Sideroblastic anemia
Encyclopedia
Sideroblastic anemia or sideroachrestic anemia is a disease in which the bone marrow produces ringed sideroblasts rather than healthy red blood cell
s (erythrocytes). It may be caused either by a genetic disorder
or indirectly as part of myelodysplastic syndrome
, which can evolve into hematological malignancies
(especially acute myelogenous leukemia). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin
, which red blood cells need to transport oxygen efficiently.
Sideroblasts are atypical, abnormal nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in perinuclear mitochondria. Sideroblasts are seen in aspirates of bone marrow
.
GLRX5
has also been implicated.
of sideroblastic anemia is failure to completely form heme
molecules, whose biosynthesis takes place partly in the mitochondrion
. This leads to deposits of iron in the mitochondria that form a ring around the nucleus
of the developing red blood cell
. Sometimes the disorder represents a stage in evolution of a generalized bone marrow disorder that may ultimately terminate in acute leukemia.
The anemia is moderate to severe and dimorphic with marked anisocytosis
and poikilocytosis
. Basophilic stippling
is marked and target cells are common. Pappenheimer bodies
are present. The MCV
is decreased (i.e., a microcytic anemia
). The RDW
is increased with the red blood cell
histogram shifted to the left. Leukocytes and platelet
s are normal. 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. The TIBC
is normal to decreased. Stainable marrow hemosiderin is increased.
therapy. Some cases have been reported that the anemia is reversed or heme level is improved through use of moderate to high doses of pyrodoxine (Vitamin B6). In severe cases of SBA, bone marrow transplant is also an option with limited information about the success rate. Some cases are listed on MedLine and various other medical sites. In the case of isoniazid
-induced sideroblastic anemia, the addition of B6 is sufficient to correct the anemia. Desferrioxamine is used to treat iron overload from transfusions.
Bone Marrow Transplant (BMT) is the last possible treatment.
1- Hereditary-80% are responsive, though the hematology does not revert completely to normal.
2- Primary acquired-40% are responsive, but the response may be slight and is usually suboptimal.
3- Secondary-60% are responsive, the response also depending on the effectiveness of the treatment of associated conditions.
Severe refractory sideroblastic anemias requiring regular transfusions and/or leukemic transformation (5-10%) significantly reduce life expectancy.
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
s (erythrocytes). It may be caused either by a genetic disorder
Genetic disorder
A genetic disorder is an illness caused by abnormalities in genes or chromosomes, especially a condition that is present from before birth. Most genetic disorders are quite rare and affect one person in every several thousands or millions....
or indirectly as part of myelodysplastic syndrome
Myelodysplastic syndrome
The myelodysplastic syndromes are a diverse collection of hematological medical conditions that involve ineffective production of the myeloid class of blood cells....
, which can evolve into hematological malignancies
Hematological malignancy
Hematological malignancies are the types of cancer that affect blood, bone marrow, and lymph nodes. As the three are intimately connected through the immune system, a disease affecting one of the three will often affect the others as well: although lymphoma is technically a disease of the lymph...
(especially acute myelogenous leukemia). In sideroblastic anemia, the body has iron available but cannot incorporate it into hemoglobin
Hemoglobin
Hemoglobin is the iron-containing oxygen-transport metalloprotein in the red blood cells of all vertebrates, with the exception of the fish family Channichthyidae, as well as the tissues of some invertebrates...
, which red blood cells need to transport oxygen efficiently.
Sideroblasts are atypical, abnormal nucleated erythroblasts (precursors to mature red blood cells) with granules of iron accumulated in perinuclear mitochondria. Sideroblasts are seen in aspirates of bone marrow
Bone marrow
Bone marrow is the flexible tissue found in the interior of bones. In humans, bone marrow in large bones produces new blood cells. On average, bone marrow constitutes 4% of the total body mass of humans; in adults weighing 65 kg , bone marrow accounts for approximately 2.6 kg...
.
Classification
Sideroblastic anemia is typically divided into subtypes based on its cause.- Hereditary or congenital sideroblastic anemia may be X-linked or autosomal.
| OMIM | Name | Gene |
|---|---|---|
| X-linked sideroblastic anemia (XLSA) | ALAS2 ALAS2 Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ALAS2 gene. ALAS2 is an aminolevulinic acid synthase.... |
|
| sideroblastic anemia with spinocerebellar ataxia Spinocerebellar ataxia Spinocerebellar ataxia is a progressive, degenerative, genetic disease with multiple types, each of which could be considered a disease in its own right.-Classification:... (ASAT) |
ABCB7 ABCB7 ATP-binding cassette sub-family B member 7, mitochondrial is a protein that in humans is encoded by the ABCB7 gene.-Interactions:ABCB7 has been shown to interact with Ferrochelatase.- External Links :*... |
|
| pyridoxine-refractory autosomal recessive sideroblastic anemia | SLC25A38 SLC25A38 SLC25A38 is a human gene.... |
|
| pyridoxine-responsive sideroblastic anemia | (vitamin B6 deficiency; pyridoxal phosphate required for heme synthesis) |
GLRX5
GLRX5
Glutaredoxin 5 also known as GLRX5 is a protein which in humans is encoded by the GLRX5 gene.- Clinical significance :Mutations in the GLRX5 gene have been associated with sideroblastic anemia....
has also been implicated.
- Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause.
Symptoms
Symptoms of sideroblastic anemia include skin paleness, fatigue, dizziness and enlarged spleen and liver. Heart disease, liver damage and kidney failure can result from iron buildup in these organs.Causes
The primary pathophysiologyPathophysiology
Pathophysiology is the study of the changes of normal mechanical, physical, and biochemical functions, either caused by a disease, or resulting from an abnormal syndrome...
of sideroblastic anemia is failure to completely form heme
Heme
A heme or haem is a prosthetic group that consists of an iron atom contained in the center of a large heterocyclic organic ring called a porphyrin. Not all porphyrins contain iron, but a substantial fraction of porphyrin-containing metalloproteins have heme as their prosthetic group; these are...
molecules, whose biosynthesis takes place partly in the mitochondrion
Mitochondrion
In cell biology, a mitochondrion is a membrane-enclosed organelle found in most eukaryotic cells. These organelles range from 0.5 to 1.0 micrometers in diameter...
. This leads to deposits of iron in the mitochondria that form a ring around the nucleus
Cell nucleus
In cell biology, the nucleus is a membrane-enclosed organelle found in eukaryotic cells. It contains most of the cell's genetic material, organized as multiple long linear DNA molecules in complex with a large variety of proteins, such as histones, to form chromosomes. The genes within these...
of the developing red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
. Sometimes the disorder represents a stage in evolution of a generalized bone marrow disorder that may ultimately terminate in acute leukemia.
- Toxins: lead, copper or zincZincZinc , or spelter , is a metallic chemical element; it has the symbol Zn and atomic number 30. It is the first element in group 12 of the periodic table. Zinc is, in some respects, chemically similar to magnesium, because its ion is of similar size and its only common oxidation state is +2...
poisoning - Drug-induced: ethanolEthanolEthanol, also called ethyl alcohol, pure alcohol, grain alcohol, or drinking alcohol, is a volatile, flammable, colorless liquid. It is a psychoactive drug and one of the oldest recreational drugs. Best known as the type of alcohol found in alcoholic beverages, it is also used in thermometers, as a...
, isoniazidIsoniazidIsoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...
, chloramphenicolChloramphenicolChloramphenicol is a bacteriostatic antimicrobial that became available in 1949. It is considered a prototypical broad-spectrum antibiotic, alongside the tetracyclines, and as it is both cheap and easy to manufacture it is frequently found as a drug of choice in the third world.Chloramphenicol is...
, cycloserineCycloserineCycloserine is an antibiotic effective against Mycobacterium tuberculosis. For the treatment of tuberculosis, it is classified as a second line drug, i.e...
, Oral Contraceptives - Nutritional: pyridoxine (Vitamin B6) or copperCopperCopper is a chemical element with the symbol Cu and atomic number 29. It is a ductile metal with very high thermal and electrical conductivity. Pure copper is soft and malleable; an exposed surface has a reddish-orange tarnish...
deficiency - Diseases: Rheumatoid arthritis, or multiple myeloma
- Genetic: ALA synthase deficiency (X-linked, associated with ALAS2ALAS2Delta-aminolevulinate synthase 2 also known as ALAS2 is a protein that in humans is encoded by the ALAS2 gene. ALAS2 is an aminolevulinic acid synthase....
)
Diagnosis
Ringed sideroblasts are seen in the bone marrow.The anemia is moderate to severe and dimorphic with marked anisocytosis
Anisocytosis
Anisocytosis is a medical term meaning that a patient's red blood cells are of unequal size. This is found in anemia and other blood conditions...
and poikilocytosis
Poikilocytosis
Poikilocytosis refers to the presence of poikilocytes in the blood. Poikilocytes are abnormally shaped red blood cells as seen on a blood film in humans and many wild and domestic species of animals, though they are common in some clinically normal small ruminants, particularly goats.Normal red...
. Basophilic stippling
Basophilic stippling
Basophilic stippling aka Punctate basophilia refers to an observation found when observing a blood smear, where erythrocytes display small dots at the periphery...
is marked and target cells are common. Pappenheimer bodies
Pappenheimer bodies
Pappenheimer bodies are abnormal granules of iron found inside red blood cells on routine blood stain.They are a type of inclusion body formed by phagosomes that have engulfed excessive amounts of iron. They appear as dense, blue-purple granules within the red blood cell and there are usually only...
are present. The MCV
Mean corpuscular volume
The mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
is decreased (i.e., a microcytic anemia
Microcytic anemia
Microcytic anemia is a generic term for any type of anemia characterized by small red blood cells. The normal mean corpuscular volume is 76-100 fL, with smaller cells as macrocytic....
