Sideroblastic Anaemia
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Direct answer
Sideroblastic anaemia is a group of disorders in which iron enters the mitochondria of erythroid precursors but cannot be incorporated into haem, so iron accumulates around the nucleus as ring sideroblasts on a bone marrow iron stain. Common acquired causes include alcohol, lead poisoning and isoniazid, while the inherited X-linked form results from ALAS2 mutations. Its key therapeutic distinction is pyridoxine response, which occurs in some isoniazid and inherited cases and is usually absent in myelodysplasia-associated disease.
What you must remember
- Ring sideroblasts: erythroblasts with iron granules encircling the nucleus on Prussian blue staining; WHO criteria use 15 percent or more of erythroid precursors, with a lower threshold when an SF3B1 mutation is present.
- Lead toxicity: inhibits ferrochelatase and ALA dehydratase, producing basophilic stippling and raised urinary delta-aminolaevulinic acid; severe cases need chelation.
- Isoniazid: depletes pyridoxal phosphate, so pyridoxine is co-prescribed in patients at risk such as those with malnutrition, alcohol use or diabetes.
- Alcohol: a common reversible cause, with ring sideroblasts that often regress after abstinence.
- Inherited X-linked form: ALAS2 mutations cause a microcytic, hypochromic anaemia in males, and some cases respond to pyridoxine.
- Mitochondrial causes: Pearson syndrome, with mitochondrial DNA deletion and exocrine pancreatic dysfunction, is a rare syndromic cause.
A worked case: microcytosis on a tuberculosis regimen
A 45-year-old man on a standard tuberculosis regimen including isoniazid develops tingling in his feet and a microcytic anaemia.
- Read the iron studies: Serum iron and ferritin are high and the MCV is low, a combination that argues against iron deficiency. A marrow iron stain shows ring sideroblasts, and the peripheral smear shows a dimorphic picture.
- Identify the likely drug: Isoniazid is the likely cause, so a trial of pyridoxine is started with the tuberculosis team, and the anaemia and neuropathy are monitored.
- Keep tuberculosis treatment: Isoniazid is usually continued with pyridoxine cover rather than stopped, since effective tuberculosis treatment is the priority. The decision is made with the programme team.
- Contrast myelodysplasia: A 62-year-old with macrocytic anaemia, pancytopenia and ring sideroblasts on marrow, but no drug or alcohol history, has myelodysplasia with ring sideroblasts. Pyridoxine is unlikely to help, and management shifts to transfusion and disease-directed therapy under haematology.
- Confirm with marrow studies: A bone marrow examination with iron staining and molecular testing is usually needed to tell the two apart.
Where the examiner sets the trap
A few traps recur with this anaemia.
- Trap: reading a microcytic anaemia with high serum iron and ferritin as iron deficiency Correct: iron is accumulating in the wrong place rather than being deficient.
- Trap: assuming pyridoxine always cures Correct: it helps isoniazid and some inherited cases but rarely myelodysplasia.
- Trap: missing lead in a child with pica or an adult with occupational exposure Correct: think of lead, since basophilic stippling and raised urinary delta-aminolaevulinic acid point to it.
- Trap: ignoring preventive pyridoxine with isoniazid Correct: pyridoxine is co-prescribed with isoniazid in those at risk, so an anaemia that develops on treatment reveals a missed preventive step.
Frequently asked questions
What are ring sideroblasts?
Ring sideroblasts are erythroblasts whose iron granules encircle the nucleus on Prussian blue staining, reflecting iron trapped in mitochondria. They are seen in sideroblastic anaemia and in myelodysplastic syndrome with ring sideroblasts, so the context decides the interpretation.
Which drug causes sideroblastic anaemia and responds to pyridoxine?
Isoniazid causes sideroblastic change by depleting pyridoxal phosphate, and pyridoxine supplementation often reverses the anaemia. Pyridoxine is therefore given with isoniazid to patients at risk, such as those with malnutrition or alcohol use.
How does lead cause sideroblastic anaemia?
Lead inhibits enzymes of haem synthesis including ALA dehydratase and ferrochelatase, so protoporphyrin accumulates and iron is not incorporated into haem. Basophilic stippling and raised urinary delta-aminolaevulinic acid support the diagnosis.
Which inherited form of sideroblastic anaemia is X-linked?
X-linked sideroblastic anaemia results from ALAS2 mutations, affecting the erythroid-specific first enzyme of haem synthesis, and causes microcytic anaemia in males. Some cases respond to pyridoxine, so a trial is worthwhile in suspected inherited disease.