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词条 Diamond–Blackfan anemia
释义

  1. Signs and symptoms

  2. Genetics

     Molecular basis 

  3. Diagnosis

  4. Treatment

  5. History

     Notable cases 

  6. See also

  7. References

  8. External links

{{Infobox medical condition (new)
| name = Diamond–Blackfan anemia
| synonyms = Blackfan-Diamond anemia, inherited pure red cell aplasia,[1] inherited erythroblastopenia[2]
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| field = Hematology
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Diamond–Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy.[3] DBA causes low red blood cell counts (anemia), without substantially affecting the other blood components (the platelets and the white blood cells), which are usually normal. This is in contrast to Shwachman–Bodian–Diamond syndrome, in which the bone marrow defect results primarily in neutropenia, and Fanconi anemia, where all cell lines are affected resulting in pancytopenia.

A variety of other congenital abnormalities may also occur in DBA.

Signs and symptoms

Diamond–Blackfan anemia is characterized by normocytic or macrocytic anemia (low red blood cell counts) with decreased erythroid progenitor cells 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.[3] Low birth weight and generalized growth delay are sometimes observed. DBA patients have a modest risk of developing leukemia and other malignancies.{{Citation needed|date=September 2018}}

Genetics

Most pedigrees suggest an autosomal dominant mode of inheritance[1] with incomplete penetrance.[6] Approximately 10–25% of DBA occurs with a family history of disease.

About 25-50% of the causes of DBA have been tied to abnormal ribosomal protein genes.[1][4] The disease is characterized by genetic heterogeneity, affecting different ribosomal gene loci:[9] Exceptions to this paradigm have been demonstrated, such as with rare mutations of transcription factor GATA1[5][6] and advanced alternative splicing of a gene involved in iron metabolism, SLC49A1 (FLVCR1).[4][7]

DBA types
namechromosomegenotype[8]phenotype proteindisruption(cite)(cite)
DBA1[8] 19q13.2603474}}105650}} RPS19[16]{{rp>291}}(cite)
DBA2 8p23-p22 unknown606129}}
DBA3 10q22-q23602412}}610629}} RPS24[9][16]{{rp>291}}(cite)
DBA4 15q180472}}612527}} RPS17[10][16]{{rp>291}}
DBA5 3q29-qter180468}}612528}} RPL35A[21][16]{{rp>291}}(cite)
DBA6 1p22.1603634}}612561}} RPL5[23][16]{{rp>291}}
DBA7 1p36.1-p35604175}}612562}} RPL11[23][16]{{rp>291}}
DBA8 2p25603658}}612563}} RPS7[23][16]{{rp>291}}
DBA9 6p603632}}613308}} RPS10[8] 30S to 18S[30]
DBA10 12q603701}}613309}} RPS26 30S to 18S[31]
DBA11 17p13603704}}614900}} RPL26 30S to 18S[31]
DBA12 3p24604174}}615550}} RPL15 45S to 32S[33]
DBA13 14q603633}}615909}} RPS29
"other" TSR2,[34]RPS28,[34] GATA1

SLC49A1

(FLVCR1)[4]

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. 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 ribosome protein S19 (RPS19) gene on chromosome 19 at cytogenetic position 19q13.2. Some previously undiagnosed relatives of DBA patients were found to carry mutations, and also had increased adenosine deaminase levels in their red blood cells, but had 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.[11] The precise genetic defect in these families has not yet been delineated.

Malformations are seen more frequently with DBA6 RPL5 and DBA7 RPL11 mutations.[6]

The genetic abnormalities underpinning the combination of DBA with Treacher Collins syndrome (TCS)/mandibulofacial dysostosis (MFD) phenotypes are heterogeneous, including RPS26 (the known DBA10 gene), TSR2 which encodes a direct binding partner of RPS26, and RPS28.[34]

Molecular basis

The phenotype of DBA patients suggests a hematological stem cell defect specifically affecting the erythroid progenitor population. Loss of ribosomal function might be predicted to affect translation and protein biosynthesis broadly and impact many tissues. However, DBA is characterized by dominant inheritance, and arises from partial loss of ribosomal function, so it is possible that erythroid progenitors are more sensitive to this decreased function, while most other tissues are less affected.