). The RDW
Red blood cell distribution width
The red blood cell distribution width is a measure of the variation of red blood cell width that is reported as part of a standard complete blood count. Usually red blood cells are a standard size of about 6–8 μm. Certain disorders, however, cause a significant variation in cell size. Higher...
is increased with the red blood cell
Red blood cell
Red blood cells are the most common type of blood cell and the vertebrate organism's principal means of delivering oxygen to the body tissues via the blood flow through the circulatory system...
histogram shifted to the left. Leukocytes and platelet
Platelet
Platelets, or thrombocytes , are small,irregularly shaped clear cell fragments , 2–3 µm in diameter, which are derived from fragmentation of precursor megakaryocytes. The average lifespan of a platelet is normally just 5 to 9 days...
s are normal. 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
Ferritin
Ferritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
are increased. The TIBC
Total iron-binding capacity
Total iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. It is performed by drawing blood and measuring the maximum amount of iron that it can carry, which indirectly measures transferrin since transferrin is the most dynamic carrier...
is normal to decreased. Stainable marrow hemosiderin is increased.
Laboratory findings
- Increased ferritinFerritinFerritin is a ubiquitous intracellular protein that stores iron and releases it in a controlled fashion. The amount of ferritin stored reflects the amount of iron stored. The protein is produced by almost all living organisms, including bacteria, algae and higher plants, and animals...
levels - Normal total iron-binding capacityTotal iron-binding capacityTotal iron-binding capacity is a medical laboratory test that measures the blood's capacity to bind iron with transferrin. It is performed by drawing blood and measuring the maximum amount of iron that it can carry, which indirectly measures transferrin since transferrin is the most dynamic carrier...
- HematocritHematocritThe hematocrit or packed cell volume or erythrocyte volume fraction is the percentage of the concentration of red blood cells in blood. It is normally about 45% for men and 40% for women...
of about 20-30% - Serum Iron: High
- High transferrin saturationTransferrin saturationTransferrin saturation, abbreviated as TSAT and measured as a percentage, is a medical laboratory value. It is the ratio of serum iron and total iron-binding capacity, multiplied by 100. Of the transferrin that is available to bind iron, this value tells a clinician how much serum iron is actually...
- The mean corpuscular volumeMean corpuscular volumeThe mean corpuscular volume, or "mean cell volume" , is a measure of the average red blood cell size that is reported as part of a standard complete blood count....
or MCV is usually normal or low. - With lead poisoningLead poisoningLead poisoning is a medical condition caused by increased levels of the heavy metal lead in the body. Lead interferes with a variety of body processes and is toxic to many organs and tissues including the heart, bones, intestines, kidneys, and reproductive and nervous systems...
, see coarse basophilic stippling of red blood cells on peripheral blood smear - Specific test: Prussian Blue stain of RBC in marrow. Shows ringed sideroblasts.
- can also cause microcytic hypochromic anemia.
Treatment
Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietinErythropoietin
Erythropoietin, or its alternatives erythropoetin or erthropoyetin or EPO, is a glycoprotein hormone that controls erythropoiesis, or red blood cell production...
therapy. Some cases have been reported that the anemia is reversed or heme level is improved through use of moderate to high doses of pyrodoxine (Vitamin B6). In severe cases of SBA, bone marrow transplant is also an option with limited information about the success rate. Some cases are listed on MedLine and various other medical sites. In the case of isoniazid
Isoniazid
Isoniazid , also known as isonicotinylhydrazine , is an organic compound that is the first-line antituberculosis medication in prevention and treatment. It was first discovered in 1912, and later in 1951 it was found to be effective against tuberculosis by inhibiting its mycolic acid...
-induced sideroblastic anemia, the addition of B6 is sufficient to correct the anemia. Desferrioxamine is used to treat iron overload from transfusions.
Bone Marrow Transplant (BMT) is the last possible treatment.
Course and prognosis
Sideroblastic anemias are often described as responsive or non responsive in terms of increased Hb level to pharmacological doses of vitamin B6.1- Hereditary-80% are responsive, though the hematology does not revert completely to normal.
2- Primary acquired-40% are responsive, but the response may be slight and is usually suboptimal.
3- Secondary-60% are responsive, the response also depending on the effectiveness of the treatment of associated conditions.
Severe refractory sideroblastic anemias requiring regular transfusions and/or leukemic transformation (5-10%) significantly reduce life expectancy.
See also
- AnemiaAnemiaAnemia is a decrease in number of red blood cells or less than the normal quantity of hemoglobin in the blood. However, it can include decreased oxygen-binding ability of each hemoglobin molecule due to deformity or lack in numerical development as in some other types of hemoglobin...
- SiderosisSiderosisSiderosis is the deposition of iron in tissue.When used without qualification, it usually refers to an environmental disease of the lung.Also Siderosis Bulbi, deposition of iron into the eye causing injury as the material chemically reacts with tissues and cells.-Causative agent:Iron oxide present...
- List of hematologic conditions
- Hematopoietic stem cell transplantation