|Year : 2020 | Volume
| Issue : 2 | Page : 163-170
Diamond–Blackfan anemia with mutation in RPS19: A case report and an overview of published pieces of literature
Dilshad Jahan1, Md Maruf Al Hasan1, Mainul Haque2
1 Department of Hematology, Apollo Hospitals, Dhaka, Bangladesh
2 Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kuala Lumpur, Malaysia
|Date of Submission||20-Oct-2019|
|Date of Decision||20-Feb-2020|
|Date of Acceptance||21-Feb-2020|
|Date of Web Publication||15-Apr-2020|
Prof. Mainul Haque
Unit of Pharmacology, Faculty of Medicine and Defence Health, Universiti Pertahanan Nasional Malaysia (National Defence University of Malaysia), Kem Sungai Besi 57000, Kuala Lumpur.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Introduction: Diamond–Blackfan anemia (DBA), one of a rare group of inherited bone marrow failure syndromes, is characterized by red cell failure, the presence of congenital anomalies, and cancer predisposition. It can be caused by mutations in the RPS19 gene (25% of the cases). Methods: This case report describes a 10-month-old boy who presented with 2 months’ history of gradually increasing weakness and pallor. Results: The patient was diagnosed as a case of DBA based on peripheral blood finding, bone marrow aspiration with trephine biopsy reports, and genetic mutation analysis of the RPS19 gene. His father refused hematopoietic stem cell transplantation for financial constraints. Patient received prednisolone therapy with oral folic acid and iron supplements. Conclusion: Hemoglobin raised from 6.7 to 9.8g/dL after 1 month of therapeutic intervention.
Keywords: Diamond–Blackfan anemia, hematopoietic stem cell transplantation, RPS19 gene, Prednisolone, Bone Marrow, Anemia, Genetic and Rare Disease
|How to cite this article:|
Jahan D, Al Hasan MM, Haque M. Diamond–Blackfan anemia with mutation in RPS19: A case report and an overview of published pieces of literature. J Pharm Bioall Sci 2020;12:163-70
|How to cite this URL:|
Jahan D, Al Hasan MM, Haque M. Diamond–Blackfan anemia with mutation in RPS19: A case report and an overview of published pieces of literature. J Pharm Bioall Sci [serial online] 2020 [cited 2022 Jul 6];12:163-70. Available from: https://www.jpbsonline.org/text.asp?2020/12/2/163/282491
| Introduction|| |
“Diamond–Blackfan anemia (DBA; Mendelian Inheritance in Man #105650), one of a rare group of inherited bone marrow failure syndromes (IBMFSs), is characterized by red cell failure, the presence of congenital anomalies, and cancer predisposition.” DBA is also characterized as a developing cluster of illnesses identified as ribosomopathies., DBA is a scarce inherited diverse clinical and genetic erythroblastopenia because IBMFS resulted in red cell aplasia with physical malformations.
| Review of Literatures|| |
DBA was first stated in 1936 by Dr. Hugh W. Josephs of Johns Hopkins University, Maryland, USA. Later, in 1938, a more detailed description was given by Dr. LK Diamond and Dr. KD Blackfan; initially, it was considered as congenital hypoplastic anemia. The diagnostic principles for DBA were published in 1976 and continued as an acceptable standard.,, DBA initially presented with anemia before the age of 12 months. The signs include either typical or a little reduced neutrocytes counts, inconstant platelet counts, reticulocytopenia, macrocytosis, and healthy bone marrow cellularity with a scantiness of red cell precursors.
