Diamond-Blackfan anemia
Diamond-Blackfan anemia | |
ICD-10 | D61.0 |
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ICD-9 | 284.01 |
OMIM | 105650 |
DiseasesDB | 29062 |
MeSH | D029503 |
Diamond-Blackfan anemia Microchapters |
Diagnosis |
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Treatment |
Case Studies |
Diamond-Blackfan anemia On the Web |
American Roentgen Ray Society Images of Diamond-Blackfan anemia |
Risk calculators and risk factors for Diamond-Blackfan anemia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Synonyms and keywords: Erythrogenesis imperfecta; congenital pure red cell aplasia, hereditary pure red cell aplasia, familial pure red cell aplasia
Overview
Historical Perspective
Pathophysiology
Causes
- A mutation in the RPS19 gene is the cause of DBA in about 25% of patients.
- Mutations in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS24, and RPS26, and rarely in RPL15, RPL17, RPL19, RPL26, RPL27, RPL31, RPS15A, RPS20, RPS27, RPS28, RPS29 have also been found.[1]
- Mutation in non-RP genes, TSR2, GATA1, and EPO.[1]
- 20 percent of patients still have no known genetic cause.[1]
Differentiating Diamond-Blackfan anemia from other Diseases
- Aplastic anemia
- Fanconi anemia
- Transient Erythroblastopenia of Childhood
- Shwachman-Diamond syndrome (SDS)[2]
- Pearson syndrome
- Dyskeratosis congenita (DC)[2]
- Cartilage-hair hypoplasia (CHH)
- Infections: Parvovirus B19, HIV, Viral hepatitis
- Drugs and toxins (eg. antileptic drugs, azathioprine)
- Immune-mediated disorders( eg Thymoma, Myasthenia Gravis, SLE)
Epidemiology and Demographics
- Classical Diamond-Blackfan anemia (DBA) affects about seven per million live births per year. Thus in the United States, with 4 million live births per year, each year approximately 25-35 new patients will be diagnosed.[3]
- male-to-female ratio of cases is approximately 1:1 despite rare cases of X-linked inheritance
Risk Factors
Natural History, Complications and Prognosis
Natural history
Classic DBA:
- The symptomatic onset of Diamond black-fan anemia becomes apparent during the first year of life.
- Symptoms of anemia include fatigue, weakness, and an abnormally pale appearance (pallor).
- Approximately half of DBA cases have physical abnormalities.
- The severity of Diamond-Blackfan anemia may vary, even within the same family. individuals with "non-classical" Diamond-Blackfan anemia with less severe symptoms have been identified. For example, some affected individuals have mild anemia beginning later in childhood or in adulthood, while others have some of the physical features but no bone marrow problems.
Non-classic DBA:
- presents with mild or absent anemia with only subtle indications of erythroid abnormalities such as macrocytosis, elevated eADA, and/or elevated HbF concentration
- Onset later in life
- Congenital anomalies or short stature consistent with DBA and minimal or no evidence of abnormal
Complications
- Common complications of Diamond black-fan include:
- Physical abnormalities
- higher-than-average chance of developing myelodysplastic syndrome (MDS), acute myeloid leukemia (AML) bone cancer (osteosarcoma), colon cancer
- Eye problems such as cataracts, glaucoma, or strabismus
- kidney abnormalities
- hypospadias
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
- The diagnosis is established when all four of the following diagnostic criteria are present:[3][5]
- Age younger than one year
- Macrocytic anemia with no other significant cytopenias
- Reticulocytopenia
- Normal marrow cellularity with a paucity of erythroid precursors
History
- DBA typically presents in infancy, most commonly with pallor and lethargy, median age at presentation is 8 weeks, with a median age at diagnosis of 12 weeks. Hydrops fetalis in some cases
- Family history of DBA consistent with autosomal dominant inheritance
symptoms
- Symptoms of anemia include pallor, irritability, failure to thrive, sleepiness, irritability, poor appetite, and weakness[1]
- Growth retardation (in about 30% )
- Congenital malformations, in particular craniofacial, upper-limb, heart, and genitourinary malformations:(observed in ~30%-50%):
- microcephaly
- low frontal hairline
- wide-set eyes (hypertelorism)
- droopy eyelids (ptosis)
- broad, flat bridge of the nose
- small, low-set ears
- small lower jaw (micrognathia)
- cleft palate
- cleft lip
- short, webbed neck
- Smaller and higher shoulder blades than usual
- malformed or absent thumbs
Treatment
Medical Therapy | Surgery | Cost-Effectiveness of Therapy | Future or Investigational Therapies
Case Studies
External Links
- ↑ 1.0 1.1 1.2 1.3 1.4 Da Costa L, Narla A, Mohandas N (2018). "An update on the pathogenesis and diagnosis of Diamond-Blackfan anemia". F1000Res. 7. doi:10.12688/f1000research.15542.1. PMC 6117846. PMID 30228860.
- ↑ 2.0 2.1 Alter BP (November 2017). "Inherited bone marrow failure syndromes: considerations pre- and posttransplant". Blood. 130 (21): 2257–2264. doi:10.1182/blood-2017-05-781799. PMC 5714231. PMID 29167174.
- ↑ 3.0 3.1 Vlachos A, Ball S, Dahl N, Alter BP, Sheth S, Ramenghi U, Meerpohl J, Karlsson S, Liu JM, Leblanc T, Paley C, Kang EM, Leder EJ, Atsidaftos E, Shimamura A, Bessler M, Glader B, Lipton JM (September 2008). "Diagnosing and treating Diamond Blackfan anemia: results of an international clinical consensus conference". Br. J. Haematol. 142 (6): 859–76. doi:10.1111/j.1365-2141.2008.07269.x. PMC 2654478. PMID 18671700.
- ↑ Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean L, Stephens K, Amemiya A, Clinton C, Gazda HT. PMID 20301769. Vancouver style error: initials (help); Missing or empty
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(help) - ↑ Vlachos A, Muir E (November 2010). "How I treat Diamond-Blackfan anemia". Blood. 116 (19): 3715–23. doi:10.1182/blood-2010-02-251090. PMC 2981532. PMID 20651069.
- ↑ Da Costa L, Chanoz-Poulard G, Simansour M, French M, Bouvier R, Prieur F, Couque N, Delezoide AL, Leblanc T, Mohandas N, Touraine R (February 2013). "First de novo mutation in RPS19 gene as the cause of hydrops fetalis in Diamond-Blackfan anemia". Am. J. Hematol. 88 (2): 160. doi:10.1002/ajh.23366. PMID 23349008.
- ↑ Wlodarski MW, Da Costa L, O'Donohue MF, Gastou M, Karboul N, Montel-Lehry N, Hainmann I, Danda D, Szvetnik A, Pastor V, Paolini N, di Summa FM, Tamary H, Quider AA, Aspesi A, Houtkooper RH, Leblanc T, Niemeyer CM, Gleizes PE, MacInnes AW (June 2018). "Recurring mutations in RPL15 are linked to hydrops fetalis and treatment independence in Diamond-Blackfan anemia". Haematologica. 103 (6): 949–958. doi:10.3324/haematol.2017.177980. PMC 6058779. PMID 29599205.