Diamond-Blackfan anemia

Diamond-Blackfan anemia (DBA) is a congenitalerythroid aplasiathat usually presents in infancy. DBA patients have low red blood cellcounts (anemia). The rest of their blood cells (the plateletsand the white blood cells) are normal. A variety of other congenital abnormalities may also occur.

Clinical Features

Diamond-Blackfan anemia is characterized by anemia(low red blood cellcounts) with decreased erythroid progenitors in the bone marrow. This usually develops during the neonatalperiod. About 47% of affected individuals also have a variety of congenitalabnormalities, 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 leukemiaand other malignancies.

Diagnosis

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 deaminaselevels 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 testfor mutations in the RPS19 gene.

History

Diamond and Blackfandescribed congenital hypoplastic anemia in 1938. In 1961, Diamond and colleagues presented longitudinal data on 30 patients and noted an associated with skeletal abnormalities. In 1997a region on chromosome 19 was determined to carry a gene mutated in DBA. In 1999, mutations in the ribosomal protein S19 gene (RPS19) were found to be associated with disease in 42 of 172 DBA patients. 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.

Genetics

Approximately 10-25% of DBA cases have a family history of disease, and most pedigrees suggest an autosomal dominantmode of inheritance. The disease is characterized by genetic heterogeneity, with current evidence supporting the existence of at least three genesmutated in DBA. In 1997, a patient was identified who carried a rare balanced chromosomal translocationinvolving chromosome19 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. Linkageanalysis 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 ribosomeprotein S19 (RPS19) gene on chromosome 19 at cytogeneticposition 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 locusin the human genome.

Molecular Basis of Disease

The phenotype of DBA patients suggests a hematologicalstem celldefect 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 translationand protein biosynthesisand 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.

Clinical Management and Treatments

Corticosteroidscan 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. Some patients remained responsive to steroids, while efficacy waned in others. Blood transfusionscan also be used to treat severe anemia in DBA. Periods of remissionmay 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.

References

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 2005)
     |else= (2005)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Diamond Blackfan anemia: A paradigm for a ribosome-based disease.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Med. Hypotheses

}}{{qif

 |test={{{Volume|}}}
 |then= '

}}{{qif

 |test={{{Issue|}}}
 |then= ()

}}{{qif

 |test={{{Pages|}}}
 |then=: 

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 16239073

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 2005)
     |else= (2005)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Specific role for yeast homologs of the diamond blackfan anemia associated Rps19 protein in ribosome synthesis.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. J. Biol. Chem.

}}{{qif

 |test={{{Volume|}}}
 |then= '

}}{{qif

 |test={{{Issue|}}}
 |then= ()

}}{{qif

 |test={{{Pages|}}}
 |then=: 

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 16239073

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 2002)
     |else= (2002)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Marrow failure{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Hematology (Am. Soc. Hematol. Educ. Program)

}}{{qif

 |test={{{Volume|}}}
 |then= {{{Volume}}}

}}{{qif

 |test={{{Issue|}}}
 |then= ({{{Issue}}})

}}{{qif

 |test={{{Pages|}}}
 |then=: 58-72

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 12446419

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 2001)
     |else= (2001)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. J. Pediatr. Hematol. Oncol.

}}{{qif

 |test={{{Volume|}}}
 |then= 23

}}{{qif

 |test={{{Issue|}}}
 |then= (6)

}}{{qif

 |test={{{Pages|}}}
 |then=: 377-82

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 11563775

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 2001)
     |else= (2001)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Blood

}}{{qif

 |test={{{Volume|}}}
 |then= 97

}}{{qif

 |test={{{Issue|}}}
 |then= (7)

}}{{qif

 |test={{{Pages|}}}
 |then=: 2145-50

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 11264183

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 2001)
     |else= (2001)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Hematopoietic stem cell transplantation for Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Bone Marrow Transplant.