The molecular biology of DBA is comprehensively researched, and, in more than 50% of cases, the syndrome appears to result from haploinsufficiency of either a small or large subunit-associated ribosomal protein (RP)., However, the exact process by which RP haploinsufficiency consequences in erythroid failure, in addition to the other clinical symptoms and signs, remains indeterminate. Macrocytic anemia is a protuberant characteristic of DBA, but the illness is also pigeonholed by physical developmental impedance, and at least 40% of DBA cases had inherited incongruities. DBA is correlated with single, monoallelic, and inactivating mutations in RP genes. In DBA, modifications or bulky deletions in RP genes include RPS7, RPS10, RPS17, RPS19, RPS24, RPS26, RPL5, RPL11, RPL26, and RPL35A. These mutations have been confirmed by approximately 60% of DBA patients. Additionally, multiple studies revealed that equally have large and small subunits of RP genetic inconsistencies observed in RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26, but also affects and mutated many other genes.,, Furthermore, several research studies reported that outlying cases and families of DBA been recognized with an increased number of mutated RPs genes, which include RPL3, RPL7, RPL9, RPL14, RPL19, RPL23A, RPL26, RPL35, RPL36, RPS8, RPS15, RPS27A, RPL18, and RPL35.,, The molecular pathology of DBA has been extensively studied in the last few years. These research studies revealed that the cause for the anemia observed in both DBA and in del (5q) myelodysplastic syndrome is haploinsufficiency of RPs,,, leading to nucleolar function, translational surveillance, erythroid failure, cancer predisposition, and physical disabilities.,,
The diagnostic principles have extended intensely as a result of detail insight of gene and upgraded data regarding DBA epidemiology.,, The frequency of DBA is about six per million live birth. DBA usually presents around the age of 1 year with “macrocytic, or occasionally normocytic, anemia with reticulocytopenia, essentially normal neutrophil and platelet counts, and a normocellular bone marrow with a lack of erythroid precursors.” Research studies showed that 25% of the DBA cases are associated with a mutation in the RPS19 gene.,, Other studies showed that approximately 43% of patients with DBA are related to mutations in six more RP genes including RPS24, RPS17, RPL35A, RPL5, RPL11, and RPS7. Many nonclassic patients of DBA have been recognized. These pediatric cases often have mild blood-related disorders or DBA-associated hereditary abnormalities or totally healthy. Furthermore, patients with DBA sometimes present beyond 1 year of age into late childhood, adolescence, or even adulthood.,, The number of autosomal-dominant recessive inherited patients has been assessed, for at least one genotype, to be approximately 45%, with the recognition of these non-classic DBA phenotypes.,
The preliminary laboratory investigations regarding DBA diagnosis comprise a total “blood count, reticulocyte count, and if possible, fetal hemoglobin (HbF) level and an erythrocyte adenosine deaminase (eADA) activity.” Patients with DBA who possess repeatedly physical abnormalities or family history of physical deformities, found to have hypoproliferative anemia, unclarified macrocytosis, raised HbF, and even devoid of anemia, should be inquired further., Most of the patients with DBA have macrocytosis, with an elevation in HbF., A bone marrow aspirate is required for diagnosis of DBA and usually shows a normocellular marrow with normal myeloid maturation, adequate megakaryocytes, and a discerning deficient of red cell precursors. A bone marrow histopathology is likewise suggesting considering cellularity. Cellularity has been noted to decrease inexplicably to the usual age-related decrement. A routine karyotype is necessary to identify any significant chromosomal abnormalities. Indeed, two of the “DBA genes” have been identified through the evaluation of a translocation involving the gene encoding RPS19 and a large deletion on chromosome 3q involving the coding region for RPL35a, respectively. Although not pronounced, the presentation of this disease in childhood is conceivable. If the bone marrow morphology is unswerving with giant, multinucleated erythroblasts and pronormoblasts, or if there is no genetic indication supportive of the diagnosis of DBA, predominantly in atypical presentations, viral titers and assessment for viral genome are carried out to rule out parvovirus B19 as the reason.,,
Inherited bone marrow failure syndromes
The clear understanding of molecular pathogenesis of IBMFS is essentially and urgently required for proper diagnosis and treatment, although these disease incidence rate is quite low. IBMFS patients often have several complications, involving many major systems. Hematopoietic stem cell transplantation (SCT) resolves some issues, avert others, but causes some new pathology. Quite a few propositions have appeared within each subcategory of IBMFS including the ribosomopathies that comprise both ribosome assembly and ribosomal ribonucleic acid (RNA) processing. A recent study reported that ribosomopathies are involved in DBA, Fanconi anemia (FA), Shwachman–Diamond–Bodian syndrome (SDBS), dyskeratosis congenita (DC), and cartilage hair hypoplasia. These all disease conditions have mutations in RPs and in proteins responsible for processing of ribosomal RNA. The respective pathologic pathways involve deoxyribonucleic acid (DNA) repair (FA), telomere biology (DC), and ribosome biogenesis (DBA and SDS)., A lot of patients with IBMFS present with hematologic symptoms and signs, such as single-cell or pancytopenia, MDS, or leukemia, particularly acute myeloid leukemia (AML). The diagnosis of an IBMFS often exposed during assessment for the hematologic indexes, due to the reflection of specific clinical phenotypes or screening tests for syndrome-specific or genomic studies., The principal diagnostic feature for FA includes increased chromosome breakage in lymphocytes cultured with a DNA cross-linker; for DC it includes short telomeres by lymphocyte flow cytometry and fluorescent in situ hybridization; for DBA it includes elevated red cell adenosine deaminase; and for SDS it includes low levels of serum trypsinogen and isoamylase.,,,
Three hundred fifty-four DBA patients’ were enrolled in the Diamond Blackfan Anemia Registry of North America (DBAR) in 2001, and another research study reported additional six hundred DBA patients’ were registered by 2012. DBAR was commenced in 1991 for a wide-ranging evaluation of the clinical epidemiology and pathophysiology of DBA. The DBAR is a professional and charitable organization that registered patients after necessary informed consent is obtained in agreement with the Helsinki Declaration.
