Sideroblastic anemia is a group of hematological disorders mainly characterized by an interference in heme synthesis. It may be due to genetic defects in heme synthesis or acquired impairment of the production of heme, ultimately leading to iron overload and anemia.
Sideroblastic anemia, as a result of underutilization of iron, is characterized by increased serum ferritin and saturation of transferrin.
Signs and symptoms of sideroblastic anemia result primarily from the reduced hemoglobin production and iron overload. These features vary in severity and include fatigue, palpitations, pallor, dyspnea, and hepatosplenomegaly. Chronic sideroblastic anemia may also lead to acute leukaemia in about 10% of the cases.
Iron overload may also cause long-term organ damage caused by the resulting hemochromatosis.
Entire Body System
There are two forms of sideroblastic anemia, i.e., inherited and acquired sideroblastic anemia. [ncbi.nlm.nih.gov]
Sideroblastic anemia, or sideroachrestic anemia, is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes).  In sideroblastic anemia, the body has iron available but cannot incorporate [en.wikipedia.org]
- Refractory Anemia
The chromosomal pattern of the patient was varied, and was accompanied by the development of refractory anemia with an excess of blasts from refractory anemia with ringed sideroblast 4 months after presentation. [ncbi.nlm.nih.gov]
A 3-month-old boy presented with decreased appetite, fatigue, and a nosebleed. [ashpublications.org]
The signs and symptoms of this condition may include fatigue, breathing difficulties, weakness, and enlargement of the liver or spleen. [rarediseases.info.nih.gov]
Moderate to severe anemia with fatigue, dizziness, and dyspnea should prompt an evaluation for SA. Symptoms of anemia, including fatigue, dizziness, and dyspnea ( 3 )[ A ] Alcohol or drug ... Treatment is largely supportive ( 2 )[ A ]. [5minuteconsult.com]
Blood 2017 129:2710; doi: A 3-month-old boy presented with decreased appetite, fatigue, and a nosebleed. [bloodjournal.org]
Case 1 A 1.5 year-old-male child presented in the outpatient department of hematology with complaints of pallor since birth. [ijpmonline.org]
• Physical findings may include pallor, tachycardia, hepatosplenomegaly, S3, JVD, and rales. ASSESSMENT FINDINGS Sideroblastic anemias usually produce nonspecific clinical effects that can exist for several years before being identified. [encyclopedia.lubopitko-bg.com]
History Part I: Pattern Recognition: Typical symptoms of anemia, if severe enough, such as fatigue, light-headedness, pallor, decreased cardiac endurance. [clinicaladvisor.com]
Most affected individuals have a shortage of red blood cells ( anemia ), which can cause pale skin (pallor), weakness, and fatigue. Some of these individuals also have low numbers of white blood cells (neutropenia) and platelets (thrombocytopenia). [ghr.nlm.nih.gov]
Physical findings: • Poor growth/failure to thrive; • Hepatosplenomegaly (enlarged liver and spleen); and • Pallor (pale skin). [secure.ssa.gov]
- Congestive Heart Failure
Complications Possible complications of sideroblastic anemia include: Congestive heart failure Diabetes mellitus Enlargement of the liver and spleen Formation of liver nodules and scar tissue Irregular heartbeat Recurring inflammation of the sac that [diagnose-me.com]
• Tissue iron overload from sideroblastic anemia may act similar to hereditary hemochromatosis with liver cirrhosis, diabetes, congestive heart failure, and cardiac arrhythmias. [encyclopedia.lubopitko-bg.com]
Over a lifetime, problems related to iron overload, including congestive heart failure and cirrhosis, can become life-threatening issues. [encyclopedia.com]
Advanced HH can affect the patient’s organs, including the pancreas (diabetes), liver (hepatomegaly, abnormal liver function tests), pituitary gland (amenorrhea, decreased libido, erectile dysfunction), and heart (arrhythmias, congestive heart failure [mdedge.com]
Consequently, they can live long enough so that problems related to iron overload, including congestive heart failure and cirrhosis, become life-threatening issues. [sickle.bwh.harvard.edu]
Other symptoms of SA include: Pale skin color Rapid heart rate, or tachycardia Headaches Heart palpitations Weakness and fatigue Chest pain Types of SA There are two main types of sideroblastic anemia: inherited and acquired. [webmd.com]
PHYSICAL FINDINGS & CLINICAL PRESENTATION The symptoms for sideroblastic anemia are the same for any anemia: • Symptoms include fatigue, weakness, palpitations, shortness of breath, headaches, irritability, and chest pain. • Physical findings may include [encyclopedia.lubopitko-bg.com]
The symptoms and signs of congenital sideroblastic anemia (CSA) in children are primarily related to the anemia and its severity: Fatigue, weakness Irritability Exercise/feeding intolerance Exertional dyspnea Headache, vertigo Pale or yellow skin Some [danafarberbostonchildrens.org]
Periodic Fevers & Flare-ups Often, NOMID syndrome causes bouts of fevers (starting in infancy), accompanied by flare-ups of the rash, increased pain in the joints, headaches, red eyes and other symptoms. [autoinflammatory.org]
Clinical manifestations of megaloblastic anemia may include hyporexia, lethargy, headache, pallor, diarrhea, and paresthesia in the hands and feet. [bloodgenetics.com]
Suspicion of sideroblastic anemia is raised if a patient presents with microcytic anemia associated with high serum iron and ferritin, and transferrin overload.
