Diamond-Blackfan anemia
| Diamond-Blackfan anemia | |
| ICD-10 | D61.0 |
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| ICD-9 | 284.01 |
| OMIM | 105650 |
| DiseasesDB | 29062 |
| MeSH | D029503 |
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Diamond-Blackfan anemia Microchapters |
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Diagnosis |
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Treatment |
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Case Studies |
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Diamond-Blackfan anemia On the Web |
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American Roentgen Ray Society Images of Diamond-Blackfan anemia |
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Risk calculators and risk factors for Diamond-Blackfan anemia |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1] Associate Editor(s)-in-Chief: Roghayeh Marandi[2]
Synonyms and keywords: Erythrogenesis imperfecta; congenital pure red cell aplasia, hereditary pure red cell aplasia, familial pure red cell aplasia
Overview
Historical Perspective
Pathophysiology
Mutations in ribosomal protein genes have been confirmed to be the direct cause of faulty erythropoiesis and anemia.[1]. DBA has revealed itself as a "Ribosomapthy".
| Ribosomal protein gene mutations---> Ribosomal protein Insufficiency ---> Imbalance of Ribosomal Assembly Intermediates ---> Free Ribosomal proteins bind to inhibitors of P53 and Stabilize P53 expression ---> P53 Activation ---> Cell Cycle Arrest |
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Researchers found Ribosomal protein gene mutations reduce the actual numbers of ribosomes in blood precursor cells. Without enough ribosomes, the precursors can’t produce enough GATA1, which is essential for precursor cells to differentiate into red blood cells, so mature red cells never form. 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.[2] Finally, this phenomenon results in the DBA phenotype of anemia, deprived growth, and results in congenital abnormalities. Mutated RP genes in DBA encode ribosomal proteins which are involved in either the small (RPS) or large (RPL) subunits of these proteins and the scarcity of these proteins can result the development of the disease.[3] Other blood cells — like platelets, T cells, and B cells — are not affected and can still develop since they’re not dependent on GATA1.[4][5][6][7][8]
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 may account for the DBA phenotype. [9]
Causes
- in about 80-85% of cases Diamond-Blackfan anemia, a block in erythropoiesis occurs due to the ribosomal protein gene mutation. [10][1]
- 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. [9]
- Ribosomal protein mutations are sprodaic(55%) or hereditary.
- Sporadic mutation occurs in genes encoding several different ribosomal proteins.
- Approximately 40-45 % DBA cases are inherited with an autosomal dominant inheritance.[11][12] and they have a family history of the disease with varying phenotypes.[9], although some of cases (GATA1-related DBA and TSR2-related DBA) are inherited in an X-linked manner.[13].Also, autosomal recessive inheritance, with a lesser frequency has been reported.[14]Variable expressivity is seen in all RP gene mutations. Possible mechanisms underlying variable expressivity include an influence of modifier genes and environmental factors. [15]
- About 25% of patients have mutations in the ribosome protein S19 (RPS19) gene on chromosome 19 at cytogenetic position 19q13.2. RPS19 has an important role in 18S rRNA maturation in yeast and in human cells.
- Other mutated genes have 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, that result in small or large ribosomal subunit synthesis deficiencies in human cells[9] [16]
- Mutation of "Non-RP" genes such as TSR2 and GATA1, and EPO also were found.[9][17][18][8][19]TSR2 plays a role in ribosome biogenesis since it is involved in the pre-rRNA processing and binds to RPS26. GATA1 which is the major erythroid transcription factor as being essential for precursor cells to differentiate into red blood cells and plays a critical role in regulating normal erythroid differentiation by activating of other erythroid genes.
Differentiating Diamond-Blackfan anemia from other Diseases
- Aplastic anemia
- Fanconi anemia is a bone marrow failure syndrome, present with pancytopenia, and physical abnormalities usually present within the first decade of life.