Morbidity, mortality, and treatment options
Multiple studies from several countries showed that approximately 40% of patients with DBA were transfusion-dependent as these cases were not responding to corticosteroids, although 40% were corticosteroid-dependent and 20% were transfusion-independent with additional medication.,, A group of patients improved and maintained adequate hemoglobin levels with initial corticosteroid therapy. Nonetheless, a small number of patients do not respond to corticosteroid, and remission occurs after prolonged blood transfusion. The DBAR defines “remission” as a stable, physiologically acceptable hemoglobin, lasting for at least 6 months, independent of corticosteroids, transfusions, or other therapy. Among DBA cases, 72% of them had remission within the first 10 years of life, and the majority have remission maintained, and 20% DBA cases have remission by the age of 25 years., Nevertheless, among pregnant woman hormonal stress increases and contributes as a significant aspect for relapse, which usually fades away after childbirth. Although the cancer risk among patients with DBA is quite low, approximately 4.14% (29 patients of 700 DBA cases) develop AML., The median age for the development of cancer among DBA cases was 15 years (range 1–43 years), considerably earlier than the median of 68 years in the general population. Glucocorticoids persist for almost 70 years, as the primary choice of treatment for DBA. Although glucocorticoid efficacy regarding the management of DBA was first described in 1951, the mechanism of action glucocorticoids in DBA is still shadowy and under search. Nonetheless, approximately 80% of patients with DBA improve to a preliminary treatment schedule of glucocorticoids.,
Researchers relentlessly work to develop more effective and safer alternative medicine to cure DBA. Thereafter, several new therapeutic alternative appear in the market including high-dose corticosteroids,, intravenous immunoglobulin,, high-dose erythropoietin, interleukin-3,,,, and androgens. Immunosuppressive therapy with cyclosporine A has been investigated in patients with DBA with no theoretic origin. Consequently, the efficacy of cyclosporine A in the treatment of DBA was not well established.,, In the treatment of DBA the efficacy of antithymocyte globulin had not obtained much successful intervention. Another study showed metoclopramide (a dopamine antagonist) to be effective at least 33% to produce hematologic response among DBA cases. It is believed that metoclopramide encourages the release of prolactin from the pituitary gland, and prolactin possibly recovers and expands erythropoiesis. Nevertheless, such positive findings of erythropoiesis were not observed in research studies in the USA and Europe. These studies found only a 10% improvement., Recent studies used in limited scale leucine and lenalidomide for DBA and had remission.
| Case Report|| |
A 10-month-old male baby named Rafi Hossain, with his father, attended a district-level hospital, Borura, Comilla, Bangladesh, with 2 months’ history of gradually increasing weakness and pallor. Complete blood count showed severe anemia, treated with iron therapy and blood transfusion. There was no improvement, and the baby again developed weakness and pallor; repeat complete blood count showed severe anemia, treated with red blood cell transfusion. As there was no improvement, baby with his father came to hematology outpatient department in Apollo Hospitals, Dhaka, Bangladesh on June 27, 2019 (patient ID: Apollo UHID 842273). The baby had one elder brother who was 13 years old and led a healthy life. There was no history of consanguinity. On examination, he was severely anemic, but there was no icterus. The baby weighted 9kg, pulse 150 beats/min, temperature 97°C, and respiration 24 breaths/min. Complete blood count showed hemoglobin 5.6g/dL, hematocrit 16.6%, mean corpuscular volume 77.9 fL, mean corpuscular hemoglobin 26.3 pg, and mean corpuscular hemoglobin concentration 33.7%. Total leukocyte count was 11.82 × 109/L and platelet count was 401 × 109/L. Peripheral blood film showed normocytic anemia [Figure 1] with eosinophilia. Hemoglobin electrophoresis showed HbA: 80.04%; HbE: 16.60%; and HbF: 3.36%. The red cells were normocytic, and HbE was increased. These two findings can be attributed to the patient receiving 11 units of packed red blood cell transfusions before coming to our hospital, and because of the same reason research team could not perform erythrocyte adenosine deaminase (eADA) estimation. Reticulocyte count was 0.24%. Bone marrow aspiration showed suggestive of pure red cell aplasia [Figure 2]. Erythropoiesis markedly depressed with the block in maturation, and occasional proerythroblasts were observed. Bone marrow trephine biopsy showed normocellular marrow with consistent with significantly depressed erythropoiesis. This