A complete blood count in sideroblastic anemia often reveals anemia, varying from mild to severe . In sideroblastic anemia, the peripheral blood film reveals dimorphic red blood cells, with a predominantly microcytic picture. However, cases with macrocytic or normocytic pictures have also been noted . Most cases of dimorphism in sideroblastic anemia is a combination of microcytic and normocytic erythrocytes .
Bone marrow analysis by aspiration and biopsy is the gold standard investigation for sideroblastic anemia and it shows the ringed sideroblasts, observed with the Prussian blue stain, as developing red blood cells with accumulation of iron in the mitochondria forming a ring around the nucleus. Erythroid hyperplasia is also revealed in bone marrow analysis. Sideroblasts may also be seen in iron deficiency anemia after replenishing the iron stores. This may mask an underlying sideroblastic anemia . During bone marrow analysis, the megakaryocytes and myelocytes should also be analyzed in detail to exclude a potential myelodysplastic syndrome.
In cases of anemia-ataxia syndromes, a magnetic resonance imaging (MRI) of the posterior cranial fossa is required, so as to exclude intracranial causes, such as tumors and other space-occupying lesions around the cerebellum.
- Microcytic Anemia
The characteristic hypochromic, microcytic anemia typically becomes manifest in the first three decades of life. Hematologic response to pyridoxine is variable and rarely complete. [ncbi.nlm.nih.gov]
This abnormality of red cell production manifests as a hypochromic microcytic anemia with an elevated RDW, which results from a dimorphic population of cells. [thebigl.co]
A unique patient with sideroblastic anemia and thrombocytosis with a recurrent and ultimately fatal thromboembolic phenomenon is described. [ncbi.nlm.nih.gov]
19 In addition, RARS is characterized by over-expression of mitochondrial ferritin ( Figure 2D ), encoded by the FTMT gene. 3, 20 – 22 RARS-T is a myelodysplastic/myeloproliferative neoplasm characterized by anemia with ring sideroblasts and marked thrombocytosis [haematologica.org]
Refractory anemia with ring sideroblasts with thrombocytosis variant (RARS-T; JAK2 v617f mutation predominant), which has both sideroblastic anemia and thrombocytosis, is an additional consideration as a distinct entity.  Half of RARS-T patients carry [emedicine.medscape.com]
- Transferrin Increased
Decreased ferritin increases synthesis of transferrin (increasing TIBC); such as seen in iron deficiency anemia. [forums.studentdoctor.net]
- Ferritin Increased
Decreased ferritin increases synthesis of transferrin (increasing TIBC); such as seen in iron deficiency anemia. [forums.studentdoctor.net]
- Bone Marrow with Ringed Sideroblasts
Forty-six percent of erythroblasts in the bone marrow were ringed sideroblasts. Laboratory findings showed an IgG-kappa monoclonal gammopathy. [ncbi.nlm.nih.gov]
Complete blood count (CBC): microcytic anemia, Bone marrow biopsy : ringed sideroblasts seen on blood smears. These are RBC precursors appear with excess iron in their mitochondria (form a ring around the inside of the cell). [stepwards.com]
The ICD code D641 is used to code Sideroblastic anemia Sideroblastic anemia or sideroachrestic anemia is a form of anemia in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes). [icd.codes]
marrow aspirate: ring sideroblasts Ringed sideroblasts are seen in the bone marrow. [en.wikipedia.org]
• Bone marrow shows the classic ringed sideroblasts not seen in normal bone marrow tissue.The ringed sideroblasts represent iron storage in the mitochondria of normoblasts. TREATMENT The underlying cause determines the course of treatment. [encyclopedia.lubopitko-bg.com]
- Bone Marrow with Erythroid Hyperplasia