- Transient Erythroblastopenia of Childhood is anacquired anemia usually (over 80%) presents at one year of age, while DBA usually (90%) presents before one year of age.[20]
- Shwachman-Diamond syndrome (SDS) is a clinical syndrome characterized by exocrine pancreatic dysfunction with malabsorption, single or multi-lineage cytopenia, growth failure, bone abnormality, and susceptibility to myelodysplastic syndrome, and AML[21][22]
- Pearson syndrome is an inherited mDNA mutation characterized by sideroblastic anemia of childhood, exocrine pancreatic failure, liver failure, renal tubular defects, and pancytopenia. Death generally occurs in infancy due to liver failure.
- Dyskeratosis congenita (DC) is an inheretied disorder with the classic triad of lacy reticular pigmentation of the upper chest and/or neck, dysplastic nails, and oral leukoplakia. These patients have an increased risk of MDS, BMF, or AML. [21]
- Cartilage-hair hypoplasia (CHH)It is an autosomal recessive inherited disorder characterized by anemia, macrocytosis, defective T cell-mediated immune response, short tubular bone, and fine sparse blond hair.
- Congenital amegakaryocytic thrombocytopenia (CAMT) usually presents at birth or in infancy with severe thrombocytopenia, petechiae, and/or intracranial or intestinal mucosal bleeding. In childhood, these patients may develop pancytopenia, MDS, or leukemia.
- Infections: Parvovirus B19, HIV, Viral hepatitis
- Drugs and toxins (eg. antileptic drugs, azathioprine)[13]
- Immune-mediated disorders( eg Thymoma, Myasthenia Gravis, SLE)
Epidemiology and Demographics
- Incidence
Incidence of Classical Diamond-Blackfan anemia (DBA) is 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.[23]
- Prevalence of DBA
It is approximately 5000 cases worldwide.
- Age
DBA is usually first diagnosed in infancy. The average age of presenting with anemia is two months and the average age of diagnosis with DBA is 3-4 months.
- Race
There is no racial predilection to DBA.
- Gender
DBA affects men and women equally.[24]
Risk Factors
- Positive family history of DBA
- Have a known genetic cause
- The cause cannot be detected, in some cases
Natural History, Complications and Prognosis
Natural history
The severity of Diamond-Blackfan anemia may vary, even within the same family.
- Classic DBA:
- Approximately half of DBA cases have 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
- All diagnostic criteria are met.
- Non-classic DBA:
- presents with mild or absent anemia with only subtle indications of erythroid abnormalities such as macrocytosis, elevated ADA, and/or elevated HbF concentration
- Have mild anemia beginning later in childhood or in adulthood, while others have some of the physical features but no bone marrow problems.
- Minimal or no evidence of congenital anomalies or short stature[13]
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[25]
- Eye problems such as cataracts, glaucoma, or strabismus
- kidney abnormalities
- hypospadias
- Secondary complications due to standard therapies( Corticosteroids treatment, Red cell transfusion, Bone marroe transplantation):
- Transfusion iron overload
- Cirrhosis or fibrosis of the liver
- Cardiac arrythmias
- Diabetes
- Reproductive organ failure
- Growth stunting
- Endocrine failure affecting the thyroid and adrenal
- Side effects of corticosteroids
- Osteoporosis
- Weight gain
- Cushingoid appearance
- Hypertension
- Diabetes mellitus
- Growth retardation
- Pathologic bone fractures
- Gastric ulcers
- Cataracts
- Glaucoma
- Increased susceptibility to infection
- Stem cell transplantation
- Graft vs. Host Disease (GVHD)
- Rejection
- Transfusion iron overload
Prognosis
- Prognosis is relatively good,Overall actuarial survival is 75% at age 40 years, but complications related to treatment may alter the quality of life of the affected individuals. Severe complications as a result of treatment or the development of cancer may reduce life expectancy. [20]
- Hematopoietic stem cell transplant (HSCT) is the sole curative option, but carries significant morbidity and is generally restricted to those with a matched related donor.[26]
- Ultimately, 40% of case subjects remain dependent upon corticosteroids which increase the risk of heart disease, osteoporosis, and severe infections. [15]
