|
|
| (166 intermediate revisions by 4 users not shown) |
| Line 1: |
Line 1: |
| | __NOTOC__ |
| {{Infobox_Disease | | | {{Infobox_Disease | |
| Name = {{PAGENAME}} | | | Name = {{PAGENAME}} | |
| Line 11: |
Line 12: |
| MeshID = D029503 | | | MeshID = D029503 | |
| }} | | }} |
| {{SI}} | | {{Diamond-Blackfan anemia}} |
|
| |
|
| {{CMG}}
| |
|
| |
|
| | {{CMG}} {{AE}} [[User:Roghayeh Marandi|Roghayeh Marandi]][mailto:parastoo@aol.in] |
|
| |
|
| | {{SK}} Erythrogenesis imperfecta; congenital pure red cell aplasia, hereditary pure red cell aplasia, familial pure red cell aplasia, RP: Ribosomal proteins, RPS: small ribosomal subunit, RPL: large ribosomal subunit, DBA: Diamond-Blackfan anemia, SDS: Shwachman-Diamond syndrome, AML: Acute myeloid leukemia, MDS: Myelodysplastic syndrome, BMF: Bone marrow failure, CHH: Cartilage-hair hypoplasia, CAMT: Congenital amegakaryocytic thrombocytopenia, HbF: Hemoglobin F |
|
| |
|
| ==Overview==
| |
| '''Diamond-Blackfan anemia''' (DBA) is a [[congenital]] [[erythroid]] [[aplasia]] that usually presents in [[infancy]]. DBA patients have low [[red blood cell]] counts ([[anemia]]). The rest of their blood cells (the [[platelet]]s and the [[white blood cell]]s) are normal. A variety of other congenital abnormalities may also occur.
| |
|
| |
|
| ==Clinical Features== | | ==[[Diamond-Blackfan anemia overview|Overview]]== |
|
| |
|
| Diamond-Blackfan anemia is characterized by [[anemia]] (low [[red blood cell]] counts) with decreased erythroid [[progenitors]] in the [[bone marrow]]. This usually develops during the [[neonatal]] period. About 47% of affected individuals also have a variety of [[congenital]] abnormalities, including [[craniofacial]] malformations, thumb or upper limb abnormalities, cardiac defects, [[urogenital]] malformations, and [[cleft palate]]. Low birth weight and generalized growth retardation are sometimes observed. DBA patients have a modest risk of developing [[leukemia]] and other malignancies. | | ==[[Diamond-Blackfan anemia historical perspective|Historical Perspective]]== |
|
| |
|
| ==Diagnosis== | | ==[[Diamond-Blackfan anemia pathophysiology|Pathophysiology]]== |
|
| |
|
| A diagnosis of DBA is made on the basis of anemia, low [[reticulocyte]] (immature red blood cells) counts, and diminished erythroid precursors in bone marrow. Features that support a diagnosis of DBA include the presence of congenital abnormalities, [[macrocytosis]], elevated [[fetal hemoglobin]], and elevated [[adenosine deaminase]] levels in red blood cells. Most patients are diagnosed in the first two years of life. However, some mildly affected individuals only receive attention after a more severely affected family member is identified. About 20-25% of DBA patients may be identified with a [[genetic test]] for mutations in the [[RPS19]] gene.