Bone marrow shows erythroid hyperplasia with a maturation arrest. In excess of 40% of the developing erythrocytes are ringed sideroblasts. Serum iron, percentage saturation and ferritin are increased. [en.wikipedia.org]
marrow erythroid : erythroid hyperplasia, may be mild to moderate dysplasia; markedly increased iron stores, ringed sideroblasts 15% of marrow erythroblasts, identify with iron stain on marrow smear, has nucleus completely or partially (at least one [pathologyoutlines.com]
Generally, the treatment of sideroblastic anemia depends on the causes, and treatment of acquired sideroblastic anemia comprises, most importantly, de-exposure to the triggers or precipitants.
Treatment of sideroblastic anemia includes the removal of the causative toxins, and administration of vitamin B1, B6, or B12. Reports have revealed that acquired and hereditary forms of sideroblastic anemia respond to vitamin B6 (pyridoxine), therefore, it is recommended in all cases of sideroblastic anemia. Vitamin B12 has also been noted to effectively treat sideroblastic anemia .
Bone marrow transplant is the last option of treatment and it is indicated for patients that are unresponsive to pyridoxine treatment . It is also reserved for cases requiring frequent blood transfusions .
Prognosis is variable, and mainly depends on the particular etiology of sideroblastic anemia. Generally, reversible causes do not have a bad prognosis, as the symptoms are usually mild to moderate . Congenital sideroblastic anemia and some acquired cases are associated with significant morbidity and mortality, as are cases which are associated with myelodysplastic syndromes, cases unabated by medical intervention, and cases requiring frequent blood transfusions.
Mortality from sideroblastic anemia is mainly from hemochromatosis following leukemia or blood transfusions. Leukemia carries a worse prognostic sign, while thrombocytosis constitutes a good prognostic sign . Morbidity in congenital sideroblastic anemia encompasses neuromuscular diseases sequel to mitochondrial protein defects. These neuromuscular diseases may compromise involuntary activities such as respiration, thus, increasing morbidity significantly, and mortality as well.
Sideroblastic anemia could be acquired or inherited.
Hereditary sideroblastic anemia most commonly results from a defective X-linked recessive gene known as ALAS2. This gene is responsible for the formation of an enzyme which plays a vital role in heme synthesis. This gene is located in band 11.21 of the X chromosome. This genetic abnormality usually becomes symptomatic before the age of 30, but may remain undiagnosed till after the fourth decade of life. Other congenital forms of sideroblastic anemia are autosomal or caused by mitochondrial abnormalities. However, up to 40% of hereditary sideroblastic anemia are X-linked .
Acquired sideroblastic anemia occurs secondary to alcohol toxicity, exposure to certain toxins, substance abuse, pyridoxine deficiency, drugs such as isoniazid, cycloserine, pyrazinamide, and chloramphenicol, or as a sequela of myelodysplastic syndromes. Acquired sideroblastic anemia may also constitute a complication of some immune disorders, metabolic disorders, or malignancies.
There are, however, some cases of sideroblastic anemia with unknown causes, which are described as idiopathic.
Congenital sideroblastic anemia usually presents before the age of 30, however, some cases remain undiagnosed till after the fourth decade of life  . Hereditary sideroblastic anemia is more common among men. Acquired sideroblastic anemia occurs more commonly in the senior population with a median age of occurrence at 74 years .
Generally, there is no ethnic predilection concerning the development of sideroblastic anemia.
