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Diamond-Blackfan anemia(DBA1)

MedGen UID:
266045
Concept ID:
C1260899
Congenital Abnormality
Synonyms: Aase syndrome; Aase-Smith syndrome II; Anemia congenital erythroid hypoplastic; Anemia Diamond Blackfan type; ANEMIA, CONGENITAL HYPOPLASTIC, OF BLACKFAN AND DIAMOND; Aregenerative anemia chronic congenital; Blackfan Diamond syndrome; Blackfan-Diamond disease; chronic congenital agenerative anemia; Congenital hypoplastic anemia; congenital pure red cell anemia; congenital pure red cell aplasia; DBA1; DIAMOND-BLACKFAN ANEMIA 1; Erythrogenesis imperfecta; inherited erythroblastopenia; Red cell aplasia, pure hereditary
Modes of inheritance:
Autosomal dominant inheritance
MedGen UID:
141047
Concept ID:
C0443147
Intellectual Product
Autosomal dominant inheritance refers to genetic conditions that occur when a mutation is present in one copy of a given gene (i.e., the person is heterozygous).
SNOMED CT: Chronic constitutional pure red cell aplasia (88854002); Diamond-Blackfan anemia (88854002); Chronic constitutional pure red cell anemia (88854002); Congenital pure red cell aplasia (234371002); Congenital red cell aplasia (88854002); Diamond-Blackfan syndrome (88854002)
 
Gene: RPS19
Cytogenetic location: 19q13.2
OMIM: 105650

Disease characteristics

Excerpted from the GeneReview: Diamond-Blackfan Anemia
Diamond-Blackfan anemia (DBA) in its classic form is characterized by a profound isolated normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in approximately 50% of affected individuals, and growth retardation in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life (median age of onset: 2 months). Eventually, 40% of affected individuals are corticosteroid dependent, 40% are transfusion dependent, and 20% go into remission. The phenotypic spectrum ranges from a mild form (e.g., mild anemia; no anemia with only subtle erythroid abnormalities; physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma. [from GeneReviews]
Full text of GeneReview (by section):
Summary  |  Diagnosis  |  Clinical Description  |  Differential Diagnosis  |  Management  |  Genetic Counseling  |  Resources  |  Molecular Genetics  |  References  |  Chapter Notes
Authors:
Catherine Clinton  |  Hanna T Gazda   view full author information