- Another 40% become dependent upon red cell transfusions which require regular chelation to prevent iron overload and increases the risk of alloimmunization and transfusion reactions, and can cause severe co-morbidities.[27]
Diagnosis
History and Symptoms | Physical Examination | Laboratory Findings | Electrocardiogram | Chest X Ray | CT | MRI | Echocardiography or Ultrasound | Other Imaging Findings | Other Diagnostic Studies
Diagnosis
- Diagnosing DBA is usually hard due to its partial phenotypes and the wide inconsistency of clinical expressions. the International Clinical Consensus Conference stated diagnostic and supporting criteria for the diagnosis of DBA.[23]
- Diagnostic criteria
- Normochromic, often macrocytic anemia developing in the first year of life
- Profound reticulocytopenia
- Normocellular bone marrow with selective deficiency of erythroid precursors
- Normal or slightly reduced leukocyte count
- Normal or slightly increased platelet count
- Major supporting criteria
- Gene mutation described in ‘‘classical’’ DBA
- Positive family history
- Minor supporting criteria
- Elevated erythrocyte adenosine deaminase activity
- Congenital anomalies described in ‘‘classical’’ DBA
- Elevated HbF
- No evidence of another inherited bone marrow failure syndrome
| Classical DBA
All diagnostic criteria are met
3 Diagnostic criteria + positive family history OR 2 Diagnostic criteria + 3 minor criteria OR 3 Minor criteria + positive family history
DBA associated gene mutation without sufficient diagnostic criteria |
History and symptoms
History
- DBA typically presents in infancy, most commonly with pallor and lethargy, median age at presentation is 8 weeks. Hydrops fetalis in some cases have been seen.[28][29]
Symptoms
- Symptoms of anemia include pallor, irritability, failure to thrive, sleepiness, poor appetite, and weakness[9]
- Growth retardation (in about 30% )
- Congenital malformations, in particular craniofacial, upper-limb, heart, and genitourinary malformations:(~30%-50%):
Physical exam
Appearance of the Patient
- Pallor: primary hematologic feature is characterized by anemia (low red blood cell counts),usually develops during the neonatal period.
- Congenital malformations( observed in approximately 50% of affected individuals):
- Head and face (50%)
- Microcephaly
- hypertelorism
- Epicanthus
- Ptosis
- Microtia
- low-set ears
- Broad, depressed nasal bridge
- Cleft lip/palate
- High arched palate
- Micrognathia
- low anterior hairline
- Eye
- Congenital glaucoma
- Congenital cataract
- strabismus
- Neck
- Webbing, short neck,
- Klippel-Feil anomaly
- Sprengel deformity
- Upper limb and hand including thumb (38%)
- Absent radial artery
- Flat thenar eminence
- Triphalangeal, duplex, bifid, hypoplastic, or absent thumb
- Genitourinary (19%).
- Absent kidney
- horseshoe kidney
- hypospadias
- Heart (15%)
- Ventricular septal defect
- Atrial septal defect
- coarctation of the aorta
- Growth
- Low birth weight (in 25% of affected infants)
- Growth retardation9in 30%.Growth retardation can be influenced by other factors including steroid treatment
- Head and face (50%)
Following Initial Diagnosis, patients should be evaluated by:
- a hematologist
- a clinical geneticist for congenital malformations and to obtain a detailed family history
- an ophthalmologist for glaucoma and cataract for individuals on steroid therapy
- an Orthopedic evaluation for individuals with clinical findings suggestive of Klippel-Feil anomaly or Sprengel deformity
- Orthopedic for individuals with upper-limb and/or thumb anomalies
- Ultrasound examination of the kidney and urinary tract
- a nephrologist and a urologist, as appropriate
- a cardiologist including echocardiography
- Developmental assessment
Laboratory findings
Blood tests:
- Increased red-cell mean corpuscular volume (MCV)
- Reticulocytopenia
- Elevated erythrocyte adenosine deaminase activity(eADA)
- DBA is associated with an increased ADA activity 30– 33%. ADA is a critical enzyme of the purine salvage pathway, which enables the deamination of adenosine in inosine and 2'-deoxyadenosine deamination in deoxyinosine. It is also increased in some leukemias, lymphomas, and immune system disorders.[30] [31]