}}{{qif

 |test={{{Volume|}}}
 |then= 27

}}{{qif

 |test={{{Issue|}}}
 |then= (4)

}}{{qif

 |test={{{Pages|}}}
 |then=: 381-6

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 11313667

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 1999)
     |else= (1999)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Nat. Genet.

}}{{qif

 |test={{{Volume|}}}
 |then= 21

}}{{qif

 |test={{{Issue|}}}
 |then= (2)

}}{{qif

 |test={{{Pages|}}}
 |then=: 168-75

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 9988267

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 1997)
     |else= (1997)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Diamond-Blackfan anaemia: genetic homogeneity for a gene on chromosome 19q13 restricted to 1.8 Mb.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Nat. Genet.

}}{{qif

 |test={{{Volume|}}}
 |then= 16

}}{{qif

 |test={{{Issue|}}}
 |then= (4)

}}{{qif

 |test={{{Pages|}}}
 |then=: 368-71

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 9241274

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 1997)
     |else= (1997)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Diamond-Blackfan anaemia in a girl with a de novo balanced reciprocal X;19 translocation.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. J. Med. Genet.

}}{{qif

 |test={{{Volume|}}}
 |then= 34

}}{{qif

 |test={{{Issue|}}}
 |then= (9)

}}{{qif

 |test={{{Pages|}}}
 |then=: 779-82

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 9321770

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 1996)
     |else= (1996)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Diamond-Blackfan anemia. Natural history and sequelae of treatment.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Medicine (Baltimore)

}}{{qif

 |test={{{Volume|}}}
 |then= 75

}}{{qif

 |test={{{Issue|}}}
 |then= (2)

}}{{qif

 |test={{{Pages|}}}
 |then=: 77-8

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 8606629

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 1961)
     |else= (1961)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Congenital (erythroid) hypoplastic anemia: a 25 year study.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Am. J. Dis. Child.

}}{{qif

 |test={{{Volume|}}}
 |then= 102

}}{{qif

 |test={{{Issue|}}}
 |then= ({{{Issue}}})

}}{{qif

 |test={{{Pages|}}}
 |then=: 403-415

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}. PMID 13722603

• {{qif

  |test={{{Authorlink|}}}
  |then={{wikilink
        |1={{{Authorlink}}}
        |2={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}
        }}
  |else={{{Author|{{{Last|}}}{{{else{{{test|}}}|{{{test{{{test|}}}|{{{then|}}}}}}}}}}|then=, {{{First}}}}}}}}

}}{{qif

 |test={{{Coauthors|}}}
 |then=, {{{Coauthors}}}

}}{{qif

 |test={{{Date|}}}
 |then= ({{{Date}}})
 |else={{qif
   |test={{{Year|}}}
   |then={{qif
     |test={{{Month|}}}
     |then= ({{{Month}}} 1938)
     |else= (1938)
    }}
  }}

}}{{qif

 |test={{{Author|{{{Last|{{{Year|}}}}}}}}}
 |then=. 

}}{{qif

 |test={{{URL|}}}
 |then=[{{{URL}}}
 |else=

}} Hypoplastic anemia.{{qif

 |test={{{URL|}}}
 |then=]
 |else=

}}{{qif

 |test={{{Journal|}}}
 |then=. Am. J. Dis. Child.

}}{{qif

 |test={{{Volume|}}}
 |then= 56

}}{{qif

 |test={{{Issue|}}}
 |then= ({{{Issue}}})

}}{{qif

 |test={{{Pages|}}}
 |then=: 464-467

}}{{qif

 |test={{{ID|}}}
 |then=. {{{ID}}}

}}.

External links

• Diamond Blackfan Anæmia Support Group UK
• Diamond Blackfan Anemia Foundation (USA)
• Diamond Blackfan Anæmia Support Group
• Online Mendelian Inheritance in Man: Diamond-Blackfan anemia
• Diamond Blackfan Anemia Registry of North America (DBAR)

This article is licensed under the GNU Free Documentation License.
It uses material from the http://en.wikipedia.org/wiki/Diamond-Blackfan+anemia Wikipedia article Diamond-Blackfan anemia.