Sideroblastic anemias
Sideroblastic anemias are disorders of defective mitochondrial heme synthesis in which iron accumulates around the erythroblast nucleus, producing ring sideroblasts on marrow Prussian blue stain and, unlike iron deficiency, iron overload rather than iron depletion. Causes are hereditary, clonal (myelodysplastic syndrome with ring sideroblasts), or reversible acquired (alcohol, lead, isoniazid/B6 deficiency, copper deficiency, zinc excess, chloramphenicol), and management centers on identifying and reversing the cause, a pyridoxine trial, and treating iron overload.
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What this article covers
- Overview
Definition: sideroblastic anemias are a group of disorders sharing a final common defect in mitochondrial heme synthesis within developing erythroblasts, so that iron delivered to the mitochondrion…
- Epidemiology
Acquired forms are more common than hereditary forms in adults, dominated by reactive causes (alcohol, drugs, nutrient deficiency or excess) and by ring sideroblasts as a clonal MDS feature.
- Risk factors
Chronic heavy alcohol use: the most common reactive cause in adults.
- Pathophysiology
Heme synthesis begins and ends in the mitochondrion: the pathway starts with pyridoxal-phosphate-dependent condensation of glycine and succinyl-CoA and finishes with insertion of iron into…
- Clinical features
Nonspecific anemia symptoms: fatigue, dyspnea on exertion, and pallor, developing gradually and often mild until anemia is advanced.
- Differential diagnosis
Iron deficiency anemia: also microcytic with a high RDW, but ferritin and transferrin saturation are low and TIBC is high, the opposite iron pattern from sideroblastic anemia (iron deficiency anemia).
- Diagnosis
The diagnosis is established by finding ring sideroblasts (erythroid precursors with perinuclear iron granules encircling at least a third of the nuclear circumference) on Prussian blue iron stain of…
- Management
Identify and remove or treat the reversible cause first, because most acquired sideroblastic anemia improves or resolves once the offending exposure is corrected.
- Complications
Secondary iron overload (hemosiderosis): cardiac arrhythmia and dysfunction, hepatic fibrosis, and endocrinopathy from chronic tissue iron deposition, worsened by any red cell transfusion.
- Prognosis
Reversible, reactive causes carry a good prognosis once the exposure or deficiency is corrected, with hematologic recovery over weeks.
- Prevention
Co-prescribe pyridoxine with isoniazid in patients at increased risk (pregnancy, malnutrition, alcohol use disorder, diabetes, HIV), 25 to 50 mg PO once daily for the full duration of isoniazid therapy.
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- Myelodysplastic syndromes
Myelodysplastic syndromes are clonal stem cell disorders producing ineffective hematopoiesis: a dysplastic, usually hypercellular bone marrow with peripheral cytopenias and a variable risk of transformation to acute myeloid leukemia. Diagnosis requires bone marrow biopsy showing dysplasia after excluding reversible mimics, risk is stratified with the IPSS-R, and treatment ranges from supportive transfusions and lenalidomide in lower-risk disease to hypomethylating agents and allogeneic transplant, the only cure, in higher-risk disease.
- Iron deficiency anemia
Iron deficiency anemia is the most common anemia worldwide, a microcytic hypochromic anemia driven by chronic blood loss, poor intake or malabsorption, or increased iron demand. A ferritin below 15 ng/mL confirms depleted iron stores, and confirmed disease in men or postmenopausal women mandates bidirectional endoscopy to find an occult gastrointestinal source before treating with oral or intravenous iron.
- Alpha-thalassemia
Alpha-thalassemia is an inherited microcytic anemia caused by deletions of one or more of the four alpha-globin genes, ranging from a silent carrier state to fatal hemoglobin Barts hydrops fetalis, and it is distinguished from iron deficiency by a normal or elevated RBC count, a normal RDW, and normal iron studies. Diagnosis of the trait requires excluding iron deficiency and often direct globin gene testing because hemoglobin electrophoresis is typically normal, while hemoglobin H disease shows a detectable beta-globin tetramer and HbH inclusions on supravital stain.
- Beta-thalassemia
Beta-thalassemia is an inherited hemoglobinopathy caused by point mutations that reduce or abolish beta-globin chain synthesis, producing a spectrum from asymptomatic trait to transfusion-dependent thalassemia major (Cooley anemia) with ineffective erythropoiesis, marrow expansion, and hepatosplenomegaly. Diagnosis rests on hemoglobin electrophoresis showing elevated HbA2 and HbF, and management of major disease centers on chronic transfusion paired with iron chelation, since transfusional iron overload is the leading cause of death.
- Anemia of chronic disease
Anemia of chronic disease, also called anemia of inflammation, is a normocytic normochromic anemia driven by hepcidin-mediated iron sequestration and cytokine blunting of erythropoiesis in patients with chronic infection, autoimmune disease, malignancy, or kidney disease. The iron-study pattern of low serum iron, low total iron-binding capacity, and normal-to-high ferritin distinguishes it from iron deficiency, and management centers on treating the underlying disease rather than iron supplementation.
- Lead poisoning
Lead poisoning is chronic accumulation of inorganic lead, most often from lead paint dust in pre-1978 housing in children or occupational inhalation in adults, that inhibits heme synthesis and injures the developing brain and kidneys. Diagnosis rests on a venous blood lead level. Management is graded by that level: mandatory source removal at every threshold, oral succimer for 45 to 69 mcg/dL, and combined dimercaprol plus edetate calcium disodium for encephalopathy or levels of 70 mcg/dL or higher.