Diagnosis

Typically, a diagnosis of DBA is made through a blood count and a bone marrow biopsy.

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.[12]

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.{{citation needed|date=September 2016}}About 20–25% of DBA patients may be identified with a genetic test for mutations in the RPS19 gene.

Treatment

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.[41] 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, adverse events from BMTs may exceed those from iron overloading.[42] A 2007 study[43] showed the efficacy of leucine and isoleucine supplementation in one patient. Larger studies are being conducted.{{citation needed|date=September 2016}}

History

First noted by Hugh W. Josephs in 1936,[1][45] the condition is however named for the pediatricians Louis K. Diamond and Kenneth Blackfan, who described congenital hypoplastic anemia in 1938.[13] Responsiveness to corticosteroids was reported in 1951.[1] In 1961, Diamond and colleagues presented longitudinal data on 30 patients and noted an association with skeletal abnormalities.[14] In 1997, a region on chromosome 19 was determined to carry a gene mutated in some DBA.[15][16] In 1999, mutations in the ribosomal protein S19 gene (RPS19) were found to be associated with disease in 42 of 172 DBA patients.[17] In 2001, a second DBA gene was localized to a region of chromosome 8, and further genetic heterogeneity was inferred.[52] Additional genes were subsequently identified.[8]

Notable cases

A girl named Audrey Nethery of Louisville, Kentucky has a large online following from her singing and dancing videos and has brought public attention to the very rare disease.[18] "The tiny dancer’s zest for the feel-happy, cool move packed, music pumping workout (Zumba) has inspired millions of people to fall in love with her. Subsequently, all the unexpected attention on Audrey has given her family a great opportunity to raise much needed awareness and funds for Diamond Blackfan Anemia (DBA)."[19] {{fact|date=October 2017}}