patient has karyotype 46, XY. Polymerase chain reaction (PCR) for viral DNA showed negative of parvovirus B19, cytomegalovirus, Epstein–Barr virus, Herpes simplex virus 1 and 2, Varicella-zoster virus, enterovirus, and human herpesvirus 6 and 7. Direct coombs test was negative and lactate dehydrogenase 305 U/L. Findings of serum iron profile, liver function, and renal function tests were normal. Chest X-ray, echocardiogram, and ultrasonogram of the abdomen did not show any abnormality. The genetic study was performed for screening the mutations in the RPS19 gene of the baby. The genetic analysis was carried out in the Medgenome Labs, Bangalore, Karnataka, India, after obtaining the informed consent of the parents. The genetic study was conducted based on internationally reputed methods.,,,, The patient posses the frameshift mutations in intron 3 of the RPS19 gene [Figure 3]. Genetic study of patients’ parents could not be performed as they dissent. Parents’ argued they are having a healthy and quality life for so years. Thus, viewed they do not need such expensive laboratory test for their child trearment. Research team made a diagnosis of DBA since the baby presented with anemia at near 1 year of age, reticulocytopenia, normal white cell count and platelet counts, elevated HbF, and normal marrow cellularity with markedly depressed erythropoiesis, supporting criteria of gene mutation in RPS19 gene, PCR for viral DNA of parvovirus B19 not detected and there was no evidence of any other bone marrow failure syndrome. The research team could not consider the possibility of hemopoietic SCT due to their financial crisis. The baby was started on prednisolone therapy with oral folic acid and iron supplements. After 1 month, hemoglobin raised from 6.7 to 9.8g/dL., ,
| Discussion|| |
The current case of DBA primarily presented in district-level hospitals (secondary level public hospital) when the patient was in less than 1 year of age, later in specialized hospital reticulocytopenia, normal marrow cellularity with a lack of erythroid precursors and supporting criteria RPS19 mutation established the diagnosis of DBA. These findings were like studies and reports.,[21-23], Elevated levels of HbF and negative PCR for viral DNA of parvovirus B19 are supporting minor criteria. All the aforementioned criteria of the current case established that it was a nonclassical DBA. There are mounting pieces of evidence of diagnosing of the nonclassical presentation of DBA and generates more apprehension.,, In the current case, the focal evidence for the determination of DBA was the persistent isolated anemia, and normal marrow cellularity with markedly depressed erythropoiesis was in the same as mentioned earlier study report. DBA patients with late-onset anemia or a relatively mild course have been reported., Multiple previous studies showed that a meager number of patients were identified as DBA cases after 12 months of age, with insignificant anemia requiring treatment or intervention at all.,,[86-89] The present case, along with those previously reported, highlights the phenotypic heterogeneity of DBA and the prerequisite to contemplate this illness even in patients with no evident congenital glitches and only a distinctly drop of red cell precursors in the bone marrow., Incorporation of genetic studies assists an accurate diagnosis of patients with DBA, especially in cases with the nonclassical presentation.
| Conclusion|| |
To the best of our knowledge, this is probably the first case of DBA with RPS19 mutation confirmed by a genetic study in Bangladesh. The case had no physical abnormalities, but the detection of RPS19 mutation confirmed the diagnosis. This case reminds clinicians about DBA as a cause for anemia in infants and helps in further diagnosis of persistent isolated normocytic anemia of infants and children approximately 1 year of age.
Declaration of Patient Consent
The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given his consent for his images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published, and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Dianzani I, Loreni F. Diamond-Blackfan anemia: a ribosomal puzzle. Haematologica 2008;93:1601-4.
Danilova N, Gazda HT. Ribosomopathies: how a common root can cause a tree of pathologies. Dis Model Mech 2015;8:1013-26.
Nakhoul H, Ke J, Zhou X, Liao W, Zeng SX, Lu H. Ribosomopathies: mechanisms of disease. Clin Med Insights Blood Disord 2014;7:7-16.
Vlachos A, Ball S, Dahl N, Alter BP, Sheth S, Ramenghi U, et al
; Participants of Sixth Annual Daniella Maria Arturi International Consensus Conference. Diagnosing and treating Diamond Blackfan anaemia: results of an international clinical consensus conference. Br J Haematol 2008;142:859-76.
Shimamura A, Alter BP. Pathophysiology and management of inherited bone marrow failure syndromes. Blood Rev 2010;24:101-22.