- Elevated hemoglobin F (HbF) concentration
Genetic tests
1. A sequence analysis of RPS19 is performed first.
2. If no pathogenic variant in RPS19 is found, perform sequence analysis of the remaining pathologic variants which are known to cause DBA or other gene mutations.[13]
Bone marrow aspirate
- Normal marrow cellularity
- Erythroid hypoplasia
- Marked reduction in normoblasts
- Persistence of pronormoblasts on occasion
- Normal myeloid precursors and megakaryocytes[13]
Other tests
- Additional blood tests or genetic tests such as exome sequencing, genome sequencing, and mitochondrial sequencing may be ordered to rule out other types of anemia or other disorders.
- Diagnosis of related-therapies complications:
- Monitoring Transfusional Iron Overload with serum ferritin and Iron level. Here is a list of recommended labs to monitor and prevent the devastating effects of iron overload in the thyroid, heart, and the effects of diabetes:
- Total T3
- Total T4
- TSH
- T3 uptake (instead of free T4)
- IGF-1(monitors acute fluctuations in insulin action and determines inadequate insulin treatment or poor control of dietary intake)
- NT-proBNP (aids in the diagnosis of left ventricular dysfunction in heart failure)
- Antithyroid Abs (Antithyroglobulin and AntiThyroperoxidase)
- Fructosamine (useful in situations where the A1C cannot be reliably measured – as with transfused persons)
- Vitamin D
- Monitoring Transfusional Iron Overload with serum ferritin and Iron level. Here is a list of recommended labs to monitor and prevent the devastating effects of iron overload in the thyroid, heart, and the effects of diabetes:
Treatment
Medical Therapy | Surgery | Cost-Effectiveness of Therapy | Future or Investigational Therapies
- Red cell transfusions
- Transfusions are usually the mainstay of treatment for the first year of life for the anemia of DBA. Also, Red blood transfusions are used for those patients who do not respond to corticosteroid treatment
- Corticosteroid therapy
- after the first year patients are started on a course of treatment with corticosteroids and it remains the mainstay of treatment after the original report of their efficacy. In a large study of 225 patients, 82% initially responded to this therapy, although many side effects were noted.[32] Treatment with corticosteroids can improve the anemia in 80% of patients, but individuals often become intolerant to long-term corticosteroid therapy and turn to regular red blood cell transfusions, which is the only available standard therapy for the anemia. [10]
- Chronic glucocorticoid therapy predisposes patients to iatrogenic Cushing syndrome and adrenal insufficiency.
- Chronic blood transfusions place patients at risk for the iron overload of the liver, heart, and endocrine organs. Growth failure, osteopenia, diabetes mellitus, and failure of the thyroid, parathyroids, adrenals, gonads, and pituitary gland, may be related to therapy.[33]
- Bone marrow transplantation (BMT)
- It is the only curative treatment for the anemia of DBA. This option may be considered when patients become transfusion-dependent because frequent transfusions can lead to iron overloading and organ damage. This can be done using an unaffected sibling or an unrelated donor.
- Periods of remission may occur, during which transfusions and steroid treatments are not required. Remission defined as an adequate Hemoglobin level without any treatment, lasting 6 months, independent of prior therapy. 72% of patients experience remission during the first decade of life. Some of them have more than one remission in their life. Relapses usually occur after a viral illness.