| | ==[[Diamond-Blackfan anemia causes|Causes]]== |
|
| |
|
| ==History== | | ==[[Diamond-Blackfan anemia differential diagnosis|Differentiating Diamond-Blackfan anemia from other Diseases]]== |
|
| |
|
| Diamond and [[Kenneth Blackfan|Blackfan]] described congenital [[hypoplastic]] anemia in 1938.<ref>{{cite journal | author=Diamond LK, Blackfan, KD | title=Hypoplastic anemia. | journal=Am. J. Dis. Child. | year=1938 | pages=464-467 | volume=56 }} </ref> In 1961, Diamond and colleagues presented [[longitudinal]] data on 30 patients and noted an association with skeletal abnormalities. <ref>{{cite journal | author=Diamond LK, Allen DW, Magill FB | title= Congenital (erythroid) hypoplastic anemia: a 25 year study. | journal=Am. J. Dis. Child. | year=1961 | pages=403-415 | volume=102 | id=PMID 13722603}}
| | ==[[Diamond-Blackfan anemia epidemiology and demographics|Epidemiology and Demographics]]== |
| </ref> In 1997 a region on chromosome 19 was determined to carry a gene mutated in DBA. <ref>{{cite journal | author= Gustavsson P, Willing TN, van Haeringen A, Tchernia G, Dianzani I, Donner M, Elinder G, Henter JI, Nilsson PG, Gordon L, Skeppner G, van't Veer-Korthof L, Kreuger A, Dahl N | title= Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb. | journal=Nat. Genet. | year=1997 | pages=368-71 | volume=16 | issue=4 | id=PMID 9241274}}</ref><ref>{{cite journal | author= Gustavsson P, Skeppner G, Johansson B, Berg T, Gordon L, Kreuger A, Dahl N | title= Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation. | journal=J. Med. Genet. | year=1997 | pages=779-82 | volume=34 | issue=9 | id=PMID 9321770}}</ref> In 1999, mutations in the ribosomal protein S19 gene (RPS19) were found to be associated with disease in 42 of 172 DBA patients.<ref>{{cite journal | author= Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, Ball S, Tchernia G, Klar J, Matsson H, Tentler D, Mohandas N, Carlsson B, Dahl N | title= The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. | journal=Nat. Genet. | year=1999 | pages=168-75 | volume=21 | issue=2 | id=PMID 9988267}}</ref> In 2001, it was determined that a second DBA gene lies in a region of chromosome 8 although evidence for further genetic heterogeneity was uncovered.<ref>{{cite journal | author=Gazda H, Lipton JM, Willig TN, Ball S, Niemeyer CM, Tchernia G, Mohandas N, Daly MJ, Ploszynska A, Orfali KA, Vlachos A, Glader BE, Rokicka-Milewska R, Ohara A, Baker D, Pospisilova D, Webber A, Viskochil DH, Nathan DG, Beggs AH, Sieff CA | title= Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease. | journal=Blood | year=2001 | pages=2145-50 | volume=97 | issue=7 | id=PMID 11264183}}</ref>
| |
|
| |
|
| ==Genetics== | | ==[[Diamond-Blackfan anemia risk factors|Risk Factors]]== |
|
| |
|
| Approximately 10-25% of DBA cases have a family history of disease, and most [[pedigrees]] suggest an [[autosomal dominant]] mode of inheritance. The disease is characterized by genetic [[heterogeneity]], with current evidence supporting the existence of at least three [[genes]] mutated in DBA. In 1997, a patient was identified who carried a rare balanced [[chromosomal translocation]] involving [[chromosome]] 19 and the X chromosome. This suggested that the affected gene might lie in one of the two regions that were disrupted by this [[cytogenetic]] [[anomaly]]. [[Genetic linkage|Linkage]] analysis in affected families also implicated this region in disease, and led to the cloning of the first DBA gene. About 20-25% of DBA cases are caused by mutations in the [[ribosomal|ribosome]] protein S19 (RPS19) gene on chromosome 19 at [[cytogenetic]] position 19q13.2. Interestingly, some previously undiagnosed relatives of DBA patients were found to carry mutations. These patients also had increased adenosine deaminase levels in their red blood cells but no other overt signs of disease. A subsequent study of families with no evidence of RPS19 mutations determined that 18 of 38 families showed evidence for involvement of an unknown gene on chromosome 8 at 8p23.3-8p22. The precise genetic defect in these families has not yet been delineated. In a further 7 families, both the chromosome 19 and chromosome 8 loci could be excluded for involvement, suggesting the existence of at least one other DBA [[locus (genetics)|locus]] in the [[human genome]].
