| Sideroblastic anemia |
| Classification and external resources |
A Ring Sideroblast visualized by Prussian blue stain |
| 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.
Ring sideroblasts are named so because of the arrangement of the iron granules in a ring form around the nucleus. However it does not take the ring to be complete in order to count a cell as a ring sideroblast. According to the 2008 WHO classification of the tumors of the hematopoietic and lymphoid tissues, it only needs 5 or more iron granules encircling one third or more of the nucleus.[4]
The WHO International Working Group on Morphology of MDS (IWGM-MDS) defined three types of sideroblasts:
- Type 1 sideroblasts: fewer than 5 siderotic granules in the cytoplasm
- Type 2 sideroblasts: 5 or more siderotic granules, but not in a perinuclear distribution
- Type 3 or ring sideroblasts: 5 or more granules in a perinuclear position, surrounding the nucleus or encompassing at least one third of the nuclear circumference.
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Contents
- 1 Classification
- 2 Symptoms
- 3 Causes
- 4 Diagnosis
- 5 Laboratory findings
- 6 Treatment
- 7 Course and prognosis
- 8 See also
- 9 References
- 10 External links
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Classification
Sideroblastic anemia is typically divided into subtypes based on its cause.
- Hereditary or congenital sideroblastic anemia may be X-linked[5] 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.[6]
- 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.[7]
Causes
By far the most common cause of sideroblastic anemia is excessive alcohol use. In this and other cases, 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, Linezolid,[8] oral contraceptives
- Nutritional: pyridoxine (Vitamin B6) or copper deficiency
- Diseases: Rheumatoid arthritis or multiple myeloma
- Genetic: ALA synthase deficiency (X-linked, associated with ALAS2)[9]
Diagnosis
Bone marrow aspirate: ring sideroblasts
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.
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.
Treatment
Occasionally, the anemia is so severe that support with transfusion is required. These patients usually do not respond to erythropoietin therapy.[10] 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.
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
- Anemia
- Siderosis
- List of hematologic conditions
- Hematopoietic stem cell transplantation
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.
- ^ Sideroblastic Anemias: Anemias Caused by Deficient Erythropoiesis at Merck Manual of Diagnosis and Therapy Professional Edition
- ^ "Sideroblast" at Dorland's Medical Dictionary
- ^ Diagnosis and classification of myelodysplastic syndrome: International Working Group on Morphology of myelodysplastic syndrome (IWGM-MDS) consensus proposals for the definition and enumeration of myeloblasts and ring sideroblasts Haematologica November 2008 93: 1712-1717; published ahead of print October 6, 2008, doi:10.3324/haematol.13405 http://www.haematologica.org/content/93/11/1712.full
- ^ 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
- ^ Saini, N; Jacobson, JO; Jha, S; Saini, V; Weinger, R (2012 Apr). "The perils of not digging deep enough--uncovering a rare cause of acquired anemia.". American journal of hematology 87 (4): 413–6. PMID 22120958.
- ^ 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.
- ^ 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.
