Diamond-Blackfan anemia is a rare form of anemia that is often accompanied by several physical anomalies. Blood workup may reveal a lack of production of red blood cells, however, other cell lines remain normal.
Diamond-Blackfan anemia (DBA) is a rare inherited bone marrow failure syndrome that usually presents in the first few years of life . Less than a quarter of cases are familial, following an autosomal dominant pattern . The majority of cases are sporadic mutations that can then be passed down to offspring.
DBA is thought to arise from a disturbance in ribosome formation, coded for by the ribosomal protein S19 (RPS19) gene . It is mainly defined by a hypoplastic, macrocytic anemia that may be accompanied by various congenital abnormalities . The white cell and platelet counts typically remain within, or just below, normal ranges .
DBA often presents with severe anemia in infancy or childhood, which may be fatal . Newborns may have a low birth weight, followed by growth retardation. Outward signs of disease are pallor, especially while feeding, and shortness of breath. There is usually no associated organomegaly.
It is estimated that half of the children affected by DBA also exhibit physical abnormalities. The craniofacial features of DBA are the most commonly occurring abnormalities, some of which are hypertelorism, microcephaly, microtia, cleft palate, and a flattened nasal bridge. Pierre-Robin syndrome, congenital glaucoma, and cataracts have also been described.
Musculoskeletal features include short stature, webbed neck, and upper limb deformities such as triphalangeal thumbs, and complete absence of the radius or forearm. Puberty may be delayed, however, the rest of the developmental history is normal. In contrast, intellectual disability is not a part of the syndrome. Other systems that are characteristically disturbed are the urogenital and cardiovascular systems . This results in conditions such as hypospadias, horseshoe kidneys, ventricular septal defect, atrial septal defect, and coarctation of the aorta.
In addition to the above, children with DBA have a higher risk of developing leukemia and various solid tumors, exemplified by acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and osteosarcoma .
Entire Body System
Patients with physical findings suggestive of Treacher Collins syndrome (TCS) or mandibulofacial dysostosis (MFD) and macrocytic anemia diagnostic of Diamond-Blackfan anemia (DBA) have been reported. [ncbi.nlm.nih.gov]
Lines, Mandibulofacial Dysostosis with Microcephaly: Mutation and Database Update, Human Mutation, 37, 2, (148-154), (2015). [doi.org]
Malformations are seen more frequently with DBA6 RPL5 and DBA7 RPL11 mutations.  The genetic abnormalities underpinning the combination of DBA with Treacher Collins syndrome (TCS)/ mandibulofacial dysostosis (MFD) phenotypes are heterogeneous, including [en.wikipedia.org]
Jaw & Teeth
The diagnosis of Diamond-Blackfan anemia can be made based on family history, prenatal genetic testing in cases of known mutations, as well as a raised erythrocyte adenosine deaminase (EAD) .
Further laboratory tests include:
- Complete blood count: A raised mean cell volume (MCV) may be present, with a normal white cell and platelet count, and a low percentage of reticulocyte count.
- Peripheral blood smear: This may show normochromic, macrocytic red blood cells.
- Bone marrow aspirate: This test is used to confirm the absence of red cell production in the bone marrow (erythroblastopenia). Furthermore, samples are tested for parvovirus B19, which can cause bone marrow suppression.
- Radiological: The skeletal deformities can be easily observed through various radiological means.
- Cardiac and renal function monitoring are also indicated.
