Sideroblastic Anaemia

Synonyms: Refractory anaemia with ringed sideroblasts (RARS)

They are characterized by the presence of abnormal ringed sideroblasts in bone marrow aspirate. According to the WHO classification sideroblastic anaemia shows anaemia, no blasts in the peripheral blood, isolated erythroid dysplasia with <5% blasts and >15% ringed sideroblasts in the bone marrow.¹ The sideroblasts form due to reduced haemoglobin synthesis, resulting in the accumulation of iron within red blood cell precursors.

Cases can rarely be congenital. The most frequent form is X-linked sideroblastic anaemia, caused by mutations of delta-aminolevulinic acid synthase 2 (ALAS2), the enzyme that catalyses the first and regulatory step of haem synthesis in erythroid precursors.² However cases are more usually acquired and sometimes represent a stage in the development of myelodysplastic syndromes.

This accounts for 5-15% of all myelodysplastic syndromes.³ 70% of all patients are aged >50years old.
Hereditary forms of sideroblastic anaemia are X-linked and more common in males.⁴ Cases can be related to ataxia and the condition may not present until the fourth decade or later if mild.⁵

In addition to the myelodysplastic syndromes, sideroblastic anaemia can also occur in other bone marrow diseases including:

• Myeloma
• Polycythaemia rubra vera
• Myelosclerosis
• Leukaemias

Secondary causes include:

• Inflammatory conditions, e.g. rheumatoid arthritis
• Systemic lupus erythematosus
• Chronic infections
• Drug toxicity, e.g. chloramphenicol, cycloserine, isoniazid, linezolid, pyrazinamide
• Chronic alcoholism
• Haemolytic anaemia
• Malabsorption syndromes
• Myxoedema
• Lead poisoning
• Pregnancy

Clinical features are those related to anaemia in general. Symptoms reflect the cytopenias, i.e. anaemia, infection, bruising and haemorrhage.
There are no specific signs or symptoms related to sideroblastic anaemia alone.

Diagnosis is made from bone marrow examination demonstrating the presence of ring sideroblasts with a generalized increase in iron stores.

• A full blood count (FBC) usually shows a moderate anaemia.
• The mean corpuscular volume (MCV) is normal or increased, but can be low.
• High serum iron and transferring saturation also occur.
• The blood film shows a dimorphic population of both normal and hypochromic red blood cells.

General measures

• Treatment is mainly supportive.
• Red cell transfusion is given for symptomatic anaemia.
• Iron chelation with desferrioxamine should be considered after 20-25 units of red cells have been received.⁶
• Avoid alcohol and vitamin C as these increase iron absorption

Pharmacological

• The use of erythropoietin ± granulocyte colony-stimulating factor has been demonstrated to reduce the need for red cell transfusion in some patients with myelodysplastic syndrome but the studies were small.^6,7
• Patients with hereditary sideroblastic anaemia may respond to pyridoxine.^6,8
• Cyclosporin A has been shown to give a response rate (i.e. alteration of disease progression or remission) of 62.5% in patients with myelodysplastic syndromes including sideroblastic anaemia.⁹
• New therapies are emerging, approved by the United States FDA in 2004. There are two DNA methyltransferase inhibitors (azacitidine and decitabine) and an immunomodulatory agent (lenalidomide).¹⁰

Surgical

• Allogenic peripheral stem cell transplantation has been used with success in pyridoxine refractory hereditary sideroblastic anaemia. Few patients are eligible for transplant.^9,11

Median survival is 51 months.¹² Platelet count has recently been shown to be prognostic also.¹³ Transformation to acute leukaemia occurs in 8% of patients. Death from the complications of marrow failure or intercurrent illness determines the percentage of patients who develop leukaemia.