Sideroblastic anemia
Sideroblastic anemia is an anemia caused by defective heme synthesis, in which iron accumulates in the mitochondria of red cell precursors and forms ring sideroblasts visible on bone marrow staining. It can be inherited or acquired from causes such as alcohol, lead, or vitamin B6 deficiency.
Sideroblastic anemia is a group of anemias defined by a common mechanism: the bone marrow cannot properly incorporate iron into heme. Iron enters developing red blood cells but, because protoporphyrin synthesis is impaired, it cannot be built into hemoglobin. The unused iron accumulates in the mitochondria that ring the nucleus of erythroid precursors, producing the diagnostic ring sideroblast seen on bone marrow aspirate with Prussian blue staining.
Causes are divided into congenital and acquired. The classic congenital form is X-linked, caused by a mutation in the ALAS2 gene encoding δ-aminolevulinic acid synthase, the rate-limiting enzyme of heme synthesis. Acquired causes include chronic alcohol use, lead poisoning, copper deficiency, myelodysplastic syndromes, and medications such as isoniazid — which interferes with vitamin B6 (pyridoxine), a required cofactor for ALAS.
Laboratory findings distinguish sideroblastic anemia from other microcytic anemias. Like iron deficiency, it is often microcytic and hypochromic, but the iron studies point the opposite direction: serum iron and ferritin are elevated and total iron-binding capacity is decreased, because the body has plenty of iron it simply cannot use. Reversible causes respond to removing the offending agent, and pyridoxine-responsive forms improve with B6.
The USMLE Step 1 exam tests sideroblastic anemia within hematology, typically asking you to connect a clue — isoniazid therapy, lead exposure, alcohol use, or an X-linked family history — to ring sideroblasts and an iron-overloaded lab profile in a microcytic anemia.
Key takeaways
- Sideroblastic anemia results from defective heme synthesis, trapping iron in the mitochondria of red cell precursors.
- Ring sideroblasts on Prussian blue-stained bone marrow are the hallmark finding.
- Causes include X-linked ALAS2 mutations, alcohol, lead, copper deficiency, myelodysplasia, and isoniazid (via B6 interference).
- Iron studies show high serum iron and ferritin with low TIBC, distinguishing it from iron deficiency anemia.
- USMLE Step 1 questions pair an exposure clue with ring sideroblasts and iron overload in a microcytic anemia.