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.

• Anemia

  There are two forms of sideroblastic anemia, i.e., inherited and acquired sideroblastic anemia. [ncbi.nlm.nih.gov]

• 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]

  Abstract The term "refractory anemia" in present day usage, has been applied to those cases of anemia that are not related to recognizable systemic disease and do not respond to currently known therapy. [annals.org]

• Fatigue

  A 3-month-old boy presented with decreased appetite, fatigue, and a nosebleed. [ashpublications.org]

  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: https://doi.org/10.1182/blood-2017-02-766881 A 3-month-old boy presented with decreased appetite, fatigue, and a nosebleed. [bloodjournal.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]

• Pallor

  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: • Poor growth/failure to thrive; • Hepatosplenomegaly (enlarged liver and spleen); and • Pallor (pale skin). [secure.ssa.gov]

  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]

• Swelling

  Joint signs are variably expressed and can lead to transient swelling without sequelae between crises, or to unpredictable anomalies of growth cartilage and long bones epiphyses suggestive of a pseudo-tumour, which, when biopsied, reveal hypertrophic [orpha.net]

  There was no history of jaundice, fever, bleeding episodes or swelling anywhere in his body. There was no history of any drug intake. The patient belonged to a Punjabi family and ancestors of both parents had migrated from Pakistan. [ijpmonline.org]

  Skin redness and swelling commonly occur after sunlight exposure, in contrast to the chronic, blistering lesions that characterize other cutaneous porphyrias. β-Carotene, and especially avoidance of sunlight, are important for prevention of cutaneous [ommbid.mhmedical.com]

  X-rays showed soft-tissue swelling and demineralization in her hands consistent with osteopenia and degenerative arthritis in both feet. [mdedge.com]

  Side effects vary and include pain and swelling at injection site. [encyclopedia.com]

• Constipation

  Symptoms include abdominal pain with constipation; metabolic acidosis, and may lead to shock, coma and death. Pb is a common cause of poisoning in children. Pb poisoning is treated with the chelating agent desferrioxamine. [med-ed.virginia.edu]

• Heart Disease

  Over time, severe medical problems such as heart disease and liver damage (cirrhosis) can result from the buildup of excess iron in these organs. Frequency This form of anemia is uncommon. [medlineplus.gov]

  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. [symptoma.com]

  This progressive deposition of toxic iron may result in an enlarged spleen or liver, liver disease, diabetes, impotence, arthritic signs, and heart disease, particularly cardiac arrhythmia. [encyclopedia.com]

  Heart disease, liver damage, and kidney failure can result from iron buildup in these organs. [7] Causes [ edit ] Causes of sideroblastic anemia can be categorized into three groups: congenital sideroblastic anemia, acquired clonal sideroblastic anemia [en.wikipedia.org]

  Adults who develop sideroblastic anemia may develop heart disease or cirrhosis. Providers can’t cure congenital SA, but they can manage symptoms and prevent serious medical complications with medications. [my.clevelandclinic.org]

• Hepatomegaly

  Hepatomegaly, liver dysfunction, anemia and lactic acidosis were chronic but non-pathognomonic presentations in this patient. [tp.amegroups.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]

  Hereditary sideroblastic anemia is associated with increased GI absorption of iron, causing signs of hemosiderosis (eventually, hepatomegaly, cardiomyopathy and, possibly, endocrine problems). [encyclopedia.lubopitko-bg.com]

  Abdomen ultrasonography showed diffuse increased echogenicity with mild hepatomegaly, and kidney ultrasonography revealed small cysts in both kidneys (Fig. 3). [journals.lww.com]

  […] the patients with Pearson syndrome manifested the condition before age 1 year, with 80% of them presenting with transfusion-dependent sideroblastic anemia. [20] During infancy and early childhood, failure to thrive, chronic diarrhea, and progressive hepatomegaly [emedicine.medscape.com]

• Jaundice

  As a result, jaundice and anemia were alleviated, but abnormal liver function and lactic acidosis remained refractory. [tp.amegroups.com]