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
- Rare Anemias Foundation
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Pathology: hematology, hematologic diseases of RBCs and megakaryocytes / MEP (D50-69,74, 280-287)
|
|
Red
blood cells |
| ↑ |
|
|
| ↓ |
| Anemia |
| Nutritional |
- Micro-: Iron deficiency anemia
- Macro-: Megaloblastic anemia
|
|
Hemolytic
(mostly Normo-) |
| Hereditary |
- enzymopathy: G6PD
- glycolysis
- hemoglobinopathy: Thalassemia
- Sickle-cell disease/trait
- HPFH
- membrane: Hereditary spherocytosis
- Minkowski-Chauffard syndrome
- Hereditary elliptocytosis
- Southeast Asian ovalocytosis
- Hereditary stomatocytosis
|
|
| Acquired |
- Drug-induced autoimmune
- Drug-induced nonautoimmune
- Hemolytic disease of the newborn
|
|
|
Aplastic
(mostly Normo-) |
- Hereditary: Fanconi anemia
- Diamond–Blackfan anemia
- Acquired: PRCA
- Sideroblastic anemia
- Myelophthisic
|
|
| Blood tests |
- MCV
- Normocytic
- Microcytic
- Macrocytic
- MCHC
|
|
|
| Other |
- Methemoglobinemia
- Sulfhemoglobinemia
- Reticulocytopenia
|
|
|
|
Coagulation/
coagulopathy |
| ↑ |
Hyper-
coagulability |
- primary: Antithrombin III deficiency
- Protein C deficiency/Activated protein C resistance/Protein S deficiency/Factor V Leiden
- Prothrombin G20210A
- acquired:Thrombocytosis
- DIC
- Congenital afibrinogenemia
- Purpura fulminans
- autoimmune
|
|
|
| ↓ |
Hypo-
coagulability |
| Thrombocytopenia |
- Thrombocytopenic purpura: ITP
- TM
- Heparin-induced thrombocytopenia
- May-Hegglin anomaly
|
|
| Platelet function |
- adhesion
- aggregation
- Glanzmann's thrombasthenia
- platelet storage pool deficiency
- Hermansky–Pudlak syndrome
- Gray platelet syndrome
|
|
| Clotting factor |
- Hemophilia
- von Willebrand disease
- Hypoprothrombinemia/II
- XIII
- Dysfibrinogenemia
|
|
|
|
|
|
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cell/phys (coag, heme, immu, gran), csfs
|
rbmg/mogr/tumr/hist, sysi/epon, btst
|
drug (B1/2/3+5+6), btst, trns
|
|
|
|
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Myeloid hematological malignancy/leukemia histology (ICD-O 9590–9989, C81–C96, 200–208)
|
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CFU-GM/
and other granulocytes |
|
CFU-GM
|
|
Myelocyte
|
AML: Acute myeloblastic leukemia (M0, M1, M2), APL/M3
MP (Chronic neutrophilic leukemia)
|
|
|
Monocyte
|
AML (AMoL/M5, Myeloid dendritic cell leukemia)
CML (Philadelphia chromosome, Accelerated phase chronic myelogenous leukemia)
|
|
|
Myelomonocyte
|
AML (M4)
MD-MP (Juvenile myelomonocytic leukemia, Chronic myelomonocytic leukemia)
|
|
|
Other
|
Histiocytosis
|
|
|
|
CFU-Baso
|
AML (Acute basophilic)
|
|
|
CFU-Eos
|
AML (Acute eosinophilic)
MP (Chronic eosinophilic leukemia/Hypereosinophilic syndrome)
|
|
|
| MEP |
|
CFU-Meg
|
AML (AMKL/M7)
MP (Essential thrombocytosis)
|
|
|
CFU-E
|
AML (Erythroleukemia/M6)
MP (Polycythemia vera)
MD (Refractory anemia, Refractory anemia with excess of blasts, Chromosome 5q deletion syndrome, Sideroblastic anemia, Paroxysmal nocturnal hemoglobinuria, Refractory cytopenia with multilineage dysplasia)
|
|
|
| CFU-Mast |
Mastocytoma (Mast cell leukemia, Mast cell sarcoma, Systemic mastocytosis)
Mastocytosis: Diffuse cutaneous mastocytosis · Erythrodermic mastocytosis · Generalized eruption of cutaneous mastocytosis (adult type) · Generalized eruption of cutaneous mastocytosis (childhood type) · Mast cell sarcoma · Solitary mastocytoma · Systemic mastocytosis · Xanthelasmoidal mastocytosis
|
|
| Multiple/unknown |
AML (Acute panmyelosis with myelofibrosis, Myeloid sarcoma) · MP (Myelofibrosis) · Acute biphenotypic leukaemia
|
|
|
|
cell/phys (coag, heme, immu, gran), csfs