About 40% of all DBA patients receive glucocorticoid treatment, but the disease specific mechanisms behind glucocorticoid treatment in DBA are not fully elucidated. [portal.research.lu.se]
Current treatment options, including steroid treatments and chronic transfusions, can lead to significant morbidity. [medicalxpress.com]
Therefore, in this study we analyzed our results in the management of this rare disease by different medical treatments. Design. [pediatrics.aappublications.org]
DBA was diagnosed at the age of 4 months, and the boy underwent treatment with transfusion and with prednisolone. [ncbi.nlm.nih.gov]
He is Coordinator of the International Working Group for Prognosis in MDS (IWG-PM) which generated the revised MDS classification system (the IPSS-R) and is now evaluating the impact of molecular mutations on this risk-based prognostic system. [med.stanford.edu]
Prognosis Prognosis varies among the different types of pure red cell aplasia (PRCA). Transient erythroblastopenia and other PRCA disorders in children and adults are benign with an excellent prognosis. [emedicine.medscape.com]
Prognosis The prognosis is generally good. However, complications of treatment and a higher incidence of cancer may reduce life expectancy. Disease severity depends on the quality and response to treatment. [orpha.net]
The prognosis depends upon response to treatment with patients responsive to non-toxic doses of corticosteroids having a better prognosis than transfusion-dependent patients. [tandfonline.com]
The etiology for the immunodeficiency remains unsolved and could be caused by an unknown gene effect or consequent to the DBA phenotype. [ncbi.nlm.nih.gov]
With regards to OS, we are now creating a conditional Rps19 CRISPR murine model, in order to clarify the contribution of both rp and p53 in the etiology of OS. [cancerres.aacrjournals.org]
Author information 1 Division of Cancer Epidemiology and Genetics, National Cancer Institute, National Institutes of Health, Bethesda, MD; 2 Stem Cell Program and Division of Hematology/Oncology, Children's Hospital Boston and Dana-Farber Cancer Institute [ncbi.nlm.nih.gov]
The Diamond Blackfan Anemia Registry of North America (DBAR) is designed to overcome these disadvantages to study the epidemiology and biology of DBA. [doi.org]
Seth Brodie 3, Settara C Chandrasekharappa 4, Frank X Donovan 4, Weiyin Zhou 3, Belynda D Hicks 1, 3, Joseph F Boland 1, 3, Meredith Yeager 1, 3, Kristine Jones 3, Bin Zhu 3, Mingyi Wang 3, Blanche P Alter 1, Sharon A Savage 1 1 Division of Cancer Epidemiology [jmg.bmj.com]
A major problem in understanding the pathophysiological mechanisms in DBA remains the lack of a suitable animal model. [ncbi.nlm.nih.gov]
Overall, to increase our understanding of genotype-phenotype correlation in DBA, and underlying pathophysiological mechanisms more generally, it crucial to further extend our genetic, and functional analysis of DBA-candidate genes, as well as compare, [learningcenter.ehaweb.org]
Gov't MeSH terms Anemia, Aplastic Anemia, Diamond-Blackfan/genetics Anemia, Diamond-Blackfan/pathology Anemia, Diamond-Blackfan/prevention & control* Animals Bone Marrow Diseases Disease Models, Animal* Genetic Therapy* Genetic Vectors/administration [ncbi.nlm.nih.gov]
Centers for Disease Control and Prevention. Recommendations to prevent and control iron deficiency in the United States. MMWR Recomm Rep. 1998;47(RR-3):1–29. 19. U.S. Preventive Services Task Force. [aafp.org]
Indeed, we showed that the diverse mutations affecting RPS19, the most frequently mutated ribosomal protein in DBA, prevent incorporation of the RPS19 into ribosomes, which affects ribosome biogenesis in patients. [anr.fr]
This work is or has been supported by grants from the National Heart Lung and Blood Institute (R01HL079571, R109MOHLKE), the Centers for Disease Control and Prevention, the Pediatric Cancer Foundation, the Diamond Blackfan Anemia Foundation and the Daniella [tandfonline.com]
- Lipton JM, Ellis SR. Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis. Hematol Oncol Clin North Am. 2009;23(2):261-282.
- Johns Hopkins University. Diamond-Blackfan Anemia 1, DBA1. Online Mendelian Inheritance in Man (OMIM). https://www.omim.org/entry/105650. Updated March 28, 2017. Accessed September 9, 2017.
- Vlachos A, Rosenberg PS, Atsidaftos E, Alter BP, Lipton JM. Incidence of neoplasia in Diamond Blackfan anemia: a report from the Diamond Blackfan Anemia Registry. Blood. 2012;119(16):3815-3819.
- Campagnoli MF, Ramenghi U, Armiraglio M, et al. RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat. 2008;29(7):911-920.
- Gazda HT, Sieff CA. Recent insights into the pathogenesis of Diamond-Blackfan anaemia. Br J Haematol. 2006;135(2):149-157.
- Ellis SR. Nucleolar stress in Diamond Blackfan anemia pathophysiology. Biochim Biophys Acta. 2014;1842(6):765-768.
- Alter BP, Giri N, Savage SA, et al. Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study. Br J Haematol. 2010;150(2):179-188.
- Clinton C, Gazda HT. Diamond-Blackfan Anemia. GeneReviews. https://www.ncbi.nlm.nih.gov/books/NBK7047/. Published 25 Jun, 2009. Updated 7 April, 2016. Accessed 18 September, 2017.