Additional descriptions

From OMIM
Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents in the first year of life. The main features are normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. Patients show growth retardation, and approximately 30 to 50% have craniofacial, upper limb, heart, and urinary system congenital malformations. The majority of patients have increased mean corpuscular volume, elevated erythrocyte adenosine deaminase activity, and persistence of hemoglobin F. However, some DBA patients do not exhibit these findings, and even in the same family, symptoms can vary between affected family members (summary by Landowski et al., 2013). Genetic Heterogeneity of Diamond-Blackfan Anemia A locus for DBA (DBA2; 606129) has been mapped to chromosome 8p23-p22. Other forms of DBA include DBA3 (610629), caused by mutation in the RPS24 gene (602412) on 10q22; DBA4 (612527), caused by mutation in the RPS17 gene (180472) on 15q; DBA5 (612528), caused by mutation in the RPL35A gene (180468) on 3q29; DBA6 (612561), caused by mutation in the RPL5 gene (603634) on 1p22.1; DBA7 (612562), caused by mutation in the RPL11 gene (604175) on 1p36; DBA8 (612563), caused by mutation in the RPS7 gene (603658) on 2p25; DBA9 (613308), caused by mutation in the RPS10 gene (603632) on 6p; DBA10 (613309), caused by mutation in the RPS26 (603701) gene on 12q; DBA11 (614900), caused by mutation in the RPL26 gene (603704) on 17p13; DBA12 (615550), caused by mutation in the RPL15 gene (604174) on 3p24; and DBA13 (615909), caused by mutation in the RPS29 gene (603633) on 14q. Boria et al. (2010) reviewed the molecular basis of Diamond-Blackfan anemia, emphasizing that it is a disorder of defective ribosome synthesis. Gazda et al. (2012) completed a large-scale screen of 79 ribosomal protein genes in families with Diamond-Blackfan anemia and stated that of the 10 known DBA-associated genes, RPS19 accounts for approximately 25% of patients; RPS24, 2%; RPS17, 1%; RPL35A, 3.5%; RPL5, 6.6%; RPL11, 4.8%; RPS7, 1%; RPS10, 6.4%; RPS26, 2.6%; and RPL26, 1%. Gazda et al. (2012) stated that in total these mutations account for approximately 54% of all DBA patients.  http://www.omim.org/entry/105650
From GHR
Diamond-Blackfan anemia is a disorder of the bone marrow. The major function of bone marrow is to produce new blood cells. In Diamond-Blackfan anemia, the bone marrow malfunctions and fails to make enough red blood cells, which carry oxygen to the body's tissues. The resulting shortage of red blood cells (anemia) usually becomes apparent during the first year of life. Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor). People with Diamond-Blackfan anemia have an increased risk of several serious complications related to their malfunctioning bone marrow. Specifically, they have a higher-than-average chance of developing myelodysplastic syndrome (MDS), which is a disorder in which immature blood cells fail to develop normally. Affected individuals also have an increased risk of developing certain cancers, including a cancer of blood-forming tissue known as acute myeloid leukemia (AML) and a type of bone cancer called osteosarcoma. Approximately half of individuals with Diamond-Blackfan anemia have physical abnormalities. They may have an unusually small head size (microcephaly) and a low frontal hairline, along with distinctive facial features such as wide-set eyes (hypertelorism); droopy eyelids (ptosis); a broad, flat bridge of the nose; small, low-set ears; and a small lower jaw (micrognathia). Affected individuals may also have an opening in the roof of the mouth (cleft palate) with or without a split in the upper lip (cleft lip). They may have a short, webbed neck; shoulder blades which are smaller and higher than usual; and abnormalities of their hands, most commonly malformed or absent thumbs. About one-third of affected individuals have slow growth leading to short stature. Other features of Diamond-Blackfan anemia may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), or eyes that do not look in the same direction (strabismus). Affected individuals may also have kidney abnormalities; structural defects of the heart; and, in males, the opening of the urethra on the underside of the penis (hypospadias). The severity of Diamond-Blackfan anemia may vary, even within the same family. Increasingly, individuals with "non-classical" Diamond-Blackfan anemia have been identified. This form of the disorder typically has less severe symptoms that may include mild anemia beginning in adulthood.  http://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia

Clinical features

Osteosarcoma
MedGen UID:
505326
Concept ID:
CN002426
Finding
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Cleft upper lip
MedGen UID:
504391
Concept ID:
CN000197
Finding
A gap in the `upper lip` (FMA:59817). This is a congenital defect resulting from nonfusion of tissues of the lip during embryonal development.
High palate
MedGen UID:
504397
Concept ID:
CN000211
Finding
Height of the palate more than 2 SD above the mean (objective) or palatal height at the level of the first permanent molar more than twice the height of the teeth (subjective).
Delayed cranial suture closure
MedGen UID:
504414
Concept ID:
CN000256
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Parietal foramina
MedGen UID:
505331
Concept ID:
CN002451
Finding
The presence of symmetrical and circular openings (foramina) in the parietal bone ranging in size from a few millimeters to several centimeters wide.
Strabismus
MedGen UID:
21337
Concept ID:
C0038379
Disease or Syndrome
Misalignment of the visual axes of the eyes. In comitant strabismus the degree of ocular misalignment does not vary with the direction of gaze. In noncomitant strabismus the degree of misalignment varies depending on direction of gaze or which eye is fixating on the target. (Miller, Walsh & Hoyt's Clinical Neuro-Ophthalmology, 4th ed, p641)
Hypertelorism
MedGen UID:
504419
Concept ID:
CN000296
Finding
Interpupillary distance more than 2 SD above the mean (alternatively, the appearance of an increased interpupillary distance or widely spaced eyes).
Delayed cranial suture closure
MedGen UID:
504414
Concept ID:
CN000256
Finding
Infants normally have two fontanels at birth, the diamond-shaped anterior fontanelle at the junction of the coronal and sagittal sutures, and the posterior fontanelle at the intersection of the occipital and parietal bones. The posterior fontanelle usually closes by the 8th week of life, and the anterior fontanel closes by the 18th month of life on average. This term applies if there is delay of closure of the fontanelles beyond the normal age.
Narrow chest
MedGen UID:
504594
Concept ID:
CN000728
Finding
Reduced width of the chest from side to side, associated with a reduced distance from the sternal notch to the tip of the shoulder.
Osteosarcoma
MedGen UID:
505326
Concept ID:
CN002426
Finding
A malignant bone tumor that usually develops during adolescence and usually affects the long bones including the tibia, femur, and humerus. The typical symptoms of osteosarcoma comprise bone pain, fracture, limitation of motion, and tenderness or swelling at the site of the tumor.
Parietal foramina
MedGen UID:
505331
Concept ID:
CN002451
Finding
The presence of symmetrical and circular openings (foramina) in the parietal bone ranging in size from a few millimeters to several centimeters wide.
Hypoplasia of the radius
MedGen UID:
428323
Concept ID:
CN002700
Finding
Underdevelopment of the radius.
Short thumb
MedGen UID:
429443
Concept ID:
CN008636
Finding
Hypoplasia (congenital reduction in size) of the `thumb` (FMA:24938).
Partial duplication of thumb phalanx
MedGen UID:
429885
Concept ID:
CN008782
Finding
A partial duplication, depending on severity leading to a broad or bifid appearance, affecting one or more of the phalanges of the thumb. As opposed to a complete duplication there is still a variable degree of fusion between the duplicated bones.
Pallor
MedGen UID:
504674
Concept ID:
CN000918
Finding
Abnormally `pale` (PATO:0000328) `skin` (FMA:7163).
Defect in the atrial septum
MedGen UID:
504879
Concept ID:
CN001485
Finding
Atrial septal defect (ASD) is a congenital abnormality of the `interatrial septum` (FMA:7108) that enables blood flow between the left and right atria via the interatrial septum.
Congestive heart failure
MedGen UID:
504881
Concept ID:
CN001488
Finding
The presence of an abnormality of cardiac function that is responsible for the failure of the heart to pump blood at a rate that is commensurate with the needs of the tissues or a state in which abnormally elevated filling pressures are required for the heart to do so. Heart failure is frequently related to a defect in myocardial contraction.
Neutropenia
MedGen UID:
18030
Concept ID:
C0027947
Disease or Syndrome
An abnormal decrease in the number of neutrophils, a type of white blood cell.
Thrombocytopenia
MedGen UID:
52737
Concept ID:
C0040034
Disease or Syndrome
A finding based on laboratory test results that indicate a decrease in number of platelets in a blood specimen.
Thrombocytosis
MedGen UID:
504993
Concept ID:
CN001712
Finding
Increased numbers of platelets in the peripheral blood.
Congenital hypoplastic anemia
MedGen UID:
505693
Concept ID:
CN004256
Finding
A type of `hypoplastic anemia` (HP:0001908) with congenital onset.
Neutropenia
MedGen UID:
18030
Concept ID:
C0027947
Disease or Syndrome
An abnormal decrease in the number of neutrophils, a type of white blood cell.

Professional guidelines

PubMed

Vlachos A, Dahl N, Dianzani I, Lipton JM
Eur J Hum Genet 2011 May;19(5) Epub 2011 Jan 19 doi: 10.1038/ejhg.2010.247. [Epub ahead of print] PMID: 21248735Free PMC Article

Recent clinical studies

Etiology

Watkins-Chow DE, Cooke J, Pidsley R, Edwards A, Slotkin R, Leeds KE, Mullen R, Baxter LL, Campbell TG, Salzer MC, Biondini L, Gibney G, Phan Dinh Tuy F, Chelly J, Morris HD, Riegler J, Lythgoe MF, Arkell RM, Loreni F, Flint J, Pavan WJ, Keays DA
PLoS Genet 2013;9(1):e1003094. Epub 2013 Jan 31 doi: 10.1371/journal.pgen.1003094. PMID: 23382688Free PMC Article
Neuwirtova R, Fuchs O, Holicka M, Vostry M, Kostecka A, Hajkova H, Jonasova A, Cermak J, Cmejla R, Pospisilova D, Belickova M, Siskova M, Hochova I, Vondrakova J, Sponerova D, Kadlckova E, Novakova L, Brezinova J, Michalova K
Ann Hematol 2013 Jan;92(1):11-8. Epub 2012 Sep 11 doi: 10.1007/s00277-012-1568-1. [Epub ahead of print] PMID: 22965552
Yazaki M, Kamei M, Ito Y, Konno Y, Wang R, Toki T, Ito E
J Pediatr Hematol Oncol 2012 May;34(4):293-5. doi: 10.1097/MPH.0b013e31824a20ab. PMID: 22510774
Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM
Blood 2012 Apr 19;119(16):3815-9. Epub 2012 Feb 23 doi: 10.1182/blood-2011-08-375972. [Epub ahead of print] PMID: 22362038Free PMC Article
Kuramitsu M, Sato-Otsubo A, Morio T, Takagi M, Toki T, Terui K, Wang R, Kanno H, Ohga S, Ohara A, Kojima S, Kitoh T, Goi K, Kudo K, Matsubayashi T, Mizue N, Ozeki M, Masumi A, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E, Hamaguchi I
Blood 2012 Mar 8;119(10):2376-84. Epub 2012 Jan 18 doi: 10.1182/blood-2011-07-368662. [Epub ahead of print] PMID: 22262766