Vlachos A, Muir E. How I treat Diamond-Blackfan anemia. Blood 2010;116:3715-23.
Josephs HW. Anemia of infancy and early childhood. Medicine 1936;15:307-451.
Diamond LK, Blackfan KD. Hypoplastic anemia. Am J Dis Child 1938;56:464-7.
Diamond LK, Wang WC, Alter BP. Congenital hypoplastic anemia. Adv Pediatr 1976;22:349-78.
Wang W, Nag S, Zhang X, Wang MH, Wang H, Zhou J, et al
. Ribosomal proteins and human diseases: pathogenesis, molecular mechanisms, and therapeutic implications. Med Res Rev 2015;35:225-85.
Toki T, Ito E. Molecular mechanisms underlying the pathology of Diamond-Blackfan anemia. Rinsho Ketsueki 2015;56:867-76.
Arbiv OA, Cuvelier G, Klaassen RJ, Fernandez CV, Robitaille N, Steele M, et al
. Molecular analysis and genotype-phenotype correlation of Diamond-Blackfan anemia. Clin Genet 2018;93:320-8.
Gazda HT, Sheen MR, Vlachos A, Choesmel V, O’Donohue MF, Schneider H, et al
. Ribosomal protein L5 and L11 mutations are associated with cleft palate and abnormal thumbs in Diamond-Blackfan anemia patients. Am J Hum Genet 2008;83: 769-80.
Errichiello E, Vetro A, Mina T, Wischmeijer A, Berrino E, Carella M, et al
. Whole exome sequencing in the differential diagnosis of Diamond-Blackfan anemia: clinical and molecular study of three patients with novel RPL5 and mosaic RPS19 mutations. Blood Cells Mol Dis 2017;64:38-44.
Gazda H, Landowski M, Buros C, Vlachos A, Sieff CA, Newburger PE, et al
. Array comparative genomic hybridization of ribosomal protein genes in Diamond-Blackfan anemia patients; evidence for three new DBA genes, RPS8, RPS14, and RPL15, with large deletion or duplication. Blood 2010;116:1007.
Mirabello L, Khincha PP, Ellis SR, Giri N, Brodie S, Chandrasekharappa SC, et al
. Novel and known ribosomal causes of Diamond-Blackfan anaemia identified through comprehensive genomic characterisation. J Med Genet 2017;54:417-25.
Narla A, Hurst SN, Ebert BL. Ribosome defects in disorders of erythropoiesis. Int J Hematol 2011;93:144-9.
Khanna-Gupta A. Bone marrow failure syndromes: the ribosomopathies. J Bone Marrow Res 2013;1:11752.
Yang Z, Guo Q, Wang Y, Chen K, Zhang L, Cheng Z, et al
. AZD3759, a BBB-penetrating EGFR inhibitor for the treatment of EGFR mutant NSCLC with CNS metastases. Sci Transl Med 2016;8:368ra172.
Mohammad AA. Myelodysplastic syndrome from theoretical review to clinical application view. Oncol Rev 2018;12:397.
Lipton JM. Diamond Blackfan anemia: new paradigms for a “not so pure” inherited red cell aplasia. Semin Hematol 2006;43:167-77.
Lipton JM, Ellis SR. Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis. Hematol Oncol Clin North Am 2009;23:261-82.
Lipton JM, Ellis SR. Diamond Blackfan anemia 2008–2009: broadening the scope of ribosome biogenesis disorders. Curr Opin Pediatr 2010;22:12-9.
Campagnoli MF, Garelli E, Quarello P, Carando A, Varotto S, Nobili B, et al
. Molecular basis of Diamond-Blackfan anemia: new findings from the Italian registry and a review of the literature. Haematologica 2004;89:480-9.
Draptchinskaia N, Gustavsson P, Andersson B, Pettersson M, Willig TN, Dianzani I, et al
. The gene encoding ribosomal protein S19 is mutated in Diamond-Blackfan anaemia. Nat Genet 1999;21:169-75.
Campagnoli MF, Ramenghi U, Armiraglio M, Quarello P, Garelli E, Carando A, et al
. RPS19 mutations in patients with Diamond-Blackfan anemia. Hum Mutat 2008;29:911-20.
Willig TN, Draptchinskaia N, Dianzani I, Ball S, Niemeyer C, Ramenghi U, et al
. Mutations in ribosomal protein S19 gene and Diamond Blackfan anemia: wide variations in phenotypic expression. Blood 1999;94:4294-306.
