Snapshot A 35-year-old man presents to the clinic for follow-up for treatment of latent tuberculosis. He is a recent immigrant to the United States from Mexico and started taking isoniazid 2 months ago after he was diagnosed with latent tuberculosis at an occupational health visit. Physical examination is notable for decreased sensation to pinprick in his lower extremities. A bone marrow aspirate is obtained and after staining with Prussian blue, the finding in the image is observed. Introduction Overview sideroblastic anemias are a group of inherited and acquired anemias in which iron accumulates in the mitochondria of erythrocyte precursors ringed sideroblasts (iron-laden erythrocytes with Prussian-blue stained mitochondria) seen on bone marrow aspirate Epidemiology incidence rare demographics X-linked recessive type of inherited sideroblastic anemia occurs more commonly in males median age of occurence of primary acquired sideroblastic anemia is 74 years of age risk factors alcoholism vitamin B6 deficiency lead poisoning copper deficiency Pathophysiology pathophysiology mitochondrial pathways in erythrocyte precursors are disrupted, leading to accumulation of iron in the mitochondria excessive iron deposits in erythroblasts form a ring around the nucleus, making a ringed sideroblast heme synthesis is impaired, leading to ↓ heme production and abnormal RBCs (see Heme Metabolism) X-linked sideroblastic anemia mutation in ALAS2 gene which encodes ALA synthase, the first enzyme of the heme synthesis pathway vitamin B6 (pyridoxine) is a necessary cofactor for ALA synthase isoniazid disrupts conversion of vitamin B6 (pyridoxine) to its active cofactor chronic alcohol use impairs vitamin B6 metabolism toxic effects on mitochondrial protein synthesis lead poisoning inhibits several enzymes involved in heme synthesis ALA dehydratase ferrochelatase Genetics inheritance pattern X-linked (inherited sideroblastic anemia) mutations ALAS2 gene encodes for ALA synthase Prognosis highly variable depending on cause anemia due to reversible causes (i.e., alcohol and drugs) do not have long-term sequelae secondary hemochromatosis (from transfusions) and leukemia are major causes of death Presentation Symptoms general symptoms of anemia fatigue weakness dyspnea on exertion lack of coordination (cerebellar symptoms) diarrhea Physical exam growth delay in children ataxia ↓ deep-tendon reflexes incoordination dyspnea muscular weakness Studies Serum labs ↑ serum iron and ferritin ↓ TIBC ↓ or normal MCV Histology peripheral blood smear hypochromic RBCs Pappenheimer bodies in RBCs abnormal basophilic granules of iron low reticulocyte count bone marrow stained with Prussian blue ringed sideroblasts diagnostic hallmark of all sideroblastic anemias Differential Iron deficiency anemia key distinguishing factor ↓ serum iron and ferritin Megaloblastic anemia key distinguishing factor megaloblastic changes seen on peripheral blood smear and bone marrow rather than ringed sideroblasts Treatment Medical pyridoxine (vitamin B6) supplementation