Makindo Medical Notes

Related Subjects: | Sideroblastic Anaemia

About

• Rare form of anaemia characterized by ringed sideroblasts in the bone marrow.
• Sideroblasts are erythroblasts (immature red blood cells) that contain iron-loaded mitochondria, which have failed to incorporate iron into haemoglobin.

Aetiology

• These ringed sideroblasts are stained with Prussian Blue and contain iron granules surrounding approximately one-third of the nucleus. Erythrocytes do not normally contain a nucleus.
• The final stage of haem synthesis is the incorporation of iron into protoporphyrin IX to form haem.
• Alcohol can cause sideroblastic anaemia by interfering with the availability of Pyridoxal 5' phosphate (vitamin B6), a cofactor required by aminolevulinic acid synthase (ALAS), which is essential for haem synthesis.
• Iron is used in haemopoiesis. Iron is stored as Fe³⁺(ferric form) but must be reduced to Fe²⁺(ferrous form) to be incorporated into haem.
• This reduction is carried out by ferrochelatase using electrons provided by the mitochondrial electron transport chain.
• An inability to properly utilize iron can lead to iron overload, and patients may exhibit mild hepatosplenomegaly (enlarged liver and spleen).

Clinical Presentation

• Anaemia, presenting as fatigue and weakness.
• May include flow murmurs (due to increased cardiac output compensating for anaemia).
• Symptoms depend on the underlying cause of the sideroblastic anaemia.
• A thorough history is important, including inquiries about drug use, alcohol consumption, and family history.

Causes of Sideroblastic Anaemia

• Myelodysplastic syndromes (MDS), which can lead to defective erythropoiesis.
• Toxins, including lead and alcohol, which impair haem synthesis.
• Certain drugs, such as isoniazid and pyrazinamide, which interfere with vitamin B6 metabolism.
• Hereditary sideroblastic anaemia, often linked to mutations in genes like ALAS2 (X-linked) or deficiencies in ferrochelatase.

Investigations

• A dimorphic blood film, with a mix of microcytic and normocytic red blood cells.
• Hypochromic, microcytic anaemia is typical, although some normocytic cells may be present.
• Bone marrow biopsy reveals ringed sideroblasts, where iron granules are deposited in a ring around the erythroblast nucleus.
• Iron studies may show increased serum iron and ferritin levels, indicating iron overload.

Management

• Identify and treat the underlying cause, such as cessation of alcohol consumption or discontinuation of causative drugs.
• Bone marrow biopsy is often required for definitive diagnosis.
• Some patients may respond to treatment with pyridoxine (vitamin B6), particularly if the cause is related to ALAS2 mutations.
• Other patients may require supportive care, including blood transfusions to manage anaemia.
• In severe cases, erythropoietin (EPO) therapy or hematopoietic stem cell transplantation may be considered.