Última actualización:
July 26, 2019
Años publicados: 1987, 1990, 1991, 1994, 1996, 1997, 1998, 1999, 2006, 2007, 2019
NORD gratefully acknowledges Muntaha Mahgoub, NORD Editorial Intern from the Massachusetts College of Pharmacy and Health Sciences, and Adrianna Vlachos, MD, Head, Bone Marrow Failure Program; Director, Diamond Blackfan Anemia Registry, Cohen Children’s Medical Center of New York; Hematology/Oncology and Stem Cell Transplantation, The Feinstein Institute for Medical Research of Northwell Health, for assistance in the preparation of this report.
Diamond Blackfan anemia (DBA) is a rare blood disorder that affects the bone marrow. The function of the bone marrow is to make new blood cells, including red blood cells (which carry oxygen to the body’s tissues), white blood cells (which help the body fight infections), and platelets (which help the body stop bleeding). In DBA the bone marrow cannot make enough red blood cells to meet the body’s needs. DBA is characterized by a shortage of red blood cells which usually becomes evident during the first year of life when the patient develops anemia. About half of the affected patients have abnormal physical abnormalities associated with DBA. The symptoms and physical findings associated with DBA vary greatly from person to person.
Diamond Blackfan anemia is characterized by moderate to severe deficiency of red blood cells (anemia). Sometimes white blood cells and platelets may be lower as well. Symptoms of anemia include rapid heartbeat, pale skin, sleepiness, irritability, poor appetite, and weakness. Approximately ninety percent of affected patients are diagnosed within the first year of life. The diagnosis is generally made by 3-4 months of age.
Approximately one-half of those affected have physical abnormalities, such as small head size; wide-set eyes; flat nose; small, low-set ears; small bottom jaw; recessed or small chin; cleft palate (an opening in the roof of the mouth with or without a cleft lip – a split in the upper lip); and small, missing or extra thumb(s). The neck may be short due to fused vertebrae and shoulder blades may be prominent. About one-third of affected individuals have slow growth leading to short stature.
Other features of DBA may include eye problems such as clouding of the lens of the eyes (cataracts), increased pressure in the eyes (glaucoma), kidney abnormalities; defects of the heart; and males may have hypospadias (a condition in which the urinary tract does not end at the tip of the penis). Many of these defects may need surgical correction.
A possible complication of DBA is the development of cancer at younger than expected ages. Patients with DBA have developed bone cancer (osteosarcoma), colon cancer, and leukemia (blood cancer called acute myeloid leukemia), among others. The patients are also at risk for a pre-leukemic syndrome called myelodysplastic syndrome which is another disorder caused by the bone marrow not making enough healthy blood cells.
Diamond Blackfan anemia is caused by changes (mutations) in ribosomal protein genes in about 80-85% of those affected. In the remaining 10-15% of patients, no abnormal genes have yet been identified.
A mutation in the RPS19 gene is the cause of DBA in about 25% of patients. Mutations have also been found in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26, and rarely in RPL15, RPL17, RPL19, RPL26, RPL27, RPL31, RPS15A, RPS20, RPS27, RPS28, RPS29, and TSR2. In a few patients, the disease is caused by a mutation in the GATA1 gene.
DBA caused by the ribosomal protein gene mutation follows autosomal dominant inheritance. Dominant genetic disorders occur when only a single copy of a non-working gene is necessary to cause a particular disease. The non-working gene can be inherited from either parent or can be the result of a mutated (changed) gene in the affected individual only. In approximately 45% of patients, the mutation is inherited from one affected parent. The remaining patients have no history of the disorder in their family, and develop the disorder because of a new (sporadic) gene mutation. The risk of passing the non-working gene from an affected parent to an offspring is 50% for each pregnancy. The risk is the same for males and females. The rare TSR2 and GATA1 gene mutations are inherited in affected males only from a mother who is an unaffected carrier.
Diamond Blackfan anemia affects approximately 5 to 7 people per million live births per year. Thus in the United States, with 4 million livebirths per year, there are approximately 25-35 new patients born per year. There are several approximately 5000 cases world-wide. There are an equal number of males and females with the disease.
The average age of presenting with anemia is two months and the average age of diagnosis with DBA is 3-4 months. Some tests that aid in diagnosing DBA are:
Treatment
When the patient presents with anemia, the usual initial treatment includes a red cell transfusion. If available, transfusions are usually the mainstay of treatment for the first year of life for the anemia of DBA. After the first year patients are started on a course of treatment with corticosteroids. This treatment can initially improve the red blood cell count in approximately 80% of people with DBA.