Sideroblasts are abnormal normoblasts with an excessive mitochondrial accumulation of iron, forming a ringed shape around the nucleus. The basis for the formation of sideroblasts is impaired heme synthesis. Congenital causes of sideroblastic anemia include an X-linked mutation of genes involved in the synthesis of heme, iron-sulfur clusters and mitochondrial proteins . The X-linked gene defect involves the δ- aminolevulinate synthase (ALAS2), the first enzyme in the heme synthesis pathway. The mitochondrial abnormality commonly affects the erythroid mitochondrial transporter SLC25A38.
Such impaired heme production leads to reduced hemoglobin production with the development of abnormally shaped hypochromic microcytic red blood cells. These cells precede the ringed sideroblasts present in the bone marrow, which is pathognomonic of sideroblastic anemia. In some cases of sideroblastic anemia, however, red blood cells could be normocytic or macrocytic. There is usually a presence of dysmorphic red blood cells.
Acquired sideroblastic anemia may be prevented with dietary modifications including the avoidance of zinc-containing supplements and alcohol. Prenatal diagnosis of sideroblastic anemia and genetic counseling have remained crucial for the successful management of congenital sideroblastic anemia. This allows for the early beginning of management of the disease and prevention of complications.
Sideroblastic anemia is a group of hematologic disorders characterized by ineffective erythropoiesis in the presence of adequate iron, leading to the accumulation of iron in the red blood cells and subsequent sideroblasts in the bone marrow . It may be caused by genetic mutations in the genes responsible for the production of enzymes involved in the synthesis of heme or mitochondrial proteins. Other causes may be external factors such as toxic ingestion, interfering with the production of these proteins.
Therefore, the presence of iron for heme synthesis in the absence of the heme synthesis apparatus renders iron unused which, in turn, accumulates in the mitochondria around the nucleus. These sideroblasts are the diagnostic feature of sideroblastic anemia .
Sideroblastic anemia usually presents with features of anemia and iron overload. Iron overload is also evident by findings of high serum ferritin, iron and transferrin saturation. However, the diagnostic investigation for sideroblastic anemia is bone marrow biopsy and aspiration which reveals the diagnostic feature of sideroblasts.
Treatment of sideroblastic anemia depends on the cause. Acquired types are managed by discontinuation of the triggers. All cases of sideroblastic anemia require treatment with B-vitamins, although some cases will require blood transfusion and bone marrow transplant.
Sideroblastic anemia is a group of blood diseases in which the part of the hemoglobin, which carries oxygen in red blood cells, is not properly formed. This condition could either be inherited or caused by external factors such as lead toxicity, alcohol overuse, drugs, and vitamin deficiencies.
It usually results in anemia, a state of reduced oxygen-carrying capacity of the blood. Another key problem with this condition is that iron, which is used to form the abnormal hemoglobin, is present in excessive amounts in the red blood cells, forming what doctors call sideroblasts, immature red blood cells with excess iron in them.
Sideroblastic anemia may be caused by genetic abnormalities in the chemicals needed for the production of the part of the hemoglobin which carries iron. These forms are inherited and can start to manifest in childhood. Other causes are due to external factors mentioned above. In a few cases, however, doctors may not be able to tell the cause.
The inherited form of this diseases occurs more frequently in men than women, and usually causes symptoms before the patient turns 30. The acquired forms occur mostly in the elderly. This disease can, however affect persons of any race.
Anemia and too much iron in the blood are key features of this disease. Anemia presents with dizziness, excessive tiredness, lightheadedness, a rapid heartbeat, fast and difficult breathing, and paleness of the eye, mouth and palms. Overtime, if the condition remains untreated, it could lead to heart disease and liver damage.
Aspiration and biopsy of the bone marrow is the standard test to confirm a diagnosis of sideroblastic anemia. The bone marrow is that part deep inside certain bones of the body, especially the long bones, where blood cells are produced. This part of the bone is reached through a biopsy needle inserted through the skin and some contents of the marrow is drawn for analysis. This analysis will reveal the presence of the sideroblasts which are defined above.