  You may also note slight jaundice, caused by excessive iron accumulation in the liver, and petechiae or bruises, caused by thrombocytopenia. [encyclopedia.lubopitko-bg.com]

  Heart and liver failure may develop from excessive iron accumulation in these organs, causing dyspnea, exertional angina, and slight jaundice. However, other eipthelial manifestations and all neurologic manifestations are absent. [innvista.com]

  There was no history of jaundice, fever, bleeding episodes or swelling anywhere in his body. There was no history of any drug intake. The patient belonged to a Punjabi family and ancestors of both parents had migrated from Pakistan. [ijpmonline.org]

  He has a fever and you note jaundice. You order an ultrasound of his abdomen and find multiple gallstones. Lab results: Hct = .36 L/L; Hgb = 120 g/L. PBS at right. Your most likely diagnosis: A. Autoimmune hemolytic anemia B. Sickle cell anemia C. [med-ed.virginia.edu]

• Hepatosplenomegaly

  Physical findings: • Poor growth/failure to thrive; • Hepatosplenomegaly (enlarged liver and spleen); and • Pallor (pale skin). [secure.ssa.gov]

  Palpation may reveal enlarged lymph nodes, If iron accumulates in the liver and the patient has jaundice, palpation also may disclose hepatosplenomegaly. [encyclopedia.lubopitko-bg.com]

  Common features include fatigue, dizziness, a rapid heartbeat, pale skin, and an enlarged liver and spleen (hepatosplenomegaly). [medlineplus.gov]

  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. [symptoma.com]

• Conjunctival Pallor

  Physical examination may reveal conjunctival pallor, pale skin; some may have bronze-colored skin due to iron overload. [ncbi.nlm.nih.gov]

• Headache

  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]

  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]

  Central nervous system involvement is revealed by chronic headaches due to chronic meningitis with granulocytes. In the severe forms, intellectual deficit can occur. [orpha.net]

  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]

  Common symptoms of problems with the blood or blood forming tissue include fatigue, weakness, shortness of breath, fever, abnormal bleeding, headache, or bruising easily. Diseases of the blood may be diagnosed and treated by a hematologist. [rarediseases.info.nih.gov]

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 [10]. 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 [11]. Most cases of dimorphism in sideroblastic anemia is a combination of microcytic and normocytic erythrocytes [12].

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 [13]. 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.

• Erythroblast

  About one fourth of normal immature red cells, mostly proerythroblasts and basophilic erythroblasts, showed diffuse cytoplasmic positivity for HF, but very few were positive for MtF (0%-10%). [ncbi.nlm.nih.gov]

  Upper right, a late erythroblast with defective hemoglobinization; lower right, an early erythroblast with vacuolated cytoplasm and a late erythroblast with Pappenheimer bodies. MGG, x1,000. [haematologica.org]

  The iron-loaded erythroblasts, which are present in bone marrow, are called ring sideroblasts. These abnormal cells give the condition its name. [medlineplus.gov]

• 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]

  December 2017 for Microcytic Anemia – Red Blood Cell Pathology (RBC) Excellent course.Deals with the microcytic anemia starting from basics then pathology,clinical and investigations.Very useful and practical connections It was good .. but..! [lecturio.com]

• Thrombocytosis

  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. [15] 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]

  and linezolid. [14] Diagnosis [ edit ] Bone 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

  marrow general : hypercellular or normocellular marrow with erythroid hyperplasia Bone marrow erythroid : erythroid hyperplasia, may be mild to moderate dysplasia; markedly increased iron stores, ringed sideroblasts ≥ 15% of marrow erythroblasts, identify [pathologyoutlines.com]

  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]

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 [14].

If the disease is unresponsive to pyridoxine treatment, blood transfusion is opted for. Iron chelators such as deferoxamine should be used if iron overload complicates the transfusion [15].

Bone marrow transplant is the last option of treatment and it is indicated for patients that are unresponsive to pyridoxine treatment [16]. It is also reserved for cases requiring frequent blood transfusions [17].

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 [8]. 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 [9]. 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 [3].

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 [4] [5]. 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 [6].

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 [7]. 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 [1]. 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 [2].

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.

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