Red blood transfusions are used for those patients who do not respond to corticosteroid treatment. If the patient remains on chronic transfusion therapy (usually required every 3-4 weeks) then the patient will also require iron chelation. Iron chelation is necessary to unload the extra iron that accumulates when a person receives transfusions. If the iron is not removed then the person can develop iron overload in the heart, liver and endocrine organs and develop heart arrhythmias (abnormal heart rhythms), congestive heart failure, liver abnormalities and cirrhosis, diabetes, hypothyroidism, gonadal dysfunction, and other issues.
Some people have such mild signs and symptoms that they do not require treatment.
The only curative treatment for the anemia of DBA is bone marrow/stem cell transplantation. This treatment replaces damaged bone marrow with healthy stem cells from a donor. This can be done using an unaffected sibling or an unrelated donor.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact: https://www.clinicaltrialsregister.eu/
Diamond Blackfan Anemia Registry
The Feinstein Institute for Medical Research
350 Community Drive
Manhasset, NY 11040
Phone: (516) 562-3757
Toll-free: (888) 884-DBAR (3227)
Website: www.dbar.org
REVIEW ARTICLES
Bartels M, Bierings M. How I manage children with Diamond-Blackfan anaemia. Br J Haematol. 2019;184(2):123-133.
Vlachos A, Osorio DS, Atsidaftos E, et al. Increased prevalence of congenital heart disease in children with Diamond Blackfan anemia Suggests Unrecognized Diamond Blackfan anemia as a cause of congenital heart disease in the general population: A report of the Diamond Blackfan anemia registry. Circ Genom Precis Med. 2018;11(5):e002044.
Da Costa L, Narla A, Mohandas N. An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia. F1000Res. 2018;7.
Peffault de Latour R. Transplantation for bone marrow failure: current issues. Hematology Am Soc Hematol Educ Program. 2016;2016(1):90-98.
Lee JW, Yoon SS, Shen ZX, et al. Hematologic responses in patients with aplastic anemia treated with deferasirox: a post hoc analysis from the EPIC study. Haematologica. 2013;98(7):1045-8.
Dokal I, Vulliamy T. Inherited bone marrow failure syndromes. Haematologica. 2010;95(8):1236-40.
Vlachos A, Muir E. How I treat Diamond-Blackfan anemia. Blood 2010; 116(19):3715-3723. PMCID: PMC2981532
Ganapathi KA, Shimamura A. Ribosomal dysfunction and inherited marrow failure. Br J Haematol. 2008 May;141(3):376-87.
Naithani R, Chandra J, Narayan S, Singh V, Dutta AK. Diamond-Blackfan anemia: clinical features and treatment results in 4 cases. Hematology. 2006 Jun;11(3):193-5.
INTERNET
Diamond-Blackfan anemia | Genetic and Rare Diseases Information Center (GARD) https://rarediseases.info.nih.gov/diseases/6274/blackfan-diamond-syndrome Last updated: 12/1/2017. Accessed February 18, 2019.
Leblanc T. Blackfan-Diamond anemia. orpha.net. https://www.orpha.net/consor/cgi-bin/OC_Exp.php?lng=en&Expert=124 Last update: February 2009. Accessed February 17, 2019.
Diamond-Blackfan anemia. Genetics Home Reference. https://ghr.nlm.nih.gov/condition/diamond-blackfan-anemia#diagnosis Reviewed: September 2018. Accessed February 17, 2019.
Diamond Blackfan Anemia Foundation, Inc. Dbafoundation.org. https://dbafoundation.org Accessed February 17, 2019.
Diamond Blackfan Anemia | St. Louis Childrens Hospital. Stlouischildrens.org. https://www.stlouischildrens.org/conditions-treatments/diamond-blackfan-anemia
Accessed February 17, 2019.
Diamond-Blackfan Anemia in Children – Dana-Farber/Boston Children’s Cancer and Blood Disorders Center. Danafarberbostonchildrens.org. https://www.danafarberbostonchildrens.org/conditions/blood-disorders/diamond-blackfan-anemia.aspx?_ga=2.174180001.246350990.1550610817-1926909684.1550610815
Accessed February 16, 2019.
Diamond Blackfan Anaemia. Leukaemia Foundation. https://www.leukaemia.org.au/disease-information/diamond-blackfan-anaemia/
Posted February 5th, 2018. Accessed February 15, 2019.
NORD y la Fundación MedicAlert se han asociado en un nuevo programa para brindar protección a pacientes con enfermedades raras en situaciones de emergencia.
Aprende más https://rarediseases.org/patient-assistance-programs/medicalert-assistance-program/Asegurarse de que los pacientes y los cuidadores estén equipados con las herramientas que necesitan para vivir su mejor vida mientras manejan su condición rara es una parte vital de la misión de NORD.
Aprende más https://rarediseases.org/patient-assistance-programs/rare-disease-educational-support/Este programa de asistencia, primero en su tipo, está diseñado para los cuidadores de un niño o adulto diagnosticado con un trastorno raro.
Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View report