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Causes and pathophysiology of the sideroblastic anemias

Author
Sylvia S Bottomley, MD
Section Editor
Stanley L Schrier, MD
Deputy Editor
Jennifer S Tirnauer, MD

INTRODUCTION

Sideroblastic anemias are anemias in which ring sideroblasts are present on the bone marrow aspirate smear stained for iron with Prussian blue. Ring sideroblasts are found in diverse circumstances, which underscores a broad spectrum of causes of sideroblastic anemia, both inherited and acquired (table 1). Understanding the causative mechanisms is useful for predicting the disease course and guiding therapy, which differ for the various sideroblastic anemia forms.

This topic review discusses the recognized congenital and acquired causes of the sideroblastic anemias and their pathophysiology. The clinical presentations and diagnostic testing for specific forms of sideroblastic anemia, and our approach to patient management, are presented in detail separately. (See "Sideroblastic anemias: Diagnosis and management".)

CAUSES OF SIDEROBLASTIC ANEMIAS

The conventional classification of the sideroblastic anemias is structured on whether the cause is congenital (inherited) or acquired, followed by listing specific genetic defects or environmental factors (table 1). In searching for the cause it can also be helpful to note whether the anemia is microcytic or normocytic/macrocytic (table 2).

Congenital sideroblastic anemias — Congenital sideroblastic anemias are caused by a germline mutation (or other genetic alteration) in a nuclear or mitochondrial gene (or genes). For a number of forms, underlying defects have been established at the molecular level, as illustrated in the diagram (figure 1). However, approximately one-third of cases do not have an identifiable genetic defect as of yet [1-3]. The causative defects for these patients are actively being sought in research laboratories.

The congenital sideroblastic anemias can be subdivided into syndromic and non-syndromic forms (table 1), by their mode of inheritance (X-linked, autosomal recessive, or mitochondrial) or according to red blood cell size (microcytic or normocytic-to-macrocytic) (table 2). The majority appear as non-syndromic, with isolated anemia and ring sideroblasts in the bone marrow. The syndromic forms, which affect other organ systems, are very uncommon.

                                  

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Literature review current through: Jul 2017. | This topic last updated: Jun 28, 2017.
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