Diagnosis

Gelbart D
JAAPA 2014 Apr;27(4):36-44. doi: 10.1097/01.JAA.0000442702.95598.fc. PMID: 24662257
Vlachos A, Dahl N, Dianzani I, Lipton JM
Eur J Hum Genet 2013 Oct;21(10) Epub 2013 Mar 6 doi: 10.1038/ejhg.2013.34. [Epub ahead of print] PMID: 23463023Free PMC Article
Pospisilova D, Cmejlova J, Ludikova B, Stary J, Cerna Z, Hak J, Timr P, Petrtylova K, Blatny J, Vokurka S, Cmejla R
Blood Cells Mol Dis 2012 Apr 15;48(4):209-18. Epub 2012 Mar 3 doi: 10.1016/j.bcmd.2012.02.002. [Epub ahead of print] PMID: 22381658
Kuramitsu M, Sato-Otsubo A, Morio T, Takagi M, Toki T, Terui K, Wang R, Kanno H, Ohga S, Ohara A, Kojima S, Kitoh T, Goi K, Kudo K, Matsubayashi T, Mizue N, Ozeki M, Masumi A, Momose H, Takizawa K, Mizukami T, Yamaguchi K, Ogawa S, Ito E, Hamaguchi I
Blood 2012 Mar 8;119(10):2376-84. Epub 2012 Jan 18 doi: 10.1182/blood-2011-07-368662. [Epub ahead of print] PMID: 22262766
Horos R, Ijspeert H, Pospisilova D, Sendtner R, Andrieu-Soler C, Taskesen E, Nieradka A, Cmejla R, Sendtner M, Touw IP, von Lindern M
Blood 2012 Jan 5;119(1):262-72. Epub 2011 Nov 4 doi: 10.1182/blood-2011-06-358200. [Epub ahead of print] PMID: 22058113

Therapy

Parrella S, Aspesi A, Quarello P, Garelli E, Pavesi E, Carando A, Nardi M, Ellis SR, Ramenghi U, Dianzani I
Pediatr Blood Cancer 2014 Jul;61(7):1319-21. Epub 2014 Jan 22 doi: 10.1002/pbc.24944. [Epub ahead of print] PMID: 24453067
Payne EM, Virgilio M, Narla A, Sun H, Levine M, Paw BH, Berliner N, Look AT, Ebert BL, Khanna-Gupta A
Blood 2012 Sep 13;120(11):2214-24. Epub 2012 Jun 25 doi: 10.1182/blood-2011-10-382986. [Epub ahead of print] PMID: 22734070Free PMC Article
Sjögren SE, Flygare J
ScientificWorldJournal 2012;2012:184362. Epub 2012 Apr 24 doi: 10.1100/2012/184362. PMID: 22619618Free PMC Article
Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM
Blood 2012 Apr 19;119(16):3815-9. Epub 2012 Feb 23 doi: 10.1182/blood-2011-08-375972. [Epub ahead of print] PMID: 22362038Free PMC Article
Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, Ohga S, Hara T, Hama A, Kojima S, Hasegawa D, Kosaka Y, Yanagisawa R, Koike K, Kanai R, Imai T, Hongo T, Park MJ, Sugita K, Ito E
Haematologica 2010 Aug;95(8):1293-9. Epub 2010 Apr 7 doi: 10.3324/haematol.2009.020826. [Epub ahead of print] PMID: 20378560Free PMC Article