See also

  • List of hematologic conditions
  • Pure red cell aplasia

References

1. ^1 2 3 4 {{Cite book | last=Kaushansky | first=K |author2=Lichtman, M |author3=Beutler, E |author4=Kipps, T |author5=Prchal, J |author6= Seligsohn, U. |title=Williams Hematology | publisher=McGraw-Hill | year=2010 | chapter=35 |edition=8th |isbn= 978-0071621519}}
2. ^{{cite web|url=http://www.orpha.net/data/patho/Pro/en/BlackfanDiamond-FRenPro429.pdf|title=Diamond–Blackfan anemia|last=Tchernia|first=Gilbert|author2=Delauney, J|date=June 2000|publisher=Orpha.net|accessdate=1 January 2010}}
3. ^{{Cite web|url=https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia|title=Diamond-Blackfan anemia|last=Reference|first=Genetics Home|website=Genetics Home Reference|language=en|access-date=2018-04-17}}
4. ^1 2 {{Cite journal|last=Rey|first=Michelle A.|last2=Duffy|first2=Simon P.|last3=Brown|first3=Jennifer K.|last4=Kennedy|first4=James A.|last5=Dick|first5=John E.|last6=Dror|first6=Yigal|last7=Tailor|first7=Chetankumar S.|date=2008-11-01|title=Enhanced alternative splicing of the FLVCR1 gene in Diamond Blackfan anemia disrupts FLVCR1 expression and function that are critical for erythropoiesis|url=http://www.haematologica.org/content/93/11/1617|journal=Haematologica|language=en|volume=93|issue=11|pages=1617–1626|doi=10.3324/haematol.13359|issn=0390-6078|pmid=18815190}}
5. ^{{Cite journal|last=Sankaran|first=Vijay G.|last2=Ghazvinian|first2=Roxanne|last3=Do|first3=Ron|last4=Thiru|first4=Prathapan|last5=Vergilio|first5=Jo-Anne|last6=Beggs|first6=Alan H.|last7=Sieff|first7=Colin A.|last8=Orkin|first8=Stuart H.|last9=Nathan|first9=David G.|date=2012-07-02|title=Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia|url=http://www.jci.org/articles/view/63597|journal=Journal of Clinical Investigation|volume=122|issue=7|pages=2439–2443|doi=10.1172/jci63597|pmid=22706301|pmc=3386831}}
6. ^{{Cite journal|last=Parrella|first=Sara|last2=Aspesi|first2=Anna|last3=Quarello|first3=Paola|last4=Garelli|first4=Emanuela|last5=Pavesi|first5=Elisa|last6=Carando|first6=Adriana|last7=Nardi|first7=Margherita|last8=Ellis|first8=Steven R.|last9=Ramenghi|first9=Ugo|date=2014-07-01|title=Loss of GATA-1 full length as a cause of Diamond–Blackfan anemia phenotype|journal=Pediatric Blood & Cancer|volume=61|issue=7|pages=1319–1321|doi=10.1002/pbc.24944|pmid=24453067|issn=1545-5017|pmc=4684094}}
7. ^{{Cite journal|last=Crielaard|first=Bart J.|last2=Lammers|first2=Twan|last3=Rivella|first3=Stefano|date=2017-02-03|title=Targeting iron metabolism in drug discovery and delivery|url=http://www.nature.com/nrd/journal/vaop/ncurrent/abs/nrd.2016.248.html|journal=Nature Reviews Drug Discovery|language=en|volume=advance online publication|issue=6|pages=400|doi=10.1038/nrd.2016.248|pmid=28154410|pmc=5455971|issn=1474-1784}}
8. ^1 2 3 4 Online Mendelian Inheritance in Man. Diamond-Blackfan anemia. Johns Hopkins University. [https://omim.org/entry/105650]
9. ^{{cite journal |vauthors=Gazda HT, Grabowska A, Merida-Long LB |title=Ribosomal protein S24 gene is mutated in Diamond–Blackfan anemia |journal=Am. J. Hum. Genet. |volume=79 |issue=6 |pages=1110–8 |date=December 2006 |pmid=17186470 |pmc=1698708 |doi=10.1086/510020 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63474-0|display-authors=etal}}
10. ^{{cite journal |vauthors=Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D |title=Ribosomal protein S17 gene (RPS17) is mutated in Diamond–Blackfan anemia |journal=Hum. Mutat. |volume=28 |issue=12 |pages=1178–82 |date=December 2007 |pmid=17647292 |doi=10.1002/humu.20608}}
11. ^{{cite journal |vauthors=Gazda H, Lipton JM, Willig TN |title=Evidence for linkage of familial Diamond–Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease |journal=Blood |volume=97 |issue=7 |pages=2145–50 |date=April 2001 |pmid=11264183 |doi= 10.1182/blood.V97.7.2145|url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=11264183|display-authors=etal}}
12. ^{{Cite book | last=Williamson | first=MA | author2= Snyder, LM.|title=Wallach's Interpretation of Diagnostic Tests | publisher=Lippincott Williams & Wilkins | year=2015 | chapter=Chapter 9 |edition=10th|isbn= 9781451191769}}
13. ^{{cite journal | vauthors=Diamond LK, Blackfan KD | title=Hypoplastic anemia. | journal=Am. J. Dis. Child. | year=1938 | pages=464–467 | volume=56 }}
14. ^{{cite journal |vauthors=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 | pmid=13722603 | doi=10.1001/archpedi.1961.02080010405019 | issue=3}}
15. ^{{cite journal |vauthors=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 | pmid=9241274 | doi= 10.1038/ng0897-368}}
16. ^{{cite journal |vauthors=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 | pmid=9321770 | pmc= 1051068 | doi= 10.1136/jmg.34.9.779}}
17. ^{{cite journal |vauthors=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 | pmid=9988267 | doi= 10.1038/5951}}
18. ^{{Cite web | url=http://www.womenyoushouldknow.net/6-year-old-audrey-nethery-puts-her-rare-blood-disorder-in-spotlight-with-awesome-zumba-moves-sets-sights-ellen-show/ | title=6-Year-Old Audrey Nethery Puts Her Rare Blood Disorder in Spotlight with Awesome Zumba Moves, Sets Sights on Ellen Show| date=2015-04-27}}
