Sideroblastic anemia
| Sideroblastic anemia | |
|---|---|
| Classification and external resources | |
 Sideroblast |
|
| ICD-10 | D64.0-D64.3 |
| ICD-9 | 285.0 |
| OMIM | 301310 206000 300751 |
| DiseasesDB | 12110 |
| MeSH | D000756 |
Sideroblastic anemia or sideroachrestic anemia is a disease in which the bone marrow produces ringed sideroblasts rather than healthy red blood cells (erythrocytes).[1] It may be caused either by a genetic disorder or indirectly as part of myelodysplastic syndrome,[2] 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.[3] Sideroblasts are seen in aspirates of bone marrow.
Contents |
[edit] Classification
Sideroblastic anemia is typically divided into subtypes based on its cause.
- Hereditary or congenital sideroblastic anemia may be X-linked[4] or autosomal.
| OMIM | Name | Gene |
|---|---|---|
| 300751 | X-linked sideroblastic anemia (XLSA) | ALAS2 |
| 301310 | sideroblastic anemia with spinocerebellar ataxia (ASAT) | ABCB7 |
| 205950 | pyridoxine-refractory autosomal recessive sideroblastic anemia | SLC25A38 |
| 206000 | pyridoxine-responsive sideroblastic anemia | (vitamin B6 deficiency; pyridoxal phosphate required for heme synthesis) |
GLRX5 has also been implicated.[5]
- Acquired, or secondary, sideroblastic anemia develops after birth and is divided according to its cause.
[edit] 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.[6]
[edit] Causes
The primary pathophysiology 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.
- Toxins: lead, copper or zinc poisoning
- Drug-induced: ethanol, isoniazid, chloramphenicol, cycloserine, Oral Contraceptives
- Nutritional: pyridoxine (Vitamin B6) or copper deficiency
- Diseases: Rheumatoid arthritis, or multiple myeloma
- Genetic: ALA synthase deficiency (X-linked, associated with ALAS2)[7]
[edit] Diagnosis
Ringed sideroblasts are seen in the bone marrow.
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 platelets 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.
[edit] Laboratory findings
- Increased ferritin levels
- Normal total iron-binding capacity
- Hematocrit of about 20-30%
- Serum Iron: High
- High transferrin saturation
- The mean corpuscular volume or MCV is usually normal or low.
- With lead poisoning, 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.
[edit] Treatment
Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietin therapy.[8] 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.
[edit] 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.
[edit] See also
[edit] References
- ^ Caudill JS, Imran H, Porcher JC, Steensma DP (October 2008). "Congenital sideroblastic anemia associated with germline polymorphisms reducing expression of FECH". Haematologica 93 (10): 1582–4. doi:10.3324/haematol.12597. PMID 18698088. http://www.haematologica.org/cgi/pmidlookup?view=long&pmid=18698088.
- ^ Sideroblastic Anemias: Anemias Caused by Deficient Erythropoiesis at Merck Manual of Diagnosis and Therapy Professional Edition
- ^ "Sideroblast" at Dorland's Medical Dictionary
- ^ X-linked sideroblastic anemia at NLM Genetics Home Reference
- ^ Camaschella C (September 2008). "Recent advances in the understanding of inherited sideroblastic anaemia". Br. J. Haematol. 143 (1): 27–38. doi:10.1111/j.1365-2141.2008.07290.x. PMID 18637800.
- ^ Genetics Home Reference: Genetic Conditions > X-linked sideroblastic anemia Reviewed October 2006. Retrieved on 5 Mars, 2009
- ^ Aivado M, Gattermann N, Rong A, et al. (2006). "X-linked sideroblastic anemia associated with a novel ALAS2 mutation and unfortunate skewed X-chromosome inactivation patterns". Blood Cells Mol. Dis. 37 (1): 40–5. doi:10.1016/j.bcmd.2006.04.003. PMID 16735131. http://linkinghub.elsevier.com/retrieve/pii/S1079-9796(06)00089-1.
- ^ Papadakis, Maxine A.; Tierney, Lawrence M.; McPhee, Stephen J. (2005). "Sideroblastic Anemia". Current Medical Diagnosis & Treatment, 2006. McGraw-Hill Medical. ISBN 0-07-145410-1.
[edit] External links
- GeneReviews/NCBI/NIH/UW entry on X-Linked Sideroblastic Anemia and Ataxia
- Sideroblastic Anemias: Introduction - Information Center for Sickle Cell and Thalassemic Disorders
- A concise description of this group of diseases from the Iron Disorders Institute
- Anemia, Sideroblastic at NIH's Office of Rare Diseases
- Sideroblastic Anemias Information Center
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