Prognosis

Quarello P, Garelli E, Brusco A, Carando A, Mancini C, Pappi P, Vinti L, Svahn J, Dianzani I, Ramenghi U
Haematologica 2012 Dec;97(12):1813-7. Epub 2012 Jun 11 doi: 10.3324/haematol.2012.062281. [Epub ahead of print] PMID: 22689679Free PMC Article
Pospisilova D, Cmejlova J, Ludikova B, Stary J, Cerna Z, Hak J, Timr P, Petrtylova K, Blatny J, Vokurka S, Cmejla R
Blood Cells Mol Dis 2012 Apr 15;48(4):209-18. Epub 2012 Mar 3 doi: 10.1016/j.bcmd.2012.02.002. [Epub ahead of print] PMID: 22381658
Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM
Blood 2012 Apr 19;119(16):3815-9. Epub 2012 Feb 23 doi: 10.1182/blood-2011-08-375972. [Epub ahead of print] PMID: 22362038Free PMC Article
Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T
Transfus Clin Biol 2010 Sep;17(3):112-9. Epub 2010 Jul 23 doi: 10.1016/j.tracli.2010.06.001. [Epub ahead of print] PMID: 20655265Free PMC Article
Devlin EE, Dacosta L, Mohandas N, Elliott G, Bodine DM
Blood 2010 Oct 14;116(15):2826-35. Epub 2010 Jul 6 doi: 10.1182/blood-2010-03-275776. [Epub ahead of print] PMID: 20606162Free PMC Article

Clinical prediction guides

Aspesi A, Pavesi E, Robotti E, Crescitelli R, Boria I, Avondo F, Moniz H, Da Costa L, Mohandas N, Roncaglia P, Ramenghi U, Ronchi A, Gustincich S, Merlin S, Marengo E, Ellis SR, Follenzi A, Santoro C, Dianzani I
Gene 2014 Jul 25;545(2):282-9. Epub 2014 May 15 doi: 10.1016/j.gene.2014.04.077. [Epub ahead of print] PMID: 24835311Free PMC Article
Watkins-Chow DE, Cooke J, Pidsley R, Edwards A, Slotkin R, Leeds KE, Mullen R, Baxter LL, Campbell TG, Salzer MC, Biondini L, Gibney G, Phan Dinh Tuy F, Chelly J, Morris HD, Riegler J, Lythgoe MF, Arkell RM, Loreni F, Flint J, Pavan WJ, Keays DA
PLoS Genet 2013;9(1):e1003094. Epub 2013 Jan 31 doi: 10.1371/journal.pgen.1003094. PMID: 23382688Free PMC Article
Payne EM, Virgilio M, Narla A, Sun H, Levine M, Paw BH, Berliner N, Look AT, Ebert BL, Khanna-Gupta A
Blood 2012 Sep 13;120(11):2214-24. Epub 2012 Jun 25 doi: 10.1182/blood-2011-10-382986. [Epub ahead of print] PMID: 22734070Free PMC Article
Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM
Blood 2012 Apr 19;119(16):3815-9. Epub 2012 Feb 23 doi: 10.1182/blood-2011-08-375972. [Epub ahead of print] PMID: 22362038Free PMC Article
Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, Ohga S, Hara T, Hama A, Kojima S, Hasegawa D, Kosaka Y, Yanagisawa R, Koike K, Kanai R, Imai T, Hongo T, Park MJ, Sugita K, Ito E
Haematologica 2010 Aug;95(8):1293-9. Epub 2010 Apr 7 doi: 10.3324/haematol.2009.020826. [Epub ahead of print] PMID: 20378560Free PMC Article

Recent systematic reviews

Pennell DJ, Udelson JE, Arai AE, Bozkurt B, Cohen AR, Galanello R, Hoffman TM, Kiernan MS, Lerakis S, Piga A, Porter JB, Walker JM, Wood J; American Heart Association Committee on Heart Failure and Transplantation of the Council on Clinical Cardiology and Council on Cardiovascular Radiology and Imaging
Circulation 2013 Jul 16;128(3):281-308. Epub 2013 Jun 17 doi: 10.1161/CIR.0b013e31829b2be6. [Epub ahead of print] PMID: 23775258
Tsangaris E, Klaassen R, Fernandez CV, Yanofsky R, Shereck E, Champagne J, Silva M, Lipton JH, Brossard J, Michon B, Abish S, Steele M, Ali K, Dower N, Athale U, Jardine L, Hand JP, Odame I, Canning P, Allen C, Carcao M, Beyene J, Roifman CM, Dror Y
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Lieberman L, Dror Y
Curr Opin Pediatr 2006 Feb;18(1):15-21. doi: 10.1097/01.mop.0000192520.48411.fa. PMID: 16470156

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