19. ^{{Cite web | url=http://www.cosmopolitan.com/health-fitness/news/a45231/this-little-girl-is-better-at-zumba-than-youll-ever-be/ | title=This Little Girl with Diamond Blackfan Anemia is Better at Zumba Than You'll Ever be| date=2015-08-22}}
20. ^1 2 {{Cite journal | pmid = 20960466| year = 2010| author1 = Boria| first1 = I| title = The ribosomal basis of Diamond-Blackfan Anemia: Mutation and database update| journal = Human Mutation| volume = 31| issue = 12| pages = 1269–79| last2 = Garelli| first2 = E| last3 = Gazda| first3 = H. T.| last4 = Aspesi| first4 = A| last5 = Quarello| first5 = P| last6 = Pavesi| first6 = E| last7 = Ferrante| first7 = D| last8 = Meerpohl| first8 = J. J.| last9 = Kartal| first9 = M| last10 = Da Costa| first10 = L| last11 = Proust| first11 = A| last12 = Leblanc| first12 = T| last13 = Simansour| first13 = M| last14 = Dahl| first14 = N| last15 = Fröjmark| first15 = A. S.| last16 = Pospisilova| first16 = D| last17 = Cmejla| first17 = R| last18 = Beggs| first18 = A. H.| last19 = Sheen| first19 = M. R.| last20 = Landowski| first20 = M| last21 = Buros| first21 = C. M.| last22 = Clinton| first22 = C. M.| last23 = Dobson| first23 = L. J.| last24 = Vlachos| first24 = A| last25 = Atsidaftos| first25 = E| last26 = Lipton| first26 = J. M.| last27 = Ellis| first27 = S. R.| last28 = Ramenghi| first28 = U| last29 = Dianzani| first29 = I| doi = 10.1002/humu.21383| pmc=4485435}}
21. ^{{cite journal |vauthors=Cmejla R, Cmejlova J, Handrkova H, Petrak J, Pospisilova D |title=Ribosomal protein S17 gene (RPS17) is mutated in Diamond–Blackfan anemia |journal=Hum. Mutat. |volume=28 |issue=12 |pages=1178–82 |date=December 2007 |pmid=17647292 |doi=10.1002/humu.20608}}
22. ^1 {{cite journal |vauthors=Cmejla R, Cmejlova J, Handrkova H |title=Identification of mutations in the ribosomal protein L5 (RPL5) and ribosomal protein L11 (RPL11) genes in Czech patients with Diamond–Blackfan anemia |journal=Hum. Mutat. |volume= 30|issue= 3|pages= 321–7|date=February 2009 |pmid=19191325 |doi=10.1002/humu.20874|display-authors=etal}}
23. ^1 {{cite journal |vauthors=Farrar JE, Nater M, Caywood E |title=Abnormalities of the large ribosomal subunit protein, Rpl35a, in Diamond–Blackfan anemia |journal=Blood |volume=112 |issue=5 |pages=1582–92 |date=September 2008 |pmid=18535205 |pmc=2518874 |doi=10.1182/blood-2008-02-140012 |url=http://www.bloodjournal.org/cgi/pmidlookup?view=long&pmid=18535205|display-authors=etal}}
24. ^1 {{cite journal |vauthors=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 | pmid=11264183 | doi= 10.1182/blood.V97.7.2145}}
25. ^{{cite journal |vauthors=Gazda HT, Grabowska A, Merida-Long LB |title=Ribosomal protein S24 gene is mutated in Diamond–Blackfan anemia |journal=Am. J. Hum. Genet. |volume=79 |issue=6 |pages=1110–8 |date=December 2006 |pmid=17186470 |pmc=1698708 |doi=10.1086/510020 |url=http://linkinghub.elsevier.com/retrieve/pii/S0002-9297(07)63474-0|display-authors=etal}}
26. ^1 2 3 {{cite journal |author1=Gazda H. T. |author2=Sheen M. R. |author3=Vlachos A | year = 2008 | title = Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients | url = | journal = The American Journal of Human Genetics | volume = 83 | issue = 6| pages = 769–80 | doi = 10.1016/j.ajhg.2008.11.004 | pmid = 19061985 | pmc=2668101|display-authors=etal}}
27. ^1 2 3 {{cite journal | author = Gripp K. W. | author2 = Curry C | author3 = Olney A. H. | author4 = Sandoval C | author5 = Fisher J | author6 = Chong J. X. | author7 = UW Center for Mendelian Genomics | author8 = Pilchman L | author9 = Sahraoui R | author10 = Stabley D. L. | author11 = Sol-Church K | year = 2014 | title = Diamond-Blackfan anemia with mandibulofacial dystostosis is heterogeneous, including the novel DBA genes TSR2 and RPS28 | url = | journal = American Journal of Medical Genetics | volume = 164A | issue = 9| pages = 2240–9 | doi = 10.1002/ajmg.a.36633 | pmid = 24942156 | pmc=4149220}}
28. ^1 2 3 4 5 6 7 {{Cite book | last=Hoffbrand | first=AV |author2=Moss PAH|title=Essential Haematology | publisher=Wiley-Blackwell | year=2011 | chapter= |edition=6th |isbn= 978-1-4051-9890-5}}
29. ^1 {{cite journal | author=Hugh W. Josephs | title=Anaemia of infancy and early childhood| journal= Medicine (Baltimore) | year=1936| volume=15| issue=3| pages=307–451 | doi=10.1097/00005792-193615030-00001}}
30. ^Online Mendelian Inheritance in Man. Diamond-Blackfan anemia. Johns Hopkins University. [https://omim.org/entry/105650]
31. ^1 {{OMIM|603632}}
32. ^1 2 {{OMIM|603701}}
33. ^1 {{OMIM|604174}}
34. ^1 {{cite journal |vauthors=Pospisilova D, Cmejlova J, Hak J, Adam T, Cmejla R | title= Successful treatment of a Diamond–Blackfan anemia patient with amino acid leucine | journal= Haematologica | year=2007 | volume=92 | issue=5 | pmid=17562599 | doi= 10.3324/haematol.11498 | pages= e66–7}}
35. ^1 {{Cite journal | pmid = 8374573| year = 1993| author1 = Saunders| first1 = E. F.| title = Unexpected complications after bone marrow transplantation in transfusion-dependent children| journal = Bone Marrow Transplantation| volume = 12 Suppl 1| pages = 88–90| last2 = Olivieri| first2 = N| last3 = Freedman| first3 = M. H.}}
36. ^1 {{cite journal |vauthors=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 | pmid=11563775 | doi= 10.1097/00043426-200108000-00015}}
-->[20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][35][36]
}}

