Definition A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. [uniprot.org]

Case 1 Case 2 Case 3 Case 4 Case 5 Case 6 Age at presentation (mo) 7 8 10 18 7 10 Age of 1st symptom (mo) 2 2.5 2.5 3 4 2 Gender Male Male Male Female Female Male Pallor Present Present Present Present Present Present Congenital anomalies Absent Absent [indianpediatrics.net]

It commonly presents with congenital bony malformations (50% of the cases) and growth retardation (30% of cases).[3] The median age of presentation and diagnosis is 2 months of age.[2][3] Children usually first present with lethargy and pallor. [statpearls.com]

Presentation[1] The severity of symptoms is variable but is often severe and life-threatening. Usually it presents in the first few months of life when a young child develops a severely hypoplastic macrocytic anaemia. [patient.info]

• Anemia

  Definition A form of Diamond-Blackfan anemia, a congenital non-regenerative hypoplastic anemia that usually presents early in infancy. [uniprot.org]

  […] erythroid progenitors in the bone marrow (OMIM: Diamond-Blackfan Anemia 1) Predisposition to acute myelogenous leukemia, myelodysplastic syndrome and solid tumors Essential features Also known as Blackfan-Diamond anemia, congenital hypoplastic anemia [pathologyoutlines.com]

  Ribosomal protein S24 gene is mutated in Diamond-Blackfan anemia. American Journal Of Human Genetics. 2006 79(6):1110-8.17186470. Boria et al. The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update. [genedx.com]

  Test Catalog Invitae Diamond-Blackfan Anemia Panel Test description The Invitae Diamond-Blackfan Anemia Panel analyzes genes associated with Diamond-Blackfan anemia (DBA). [invitae.com]

• Pallor

  Pallor and dyspnea, especially during feeding or while sucking, are the principal warning signs. Pallor is isolated, without organomegaly, signs suggestive of hemolysis or involvement of other hematopoietic cell lines. [orpha.net]

  All had severe pallor at presentation, with mild hepato-megaly and just palpable spleen in one child. Thumb anomaly was present in one of them. [indianpediatrics.net]

  Presenting features in infants are pallor and dyspnea mainly whilst feeding or sucking. [cags.org.ae]

  RPS26, RPS27, RPS29, RPL5, RPL11, RPL15, RPL26, RPL27, RPL31, RPL35A (Br J Haematol 2016;172:782) Diagrams / tables Images hosted on other servers: Hypothetic model for abortive ribosome assembly and p53 activation relevant to DBA Clinical features Pallor [pathologyoutlines.com]

  Red blood cells carry oxygen throughout the body, so a child with DBA may have symptoms related to a deficit of blood oxygen (anemia), including: Pallor (paleness) Irregular heartbeat, due to the heart trying to keep oxygen moving throughout the body [verywellhealth.com]

• Dysostosis

  Malformations are seen more frequently with DBA6 RPL5 and DBA7 RPL11 mutations.[5] The genetic abnormalities underpinning the combination of DBA with Treacher Collins syndrome (TCS)/mandibulofacial dysostosis (MFD) phenotypes are heterogeneous, including [en.wikipedia.org]

• Coarctation of the Aorta

  Congenital heart disease (CHD) in Diamond Blackfan anemia (DBA).A, The CHD anomalies in the Diamond Blackfan Anemia Registry (DBAR) included ventricular septal defect (VSD; 44%), atrial septal defect (ASD; 32.5%), coarctation of the aorta (CoA; 4.4%), [ahajournals.org]

  ventricular septal defects, atrial septal defects, coarctation of the aorta, tetralogy of Fallot) and genitourinary track (e.g., absent kidney, horseshoe kidney and hypospadias). [cancertherapyadvisor.com]

• Dyspnea

  Presenting features in infants are pallor and dyspnea mainly whilst feeding or sucking. [cags.org.ae]

  Pallor and dyspnea, especially during feeding or while sucking, are the principal warning signs. Pallor is isolated, without organomegaly, signs suggestive of hemolysis or involvement of other hematopoietic cell lines. [orpha.net]

• Heart Disease

  Congenital heart disease (CHD) is one of the most commonly occurring congenital anomalies in the general population. [ahajournals.org]

  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. [rarediseases.org]

  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 [f1000research.com]

• Thrombosis

  […] with recombinant Interleukin 3 (IL3), a stimulator of erythropoiesis at the stem cell level, has been studied very extensively in DBA in the past, but was eventually discarded due to conflicting results and undesired side effects, such as deep venous thrombosis [onlinelibrary.wiley.com]

