Diamond-Blackfan anemia overview: Difference between revisions
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[[Renal]] [[ultrasound]] and [[echocardiography]] should be done to diagnosis any renal or cardiac abnormalities. | |||
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Revision as of 22:17, 7 August 2020
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]
Overview
Diamond-Blackfan anemia (DBA) is a congenital erythroid aplasia that usually presents in infancy.The classic form is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets. About half of the affected patients have congenital malformations, and growth retardation in 30% of affected individuals. The symptoms and physical findings associated with DBA vary greatly from person to person.The hematologic complications occur in 90% of affected individuals during the first year of life.[1]
Historical Perspective
Diamond and Blackfan described congenital hypoplastic anemia in 1938. In 1951, responsiveness to corticosteroids was reported. In 1961, Diamond and colleagues presented longitudinal data on 30 patients and noted an association with skeletal abnormalities. In 1997 a region on chromosome 19 was determined to carry a gene mutated in DBA. In 1999, mutations in the ribosomal protein S19 gene (RPS19) were found to be associated with disease in some of the patients. In 2001, it was determined that a second DBA gene lies in a region of chromosome 8. In 2007, Furthermore, mutations in large ribosomal subunit-associated proteins rpl5, rpl11, and rpl35a, have been described. In 2010, 10 additional DBA genes are identified. Non-RP gene, GATA1, was identified in 2012. The largest study to date, provides a genetic explanation for nearly 80 percent of patients. Researchers still want to know why steroids often work in DBA, find more mutations, and address some questions about Diamond-Blackfan anemia.
Classification
Based on diagnostic criteria established by an International Consensus Conference.1 A diagnosis of classical DBA is made in the presence of all the diagnostic criteria and a diagnosis of non-classical DBA in the presence of i) 3 diagnostic criteria and one major supporting criterion or 2 minor criteria; ii) 2 diagnostic criteria and 3 minor supporting criteria; iii) 2 major supporting criteria, even in the absence of diagnostic criteria.
Pathophysiology
DBA has revealed itself as a "Ribosomapathy. Mutations in ribosomal protein genes have been confirmed to be the direct cause of faulty erythropoiesis and anemia.DBA mutations reduce the actual numbers of ribosomes in blood precursor cells. Without enough ribosomes, the precursors can’t produce enough GATA1, so mature red cells never form. Other blood cells — like platelets, T cells, and B cells — are not affected since they’re not dependent on GATA1. Based on a documented pathogenetic hypothesis which has been named " ribosomal stress ", ultimately a defective ribosome biosynthesis leads to apoptosis in those defective erythroid progenitors which in turn is leading to erythroid failure. In ‘‘ribosomal stress, reduced RP synthesis activates p53 that induces the downstream events and leads to cell cycle termination or apoptosis, leading to erythroid failure.
Causes
About 80%-85% of the affected patients have been found to have a heterozygous mutation in a gene encoding a small (RPS7, RPS10, RPS15A, RPS17, RPS19, RPS20, RPS24, RPS26, RPS27 RPS28, RPS29) or large (RPL5, RPL11, RPL15, RPL17, RPL19, RPL26, RPL27, RPL31 RPL35A) ribosomal subunit-associated protein. In the remaining 10-15% of DBA cases, no abnormal genes have yet been identified. It is likely that mutations are in a regulatory region including intronic regions and promoters in one of the known RP genes and may account for the DBA phenotype.
Differentiating Diamond Black-fan Anemia from Other Diseases
Diamond Black-fan Anemia must be differentiated from other diseases that cause Anemia and bone marrow failure such as Aplastic anemia, Fanconi anemia, Transient Erythroblastopenia of Childhood, Shwachman-Diamond syndrome, Pearson syndrome, Dyskeratosis congenita, Cartilage-hair hypoplasia, Congenital amegakaryocytic thrombocytopenia, Infections: Parvovirus B19, HIV, Viral hepatitis, Drugs, and toxins (eg. antileptic drugs, azathioprine), Immune-mediated disorders( eg Thymoma, Myasthenia Gravis, SLE)
Epidemiology and Demographics
Risk Factors
Screening
Natural History, Complications, and Prognosis
Diagnosis
Diagnostic Study of Choice
History and Symptoms
Physical Examination
Laboratory Findings
Electrocardiogram
X-ray
Echocardiography and Ultrasound
Renal ultrasound and echocardiography should be done to diagnosis any renal or cardiac abnormalities.
CT scan
MRI
Other Imaging Findings
Other Diagnostic Studies
Treatment
Medical Therapy
Interventions
Surgery
Primary Prevention
Secondary Prevention
References