| | ==[[Diamond-Blackfan anemia natural history, complications and prognosis|Natural History, Complications and Prognosis]]== |
|
| |
|
| ==Molecular Basis of Disease== | | ==Diagnosis== |
| | [[Diamond-Blackfan anemia history and symptoms|History and Symptoms]] | [[Diamond-Blackfan anemia physical examination|Physical Examination]] | [[Diamond-Blackfan anemia laboratory findings|Laboratory Findings]] | [[Diamond-Blackfan anemia electrocardiogram|Electrocardiogram]] | [[Diamond-Blackfan anemia chest x ray|Chest X Ray]] | [[Diamond-Blackfan anemia CT|CT]] | [[Diamond-Blackfan anemia MRI|MRI]] | [[Diamond-Blackfan anemia echocardiography or ultrasound|Echocardiography or Ultrasound]] | [[Diamond-Blackfan anemia other imaging findings|Other Imaging Findings]] | [[Diamond-Blackfan anemia other diagnostic studies|Other Diagnostic Studies]] |
|
| |
|
| The phenotype of DBA patients suggests a [[hematology|hematological]] [[stem cell]] defect specifically affecting the erythroid progenitor population. This is difficult to reconcile with the known function of the single known DBA gene. The RPS19 protein is involved in the production of [[ribosomes]]. As such, loss of RPS19 function would be predicted to affect [[translation (genetics)|translation]] and [[protein biosynthesis]] and have a much broader impact. Disease features may be related to the nature of RPS19 [[mutations]]. The disease is characterized by dominant inheritance, and therefore arises due to a partial loss of RPS19 protein function. It is possible that erythroid progenitors are acutely sensitized to this decreased function, while most other tissues are unaffected.
| | ==Treatment== |
| | [[Diamond-Blackfan anemia medical therapy|Medical Therapy]] | [[Diamond-Blackfan anemia surgery|Surgery]] | [[Diamond-Blackfan anemia cost-effectiveness of therapy|Cost-Effectiveness of Therapy]] | [[Diamond-Blackfan anemia future or investigational therapies|Future or Investigational Therapies]] |
|
| |
|
| ==Clinical Management and Treatments== | | ==Case Studies== |
| | [[Diamond-Blackfan anemia case study one|Case #1]] |
|
| |
|
| [[Corticosteroids]] can be used to treat anemia in DBA. In a large study of 225 patients, 82% initially responded to this therapy, although many side effects were noted.<ref>{{cite journal | author= Vlachos A, Klein GW, Lipton JM | title= The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia. | journal= J. Pediatr. Hematol. Oncol. | year=2001 | pages=377-82 | volume=23 | issue=6 | id=PMID 11563775}}</ref> Some patients remained responsive to steroids, while [[efficacy]] waned in others. [[Blood transfusions]] can also be used to treat severe anemia in DBA. Periods of [[remission]] may occur, during which transfusions and steroid treatments are not required. [[Bone marrow transplantation]] (BMT) can cure hematological aspects of DBA. This option may be considered when patients become transfusion-dependent because frequent transfusions can lead to iron overloading and organ damage. However, data from a large DBA patient registry indicated that [[adverse events]] in transfusion-dependent patients were more frequently caused by BMTs than iron overloading.
| | ==External Links== |
| | * [http://dbafoundation.org/ Diamond Blackfan Anemia Foundation (USA)] |
|
| |
|
| ==References==
| |
| {{Reflist|2}}
| |
|
| |
| ==External links==
| |
| * [http://www.diamondblackfan.org.uk/ Diamond Blackfan Anæmia Support Group UK]
| |
| * [http://dbafoundation.org/ Diamond Blackfan Anemia Foundation (USA)]
| |
| * [http://www.diamondblackfan.org/ Diamond Blackfan Anæmia Support Group]
| |
| * [http://www.dbar.org/ Diamond Blackfan Anemia Registry of North America (DBAR)]
| |
| * [http://news.bbc.co.uk/1/hi/health/4972182.stm "Designer baby bid gets go-ahead" at BBC News on 4 May 2006]
| |
| * [http://www.diamondblackfananemia.com/ Diamond Blackfan Anemia and You]
| |
| <br>
| |
| {{Hematology}} | | {{Hematology}} |
|
| |
|