Laboratory workup is significant for elevated MCV and erythrocyte adenosine deaminase (eADA). [statpearls.com]

• Macrocytic Anemia

  Definition / general A member of the inherited bone marrow failure syndromes (BMFS); typically shows an onset in the first year of life (Br J Haematol 2016;172:782) Main features include normochromic macrocytic anemia, reticulocytopenia and nearly absent [pathologyoutlines.com]

  The main features are normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. [malacards.org]

  Diamond-Blackfan anemia is characterized by a moderate to severe macrocytic anemia, erythroblastopenia, and an increased risk of malignancy. 30 to 40% of Diamond-Blackfan anemia patients present with short stature and congenital anomalies, the most frequent [uniprot.org]

  Children with DBA will likely have a macrocytic anemia, normal neutrophils and platelets, a very low to absent reticulocyte count, elevated hemoglobin F and increased eADA activity. [cancertherapyadvisor.com]

• Cytopenia

  […] criteria and three minor criteria A positive family history and three minor criteria Nonclassical DBA is diagnosed when there is a DBA associated gene mutation but insufficient diagnostic criteria Laboratory Macrocytic anemia with no other significant cytopenias [pathologyoutlines.com]

  Over the next 2 years, she developed progressive fatigue and cytopenias. One month before presentation, a blood count showed a hemoglobin level of 5.6 g/dL, a platelet count of 91 103/μL, and a WBC count of 3.0 103/μL. [ascopubs.org]

  In rare cases, aplastic anemia, multilineage cytopenia, or leukemia have been clinical features. [statpearls.com]

  However, not all DBA patients present with severe anaemia at a very young age, and cytopenias in other lineages (and no signs of MDS/AML) have been described. [onlinelibrary.wiley.com]

  All of them had macrocytic or normocytic anemia with reticulo-cytopenia, and bone marrow examination revealed marked erythroid hypoplasia. All of them were treated with oral steroids with a good response. [indianpediatrics.net]

• Macrocytosis

  Macrocytosis, elevated fetal hemoglobin and increased eADA. Physical abnormalities in about 40% of DBA cases including craniofacial and thumb abnormalities, atrial or ventrucular septal defects, short stature, mild retardation, etc. [atlasgeneticsoncology.org]

  […] with complete atrioventricular canal with double outlet right ventricle, respectively, were found to have elevated erythrocyte adenosine deaminase activity (range, 1.01–1.35 EU/gm Hb; normal, 0.33–0.96) characteristic of DBA.4 None of the patients had macrocytosis—a [ahajournals.org]

  Features that support a diagnosis of DBA include the presence of congenital abnormalities, macrocytosis, elevated fetal hemoglobin, and elevated adenosine deaminase levels in red blood cells.[21] Most patients are diagnosed in the first two years of life [en.wikipedia.org]

Besides the patients who are on steroid treatment are also prone to hepatic iron laoding. [library.ehaweb.org]

What are the treatment options for Diamond-Blackfan anemia? Corticosteroids Corticosteroid treatment in the form of oral prednisone is usually the first treatment option. [my.clevelandclinic.org]

Management and treatment The two main therapeutic approaches are regular transfusions and long-term corticosteroid therapy. Treatment must be adapted to each case and according to the age of the patient. [orpha.net]

No study has ever combined these two drugs for the treatment of DBA. This study is designed to explore the combined use of ATG and cyclosporine as a rational approach to the treatment of DBA. [clinicaltrials.gov]

Our patients have access to advanced diagnosis and treatments, including DNA mutation identification and ongoing clinical trials investigating new treatments. [childrenshospital.org]

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]

Diamond-Blackfan Anemia) Increased red cell mean corpuscular volume (MCV) Reticulocytopenia Elevated erythrocyte adenosine deaminase activity (eADA) (observed in 80% - 85%) Elevated hemoglobin F (HbF) concentration Prognostic factors Associated with unfavorable prognosis [pathologyoutlines.com]

Prognosis: there are no genotype–phenotype correlations that are predictive of prognosis, that is, response to corticosteroid therapy, likelihood of remission, cancer predisposition (occurrence or type of cancer) or life expectancy. [nature.com]

[…] respond to steroids or blood transfusions.[13] Complications Side-effects from long-term steroids and iron overload associated with repeated blood transfusions.[11] There is an increased risk of malignancies, including solid tumours and leukaemias.[6, 14] Prognosis [patient.info]