Doherty L, Sheen MR, Vlachos A, Choesmel V, O’Donohue MF, Clinton C, et al
. Ribosomal protein genes RPS10 and RPS26 are commonly mutated in Diamond-Blackfan anemia. Am J Hum Genet 2010;86:222-8.
West AH, Churpek JE. Old and new tools in the clinical diagnosis of inherited bone marrow failure syndromes. Hematol Am Soc Hematol Educ Program 2017;2017:79-87.
Bartels M, Bierings M. How I manage children with Diamond-Blackfan anaemia. Br J Haematol 2019;184:123-33.
Farrar JE, Dahl N. Untangling the phenotypic heterogeneity of Diamond Blackfan anemia. Semin Hematol 2011;48:124-35.
Ishii K, Young NS. Anemia of central origin. Semin Hematol 2015;52:321-38.
Mtatiro SN, Makani J, Mmbando B, Thein SL, Menzel S, Cox SE. Genetic variants at HbF-modifier loci moderate anemia and leukocytosis in sickle cell disease in Tanzania. Am J Hematol 2015;90:E1-4.
Alter BP, Rosenberg PS, Day T, Menzel S, Giri N, Savage SA, et al
. Genetic regulation of fetal haemoglobin in inherited bone marrow failure syndromes. Br J Haematol 2013;162:542-6.
Giri N, Kang E, Tisdale JF, Follman D, Rivera M, Schwartz GN, et al
. Clinical and laboratory evidence for a trilineage haematopoietic defect in patients with refractory Diamond-Blackfan anaemia. Br J Haematol 2000;108:167-75.
Zikidou P, Grapsa A, Bezirgiannidou Z, Chatzimichael A, Mantadakis E. Parvovirus B19-triggered acute hemolytic anemia and thrombocytopenia in a child with Evans syndrome. Mediterr J Hematol Infect Dis 2018;10:e2018018.
Lefrère JJ, Couroucé AM, Bertrand Y, Girot R, Soulier JP. Human parvovirus and aplastic crisis in chronic hemolytic anemias: a study of 24 observations. Am J Hematol 1986;23:271-5.
Chirnomas SD, Kupfer GM. The inherited bone marrow failure syndromes. Pediatr Clin North Am 2013;60:1291-310.
Alter BP. Inherited bone marrow failure syndromes: considerations pre- and posttransplant. Blood 2017;130:2257-64.
Narla A, Ebert BL. Ribosomopathies: human disorders of ribosome dysfunction. Blood 2010;115:3196-205.
Wegman-Ostrosky T, Savage SA. The genomics of inherited bone marrow failure: from mechanism to the clinic. Br J Haematol 2017;177:526-42.
Muramatsu H, Okuno Y, Yoshida K, Shiraishi Y, Doisaki S, Narita A, et al
. Clinical utility of next-generation sequencing for inherited bone marrow failure syndromes. Genet Med 2017;19:796-802.
Fargo JH, Rochowski A, Giri N, Savage SA, Olson SB, Alter BP. Comparison of chromosome breakage in non-mosaic and mosaic patients with Fanconi anemia, relatives, and patients with other inherited bone marrow failure syndromes. Cytogenet Genome Res 2014;144:15-27.
Alter BP, Baerlocher GM, Savage SA, Chanock SJ, Weksler BB, Willner JP, et al
. Very short telomere length by flow fluorescence in situ hybridization identifies patients with dyskeratosis congenita. Blood 2007;110:1439-47.
Fargo JH, Kratz CP, Giri N, Savage SA, Wong C, Backer K, et al
. Erythrocyte adenosine deaminase: diagnostic value for Diamond-Blackfan anaemia. Br J Haematol 2013;160:547-54.
Ip WF, Dupuis A, Ellis L, Beharry S, Morrison J, Stormon MO, et al
. Serum pancreatic enzymes define the pancreatic phenotype in patients with Shwachman-Diamond syndrome. J Pediatr 2002;141:259-65.
Vlachos A, Klein GW, Lipton JM. The Diamond Blackfan anemia registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia. J Pediatr Hematol Oncol 2001;23:377-82.
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;119:3815-9.
Willig TN, Niemeyer CM, Leblanc T, Tiemann C, Robert A, Budde J, et al
. Identification of new prognosis factors from the clinical and epidemiologic analysis of a registry of 229 Diamond-Blackfan anemia patients. DBA group of Société d’Hématologie et d’immunologie Pédiatrique (SHIP), Gesellshaft für Pädiatrische Onkologie und Hämatologie (GPOH), and the European society for pediatric hematology and immunology (ESPHI). Pediatr Res 1999;46:553-61.