|
rbmg/mogr/tumr/hist, sysi/epon, btst
|
drug (B1/2/3+5+6), btst, trns
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|
|
|
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Sex linkage: X-linked disorders
|
|
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X-linked recessive
|
|
| Immune |
- Chronic granulomatous disease (CYBB)
- Wiskott–Aldrich syndrome
- X-linked severe combined immunodeficiency
- X-linked agammaglobulinemia
- Hyper-IgM syndrome type 1
- IPEX
- X-linked lymphoproliferative disease
- Properdin deficiency
|
|
| Hematologic |
- Haemophilia A
- Haemophilia B
- X-linked sideroblastic anemia
|
|
| Endocrine |
- Androgen insensitivity syndrome/Kennedy disease
- KAL1 Kallmann syndrome
- X-linked adrenal hypoplasia congenita
|
|
| Metabolic |
- amino acid: Ornithine transcarbamylase deficiency
- Oculocerebrorenal syndrome
- dyslipidemia: Adrenoleukodystrophy
- carbohydrate metabolism: Glucose-6-phosphate dehydrogenase deficiency
- Pyruvate dehydrogenase deficiency
- Danon disease/glycogen storage disease Type IIb
- lipid storage disorder: Fabry's disease
- mucopolysaccharidosis: Hunter syndrome
- purine-pyrimidine metabolism: Lesch–Nyhan syndrome
- mineral: Menkes disease/Occipital horn syndrome
|
|
| Nervous system |
- X-linked mental retardation: Coffin–Lowry syndrome
- MASA syndrome
- X-linked alpha thalassemia mental retardation syndrome
- Siderius X-linked mental retardation syndrome
- eye disorders: Color blindness (red and green, but not blue)
- Ocular albinism (1)
- Norrie disease
- Choroideremia
- other: Charcot–Marie–Tooth disease (CMTX2-3)
- Pelizaeus–Merzbacher disease
- SMAX2
|
|
| Skin and related tissue |
- Dyskeratosis congenita
- Hypohidrotic ectodermal dysplasia (EDA)
- X-linked ichthyosis
- X-linked endothelial corneal dystrophy
|
|
| Neuromuscular |
- Becker's muscular dystrophy/Duchenne
- Centronuclear myopathy (MTM1)
- Conradi–Hünermann syndrome
- Emery–Dreifuss muscular dystrophy 1
|
|
| Urologic |
- Alport syndrome
- Dent's disease
- X-linked nephrogenic diabetes insipidus
|
|
| Bone/tooth |
- AMELX Amelogenesis imperfecta
|
|
| No primary system |
- Barth syndrome
- McLeod syndrome
- Smith–Fineman–Myers syndrome
- Simpson–Golabi–Behmel syndrome
- Mohr–Tranebjærg syndrome
- Nasodigitoacoustic syndrome
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|
|
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X-linked dominant
|
|
- X-linked hypophosphatemia
- Focal dermal hypoplasia
- Fragile X syndrome
- Aicardi syndrome
- Incontinentia pigmenti
- Rett syndrome
- CHILD syndrome
- Lujan–Fryns syndrome
- Orofaciodigital syndrome 1
- Craniofrontonasal dysplasia
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|
|
|
Genetic disorder, membrane: ABC-transporter disorders
|
|
| ABCA |
- ABCA1 (Tangier disease)
- ABCA3 (Surfactant metabolism dysfunction 3)
- ABCA4 (Stargardt disease 1, Retinitis pigmentosa 19)
- ABCA12 (Harlequin-type ichthyosis, Lamellar ichthyosis 2)
|
|
| ABCB |
- ABCB4 (Progressive familial intrahepatic cholestasis 3)
- ABCB7 (ASAT)
- ABCB11 (Progressive familial intrahepatic cholestasis 2)
|
|
| ABCC |
- ABCC2 (Dubin–Johnson syndrome)
- ABCC6 (Pseudoxanthoma elasticum)
- ABCC7 (Cystic fibrosis)
- ABCC8 (HHF1, TNDM2)
- ABCC9 (Dilated cardiomyopathy 1O)
|
|
| ABCD |
- ABCD1 (Adrenoleukodystrophy, Adrenomyeloneuropathy)
|
|
| ABCG |
- ABCG5 (Sitosterolemia)
- ABCG8 (Gallbladder disease 4, Sitosterolemia)
|
|
see also ABC transporters
- B structural
- perx
- skel
- cili
- mito
- nucl
- sclr
- DNA/RNA/protein synthesis
- membrane
- transduction
- trfk
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