Prognosis is relatively good, but complications related to treatment may alter the patient's quality of life.[2] Severe complications as a result of treatment or the development of cancer may reduce life expectancy.[2] Disease severity is determined [statpearls.com]

Detailed Description: Diamond Blackfan anemia (DBA) is a constitutional pure red cell aplasia of unknown etiology. There is laboratory evidence for an immune mechanism and most patients respond to corticosteroids. [clinicaltrials.gov]

Etiology At present, disease-causing mutations are identified in 40-45% of patients. All involved genes code for ribosomal proteins (RPs) from either the small (RPS7, RPS17, RPS19, RPS24) or the large (RPL5, RPL11, RPL35a) ribosomal subunit. [orpha.net]

No extrinsic etiologic mechanisms were identified. Evidence of anemia was long-standing and varied in severity. [amjmed.com]

Iron deficiency anemia is the most common type of anemia worldwide in all the age groups.[1] However, here we talk about a rare type of anemia with genetic etiology. [statpearls.com]

The Drug Etiology of Agranulocytosis and Aplastic Anemia. New York: Oxford University Press; 1991. Issaragrisil S, Sriratanasatavorn C, Piankijagum A, Vannasaeng S, Porapakkham Y, Leaverton PE, et al. Incidence of aplastic anemia in Bangkok. [medscape.com]

Summary Epidemiology Annual incidence in the general population of Europe is estimated at around 1/150,000. Both sexes are equally affected and no ethnic predisposition has been identified. [orpha.net]

Normochromic macrocytic anemia, reticulocytopenia, normocellular for age marrow and nearly absent erythroid progenitors in the bone marrow (OMIM: Diamond-Blackfan Anemia 1) Predisposition to acute myelogenous leukemia, myelodysplastic syndrome and solid tumors Epidemiology [pathologyoutlines.com]

[…] cases are sporadic, approximately 10-25% are familial, with most showing autosomal dominant inheritance.[4] Leukocyte and platelet counts are normal or slightly reduced.[5] The exact cause is not clear but there is a disorder of ribosome biogenesis.[6] Epidemiology [patient.info]

PMID 17151020 The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia. [atlasgeneticsoncology.org]

The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond Blackfan anemia. J Pediatr Hematol Oncol 2001; 23: 377-382. 4. Dianzani I, Garelli E, Ramenghi U. Diamond-Blackfan Anemia: an overview. [indianpediatrics.net]

This review will focus on the diagnosis of DBA along with a description of new advances in our understanding of the pathophysiology and treatment recommendations for DBA. [f1000research.com]

Shimamura A, Alter BP: Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev 24:101-122, 2010 Crossref, Google Scholar 20. [ascopubs.org]

[…] tumors Epidemiology Incidence 1:100,000 1:200,000 live births and remains consistent across ethnicities (GeneReviews: Diamond-Blackfan Anemia) Males and females equally affected 90% diagnosed within first year of life and 35% diagnosed within first month Pathophysiology [pathologyoutlines.com]

Despite significant progress in defining the molecular basis of DBA and increased understanding of the mechanistic basis for DBA pathophysiology, progress in developing new therapeutic options has been limited. [pubmed.ncbi.nlm.nih.gov]

Join our weekly wellness digest from the best health experts in the business Ellis SR; Nucleolar stress in Diamond Blackfan anemia pathophysiology. Biochim Biophys Acta. 2014 Jun1842(6):765-8. doi: 10.1016/j.bbadis.2013.12.013. Epub 2014 Jan 8. [patient.info]

MRI can be used as a non-invasive tool to recognize pituitary IOL and identification of proper chelation therapy for the prevention of irreversible pituitary tissue damage. [abstracts.eurospe.org]

Patients with DBA should be screened for iron loading as early as possible and chelation treatment should be initiated to prevent the related morbidity and mortalities. Session topic: 12. Bone marrow failure syndromes incl. [library.ehaweb.org]

How can Diamond-Blackfan anemia be prevented? As with most genetic diseases, there are no known methods to prevent the disease. [cancertherapyadvisor.com]

A regular check of Hb levels may be recommended. 3.2.1 Will the result of a genetic test influence lifestyle and prevention? If the test result is positive (please describe): Yes. [nature.com]

It is advised to carefully taper low maintenance doses to prevent overshooting the individual minimal effective dose. [onlinelibrary.wiley.com]