Lipton JM, Atsidaftos E, Zyskind I, Vlachos A. Improving clinical care and elucidating the pathophysiology of Diamond Blackfan anemia: an update from the Diamond Blackfan anemia registry. Pediatr Blood Cancer 2006;46:558-64.
Narla A, Vlachos A, Nathan DG. Diamond Blackfan anemia treatment: past, present, and future. Semin Hematol 2011;48:117-23.
Lee H, Lyssikatos C, Atsidaftos E, Muir E, Gazda H, Beggs AH, et al
. Remission in patients with Diamond Blackfan anemia (DBA) appears to be unrestricted by phenotype or genotype. ASH Ann Meet Abst 2008;112:3092.
Alter BP. Inherited bone marrow failure syndromes. In: Nathan DG, Orkin SH, Look AT, Ginsburg D, editors. Nathan and Oski's hematology of infancy and childhood. Philadelphia, PA: WB Saunders; 2003. p. 280-365.
Yaris N, Erduran E, Cobanoglu U. Hodgkin lymphoma in a child with Diamond Blackfan anemia. J Pediatr Hematol Oncol 2006;28:234-6.
Gasser C. [Aplastic anemia (chronic erythroblastophthisis) and cortisone]. Schweiz Med Wochenschr 1951;81:1241-2.
Sjögren SE, Flygare J. Progress towards mechanism-based treatment for Diamond-Blackfan anemia. Sci World J 2012;2012:184362.
Ozsoylu S. Oral megadose methylprednisolone for Diamond-Blackfan anemia. Blood 1994;84:3245-7.
Buchanan GR; International Diamond-Blackfan Anemia Study Group. Oral megadose methylprednisolone therapy for refractory Diamond-Blackfan anemia. International Diamond-Blackfan anemia study group. J Pediatr Hematol Oncol 2001;23:353-6.
Sumimoto S, Kawai M, Kasajima Y, Hamamoto T. Intravenous gamma-globulin therapy in Diamond-Blackfan anemia. Acta Paediatr Jpn 1992;34:179-80.
Bejaoui M, Fitouri Z, Sfar MT, Lakhoua R. Failure of immunosuppressive therapy and high-dose intravenous immunoglobulins in four transfusion-dependent, steroid-unresponsive Blackfan-Diamond anemia patients. Haematologica 1993;78:38-9.
Fiorillo A, Poggi V, Migliorati R, Parasole R, Selleri C, Rotoli B. Unresponsiveness to erythropoietin therapy in a case of Blackfan Diamond anemia. Am J Hematol 1991;37:65.
Halperin DS, Estrov Z, Freedman MH. Diamond-Blackfan anemia: promotion of marrow erythropoiesis in vitro
by recombinant interleukin-3. Blood 1989;73:1168-74.
Dunbar CE, Smith DA, Kimball J, Garrison L, Nienhuis AW, Young NS. Treatment of Diamond-Blackfan anaemia with haematopoietic growth factors, granulocyte-macrophage colony stimulating factor and interleukin 3: sustained remissions following Il-3. Br J Haematol 1991;79:316-21.
Gillio AP, Faulkner LB, Alter BP, Reilly L, Klafter R, Heller G, et al
. Treatment of Diamond-Blackfan anemia with recombinant human interleukin-3. Blood 1993;82: 744-51.
Olivieri NF, Feig SA, Valentino L, Berriman AM, Shore R, Freedman MH. Failure of recombinant human interleukin-3 therapy to induce erythropoiesis in patients with refractory Diamond-Blackfan anemia. Blood 1994;83:2444-50.
Gomez-Almaguer D, Gonzalez-Llano O. Danazol in the treatment of Diamond Blackfan anemia [abstract]. Blood 1992;80:382a.
Leonard EM, Raefsky E, Griffith P, Kimball J, Nienhuis AW, Young NS. Cyclosporine therapy of aplastic anaemia, congenital and acquired red cell aplasia. Br J Haematol 1989;72:278-84.
Alessandri AJ, Rogers PC, Wadsworth LD, Davis JH. Diamond-Blackfan anemia and cyclosporine therapy revisited. J Pediatr Hematol Oncol 2000;22:176-9.
Bobey NA, Carcao M, Dror Y, Freedman MH, Dahl N, Woodman RC. Sustained cyclosporine-induced erythropoietic response in identical male twins with Diamond-Blackfan anemia. J Pediatr Hematol Oncol 2003;25:914-8.
Abkowitz JL, Powell JS, Nakamura JM, Kadin ME, Adamson JW. Pure red cell aplasia: response to therapy with anti-thymocyte globulin. Am J Hematol 1986;23:363-71.