External links

{{Medical resources
| DiseasesDB =
| ICD10 = {{ICD10|D|61|0|d|60}}
| ICD9 = {{ICD9|284.01}}
| ICDO =
| OMIM = 105650
| MedlinePlus =
| eMedicineSubj = article/205695-overview
| eMedicineTopic =
| MeshID = D029503
}}
  • [https://www.ncbi.nlm.nih.gov/bookshelf/br.fcgi?book=gene&part=diamond-b GeneReviews/NCBI/NIH/UW entry on Diamond–Blackfan Anemia]
  • [https://www.ncbi.nlm.nih.gov/omim/105650,180468,180472,602412,603474,603632,603634,603658,603701,604175,606129,610629,612527,612528,612561,612562,612563,613308,613309,105650,180468,180472,602412,603474,603632,603634,603658,603701,604175,606129,610629,612527,612528,612561,612562,612563,613308,613309 OMIM entries on Diamond–Blackfan Anemia]
  • Diamond–Blackfan anemia Genetics Home Reference
{{Diseases of RBCs}}{{Disorders of translation and posttranslational modification}}{{DEFAULTSORT:Diamond-Blackfan anemia}}

3 : Ribosomopathy|Disorders of synthesis of DNA, RNA, and proteins|Aplastic anemias
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