2
• Provide genetic counseling based on the inheritance pattern of the specific defect 2
• Refer patients with rare genetic forms to a clinical geneticist 2

Monitoring Strategy

• Monitor hemoglobin and iron parameters (ferritin, transferrin saturation) regularly 2
• Assess liver function and screen for hepatic complications in patients with iron overload 2
• For pyridoxine-treated patients, maintain the lowest effective dose to prevent neurotoxicity while controlling anemia 1