Understanding Sideroblastic Anemia: An Overview of Genetics, Epidemiology, Pathophysiology and Current Therapeutic Options

Abstract

Sideroblastic anemia (SA) consists of a group of inherited and acquired anemias of ineffective erythropoiesis characterized by the accumulation of ring sideroblasts in the bone marrow due to disrupted heme biosynthesis. Congenital sideroblastic anemia (CSA) is rare and has three modes of inheritance: X-linked (XLSA), autosomal recessive (ARCSA), and maternal. Acquired SA is more common and can be a result of myelodysplastic syndromes (MDS) or other, generally reversible causes. The diagnostic approach to SA includes a work-up for reversible causes and genetic testing for CSA based on clinical suspicion, family history and genetic pedigree. The treatment of SA depends on the underlying etiology but remains primarily supportive with vitamin B6 supplementation for select cases of XLSA, thiamine for thiamine-responsive megaloblastic anemia subtype, red blood cell transfusions for symptomatic patients and iron chelation therapy for iron overload. The management of anemia in MDS subtypes with ring sideroblasts remains unique and includes the recently approved erythroid maturation agent, Luspatercept. Although there is currently no curative therapy for CSA, anecdotal reports of hematopoietic stem cell transplant demonstrate remissions in selective, non-syndromic cases. This review summarizes the genetics, pathophysiology, diagnosis and treatment of SA for general practitioners and clinical hematologists.

Keywords:

• ring sideroblasts
• heme biosynthesis
• congenital sideroblastic anemia
• acquired sideroblastic anemia
• vitamin B6
• iron chelation

Acknowledgments

We acknowledge Dr. Julia T Geyer from the Division of Hematopathology at WCM for providing the high-resolution images of peripheral blood and bone marrow specimens. We also acknowledge Biorender.com for providing us the platform to design Figure 3.

Disclosure

Dr Maria T DeSancho participated in advisory boards for Apellis Pharamceuticals, Bio Product Laboratory, and Sanofi-Genzyme, outside the submitted work. The authors report no other conflicts of interest related to this work.