The treatment of this condition depends on the cause. If it is acquired from external factors or triggers, such factors are eliminated. However, treatment with vitamin B6 and B12 is often successful for sideroblastic anemia. In patients who fail to respond to treatment with B vitamins, blood transfusion becomes necessary. Because iron overload can be a problem from blood transfusion, drugs that clear off excess iron would also be considered.
In severe cases and in younger patients, transplanting the bone marrow may successfully treat this condition.
Avoiding alcohol, hard drugs and food items containing zinc may help to prevent sideroblastic anemia. However, in those with the genetic defects, an early diagnosis, usually at pregnancy, is advisable in families with such history. Outcome is usually bad in cases that are inherited, and not so unfavorable in cases due to external factors.
- May A, Bishop DF. The molecular biology and pyridoxine responsiveness of X-linked sideroblastic anaemia. Haematologica. 1998 Jan;83(1):56-70.
- Cazzola M, Invernizzi R. Sideroblastic anemias. In: Young NS, Gerson SL, High KA, editors. Clinical Hematology. Philadelphia: Mosby Elsevier; 2005. pp. 721–32.
- Camaschella C. Recent advances in the understanding of inherited sideroblastic anaemia. Br J Haematol. 2008 Oct;143(1):27-38. doi:
10.1111/j.1365-2141.2008.07290.x. Epub 2008 Jul 14.
- Cortesão E, Vidan J, Pereira J, et al. Onset of X-linked sideroblastic anemia in the fourth decade. Haematologica. 2004 Oct. 89(10):1261-3.
- Furuyama K, Harigae H, Kinoshita C, et al. Late-onset X-linked sideroblastic anemia following hemodialysis. Blood. 2003 Jun 1. 101(11):4623-4.
- Hadnagy C. Primary acquired sideroblastic anemia and myelodysplastic syndrome from a geriatric point of view. Z Gerontol. 1991 Mar-Apr. 24(2):105-9.
- Matthes T. [Sideroblastic anemias]. Ther Umsch. 2006 Jan;63(1):25-33.
- Linker CA. Blood. McPhee SJ, Papadakis MA, Tierney LM, eds. Current Medical Diagnosis and Treatment. 45th ed. New York, NY: McGraw Hill; 2006. 486.
- Cheng DS, Kushner JP, Wintrobe MM. Idiopathic refractory sideroblastic anemia: incidence and risk factors for leukemic transformation. Cancer. 1979 Aug. 44(2):724-31.
- Cotter PD, May A, Fitzsimons EJ, et al. Late-onset X-linked sideroblastic anemia. Missense mutations in the erythroid delta-aminolevulinate synthase (ALAS2) gene in two pyridoxine-responsive patients initially diagnosed with acquired refractory anemia and ringed sideroblasts. J Clin Invest. 1995 Oct. 96(4):2090-6.
- Gattermann N, Retzlaff S, Wang YL, et al. Heteroplasmic point mutations of mitochondrial DNA affecting subunit I of cytochrome c oxidase in two patients with acquired idiopathic sideroblastic anemia. Blood. 1997 Dec 15. 90(12):4961-72.
- Tuckfield A, Ratnaike S, Hussein S, Metz J. A novel form of hereditary sideroblastic anaemia with macrocytosis. Br J Haematol. 1997 May. 97(2):279-85.
- Stavem P, Rørvik TO, Rootwelt K, Josefsen JO. Severe iron deficiency causing loss of ring sideroblasts. Scand J Haematol. 1983 Oct. 31(4):389-91.
- Sztern B, de Saint-Georges A, Telerman A, Lustman F. [Major sideroblastosis corrected by simple administration of folates] [French]. Presse Med. 1984 Jul 14-21. 13(29):1789.
- Zoller WG, Hehlmann R. Sideroachrestic anemia with iron loading: treatment with desferrioxamine. Klin Wochenschr. 1986 May 2. 64(9):417-22.
- Urban C, Binder B, Hauer C, Lanzer G. Congenital sideroblastic anemia successfully treated by allogeneic bone marrow transplantation. Bone Marrow Transplant. 1992 Oct. 10(4):373-5.
- González MI, Caballero D, Vázquez L, et al. Allogeneic peripheral stem cell transplantation in a case of hereditary sideroblastic anaemia. Br J Haematol. 2000 Jun. 109(3):658-60.