Abkowitz JL, Schaison G, Boulad F, Brown DL, Buchanan GR, Johnson CA, et al
. Response of Diamond-Blackfan anemia to metoclopramide: evidence for a role for prolactin in erythropoiesis. Blood 2002;100:2687-91.
Akiyama M, Yanagisawa T, Yuza Y, Yokoi K, Ariga M, Fujisawa K, et al
. Successful treatment of Diamond-Blackfan anemia with metoclopramide. Am J Hematol 2005;78:295-8.
Leblanc TM, Da Costa L, Marie I, Demolis P, Tchernia G. Metoclopramide treatment in DBA patients: no complete response in a French prospective study. Blood 2007;109:2266-7.
Pospisilova D, Cmejlova J, Hak J, Adam T, Cmejla R. Successful treatment of a Diamond-Blackfan anemia patient with amino acid leucine. Haematologica 2007;92:e66-7.
Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, et al
; ACMG Laboratory Quality Assurance Committee. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 2015;17:405-24.
Kalia SS, Adelman K, Bale SJ, Chung WK, Eng C, Evans JP, et al
. Recommendations for reporting of secondary findings in clinical exome and genome sequencing, 2016 update (ACMG SF v2.0): a policy statement of the American College of Medical Genetics and Genomics. Genet Med 2017;19:249-55.
Kendig KI, Baheti S, Bockol MA, Drucker TM Hart SN, Heldenbrand JR, et al
. Sentieon DNASeq Variant Calling Workflow Demonstrates Strong Computational Performance and Accuracy. Front. Genet. 2019;10:736.
Li H, Durbin R. Fast and accurate long-read alignment with Burrows–Wheeler transform. Bioinformatics 2010;26:589-95.
McLaren W, Pritchard B, Rios D, Chen Y, Flicek P, Cunningham F. Deriving the consequences of genomic variants with the Ensembl API and SNP effect predictor. Bioinformatics 2010;26:2069-70.
Da Costa L, Moniz H, Simansour M, Tchernia G, Mohandas N, Leblanc T. Diamond-Blackfan anemia, ribosome and erythropoiesis. Transfus Clin Biol 2010;17:112-9.
Clinton C, Gazda HT. Diamond-Blackfan anemia 2009 [updated 2019 Mar 7]. In: Adam MP, Ardinger HH, Pagon RA, Wallace ES, editors. Gene reviews [Internet]. Seattle, WA: University of Washington; 1993–2019. Available from: https://www.ncbi.nlm.nih.gov/books/NBK7047/. [Last accessed on 2019 Sep 29].
Steinberg-Shemer O, Keel S, Dgany O, Walsh T, Noy-Lotan S, Krasnov T, et al
. Diamond Blackfan anemia: a nonclassical patient with diagnosis assisted by genomic analysis. J Pediatr Hematol Oncol 2016;38:e260-2.
Pospisilova D, Cmejlova J, Ludikova B, Stary J, Cerna Z, Hak J, et al
. The Czech national Diamond-Blackfan anemia registry: clinical data and ribosomal protein mutations update. Blood Cells Mol Dis 2012;48:209-18.
Dianzani I, Garelli E, Ramenghi U. Diamond-Blackfan anemia: a congenital defect in erythropoiesis. Haematologica 1996;81:560-72.
Engidaye G, Melku M, Enawgaw B. Diamond Blackfan anemia: genetics, pathogenesis, diagnosis and treatment. EJIFCC 2019;30:67-81.
Konno Y, Toki T, Tandai S, Xu G, Wang R, Terui K, et al
. Mutations in the ribosomal protein genes in Japanese patients with Diamond-Blackfan anemia. Haematologica 2010;95:1293-9.
Gerrard G, Valgañón M, Foong HE, Kasperaviciute D, Iskander D, Game L, et al
. Target enrichment and high-throughput sequencing of 80 ribosomal protein genes to identify mutations associated with Diamond-Blackfan anaemia. Br J Haematol 2013;162:530-6.
Berdel D, Romahn A, Burmeister W. [Pluriglandular insufficiency due to transfusion haemosiderosis in Blackfan-Diamond anaemia (author’s transl)]. Klin Padiatr 1980;192:91-4.
Lanes R, Lunar L, Carrillo E, Villaroel O, Gunczler P, Palacios A. Acipimox, a nicotinic acid analog, stimulates growth hormone secretion in short healthy prepubertal children. J Pediatr Endocrinol Metab 2000;13:1115-20.
Khincha PP, Savage SA. Genomic characterization of the inherited bone marrow failure syndromes. Semin Hematol 2013;50:333-47.
[Figure 1], [Figure 2], [Figure 3]