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Sideroblastic Anemias


Gloria F. Gerber

, MD, Johns Hopkins School of Medicine, Division of Hematology

Reviewed/Revised Jun 2023
Topic Resources

Sideroblastic anemias are a diverse group of anemias characterized by the presence of increased serum iron, ferritin, and transferrin saturation as well as ringed sideroblasts (erythroblasts with perinuclear iron-engorged mitochondria). Symptoms are those of anemia and include fatigue and lethargy. Diagnosis is with complete blood count, reticulocyte count, and peripheral blood smear as well as iron studies and bone marrow examination. Treatment requires stopping causative substances and giving vitamin supplements and erythropoietin.

Sideroblastic anemias may be

  • Acquired

  • Congenital

Congenital sideroblastic anemia is caused by one of numerous X-linked or autosomal mutations and is usually a microcytic, hypochromic anemia but may be normocytic.

Sideroblastic anemias are iron-utilization anemias, which are characterized by inadequate mitochondrial utilization of iron due to impaired heme synthesis despite the presence of adequate or increased amounts of iron. Sideroblastic anemias are sometimes characterized by the presence of polychromatophilia (indicative of an increased number of reticulocytes) and stippled red blood cells (siderocytes) containing iron-laden granules (Pappenheimer bodies).

In both acquired and congenital sideroblastic anemia, heme synthesis is impaired due to the inability to incorporate iron into protoporphyrin IX, leading to the formation of ringed sideroblasts.

Acquired sideroblastic anemia

Most often, acquired sideroblastic anemias are part of a

Somatic mutations in genes involved in RNA splicing, most frequently SF3B1 (splicing factor 3b subunit 1), commonly occur. Acquired sideroblastic anemia occurs in adulthood.

Less common causes include

  • Deficiency of vitamin B6 (pyridoxine) or copper (possibly caused by zinc ingestion, which prevents absorption of copper in the gastrointestinal tract)

  • Medications (eg, chloramphenicol, cycloserine, isoniazid, linezolid, pyrazinamide)

  • Toxins (including ethanol and lead)

Deficient reticulocyte production, intramedullary death of red blood cells (RBCs), and bone marrow erythroid hyperplasia (and dysplasia) occur. Although hypochromic RBCs are produced, other RBCs may be large, producing normocytic or macrocytic indices; if so, variation in RBC size (dimorphism) usually produces a high RBC distribution width (RDW).

Congenital sideroblastic anemia

Inherited forms of sideroblastic anemia are less common than acquired forms and usually occur in infancy or early childhood. The most common congenital sideroblastic anemia is an X-linked X-Linked Dominant Genetic disorders determined by a single gene (Mendelian disorders) are easiest to analyze and the most well understood. If expression of a trait requires only one copy of a gene (one allele)... read more form caused by a germline mutation in ALAS2 (5'-aminolevulinate synthase 2), a gene involved in heme biosynthesis. Vitamin B6 (pyridoxine) is an essential cofactor for the enzyme produced by ALAS2, thus patients may respond to pyridoxine supplementation.

Numerous other X-linked, autosomal and mitochondrial forms have been identified with mutations in genes involved in heme synthesis or other mitochondrial enzymatic pathways (1 General reference Sideroblastic anemias are a diverse group of anemias characterized by the presence of increased serum iron, ferritin, and transferrin saturation as well as ringed sideroblasts (erythroblasts... read more General reference ).

RBCs are usually microcytic and hypochromic, but this is not always the case.

General reference

  • 1. Ducamp S, Fleming MD: The molecular genetics of sideroblastic anemia. Blood 133:59–69, 2019. doi: 10.1182/blood-2018-08-815951

Diagnosis of Sideroblastic Anemias

  • Complete blood count (CBC), reticulocyte count, and peripheral blood smear

  • Iron studies (serum iron, serum ferritin, and transferrin saturation)

  • Bone marrow examination

  • Genetic testing for a suspected inherited or acquired mutation

Sideroblastic anemia is suspected in patients with microcytic anemia or a high RDW anemia, particularly with increased serum iron, serum ferritin, and transferrin saturation (see Iron Deficiency Anemia Iron Deficiency Anemia Iron deficiency is the most common cause of anemia and usually results from blood loss; malabsorption, such as occurs in celiac disease, is a much less common cause. Symptoms are usually nonspecific... read more Iron Deficiency Anemia ).

Bone marrow examination is necessary and reveals erythroid hyperplasia. Iron staining reveals the pathognomonic iron-engorged perinuclear mitochondria in developing RBCs (ringed sideroblasts). Other features of myelodysplastic syndrome Myelodysplasia and Iron-Transport Deficiency Anemia In myelodysplastic syndrome, anemia is commonly prominent. The anemia is usually normocytic or macrocytic, and a dimorphic (large and small) population of circulating cells can be present. ... read more , such as cytopenias and dysplasia, may be evident.

Serum lead is measured if sideroblastic anemia has an unknown cause.

Treatment of Sideroblastic Anemias

  • Stopping causative substances

  • Vitamin or mineral supplementation

  • Recombinant erythropoietin (EPO)

Elimination of a toxin or medication (especially alcohol or zinc ingestion), or mineral/vitamin supplementation (copper or pyridoxine) can lead to recovery.

X-linked sideroblastic anemia may respond to pyridoxine 50 mg orally 3 times a day, but usually incompletely.

Treating iron overload with chelation or phlebotomy as tolerated helps to prevent end organ damage. Management of severe anemia is supportive with transfusions. In young patients with congenital cases who are transfusion dependent, allogeneic bone marrow transplant should be considered.

Treatment reference

Key Points

  • Sideroblastic anemia can be acquired or congenital.

  • Ringed sideroblasts on a bone marrow biopsy are pathognomic.

  • Anemia is usually microcytic in congenital sideroblastic anemia and macrocytic in acquired sideroblastic anemia.

  • Serum iron, ferritin, and transferrin are typically increased.

  • Treat the underlying disorder and consider pyridoxine in congenital cases or recombinant erythropoietin in acquired cases.

Drugs Mentioned In This Article

Drug Name Select Trade
AK-Chlor, Chloromycetin, Chloroptic, Chloroptic S.O.P., Ocu-Chlor
Zyvox, Zyvox Powder, Zyvox Solution
No brand name available
B-Natal, Neuro-K-500
No brand name available
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