- Some patients who have such mild signs and symptoms do not require treatment.[3]
- Cancer treatment
Prevention of secondary complications
- Iron chelation
- usually started after ten to 12 transfusions (170-200 mL/kg of packed red blood cells), when serum ferritin concentration reaches 1,000-1,500 µg/L, or when the hepatic iron concentration reaches 6-7 mg/g of dry weight liver tissue
- Deferasirox is recommended in individuals age two years or older.
- Desferrioxamine
- usually started after ten to 12 transfusions (170-200 mL/kg of packed red blood cells), when serum ferritin concentration reaches 1,000-1,500 µg/L, or when the hepatic iron concentration reaches 6-7 mg/g of dry weight liver tissue
- Corticosteroids side effects:
- One of the critical side effects of corticosteroids is growth retardation. If growth is severely impaired, corticosteroids should be stopped.[13]
Further or investigational therapies
- Investigations of several other agents showed these drugs appear to be largely ineffective and there is currently no evidence that any of these has a major role in the management of DBA [23]
- Intravenous immunoglobulin
- High dose erythropoietin
- Interleukin-3
- Androgens
- Metoclopramide
- Leucine and lenalidomide
- Researchers still wants to know why steroids often work in DBA, find more mutations, and address some questions about Diamond-Blackfan anemia.[10]
Case Studies
External Links
- ↑ 1.0 1.1 Vlachos A, Dahl N, Dianzani I, Lipton JM (October 2013). "Clinical utility gene card for Diamond-Blackfan anemia--update 2013". Eur. J. Hum. Genet. 21 (10). doi:10.1038/ejhg.2013.34. PMC 3778360. PMID 23463023.
- ↑ McGowan KA, Li JZ, Park CY, Beaudry V, Tabor HK, Sabnis AJ, Zhang W, Fuchs H, de Angelis MH, Myers RM, Attardi LD, Barsh GS (August 2008). "Ribosomal mutations cause p53-mediated dark skin and pleiotropic effects". Nat. Genet. 40 (8): 963–70. doi:10.1038/ng.188. PMC 3979291. PMID 18641651.
- ↑ Lipton JM, Ellis SR (April 2009). "Diamond-Blackfan anemia: diagnosis, treatment, and molecular pathogenesis". Hematol. Oncol. Clin. North Am. 23 (2): 261–82. doi:10.1016/j.hoc.2009.01.004. PMC 2886591. PMID 19327583.
- ↑ O'Brien KA, Farrar JE, Vlachos A, Anderson SM, Tsujiura CA, Lichtenberg J, Blanc L, Atsidaftos E, Elkahloun A, An X, Ellis SR, Lipton JM, Bodine DM (June 2017). "Molecular convergence in ex vivo models of Diamond-Blackfan anemia". Blood. 129 (23): 3111–3120. doi:10.1182/blood-2017-01-760462. PMC 5465839. PMID 28377399.
- ↑ Ulirsch JC, Lareau C, Ludwig LS, Mohandas N, Nathan DG, Sankaran VG (August 2017). "Confounding in ex vivo models of Diamond-Blackfan anemia". Blood. 130 (9): 1165–1168. doi:10.1182/blood-2017-05-783191. PMC 5580274. PMID 28615220.
- ↑ Boultwood J, Pellagatti A (July 2014). "Reduced translation of GATA1 in Diamond-Blackfan anemia". Nat. Med. 20 (7): 703–4. doi:10.1038/nm.3630. PMID 24999938.
- ↑ Ludwig LS, Gazda HT, Eng JC, Eichhorn SW, Thiru P, Ghazvinian R, George TI, Gotlib JR, Beggs AH, Sieff CA, Lodish HF, Lander ES, Sankaran VG (July 2014). "Altered translation of GATA1 in Diamond-Blackfan anemia". Nat. Med. 20 (7): 748–53. doi:10.1038/nm.3557. PMC 4087046. PMID 24952648.
- ↑ 8.0 8.1 Khajuria RK, Munschauer M, Ulirsch JC, Fiorini C, Ludwig LS, McFarland SK, Abdulhay NJ, Specht H, Keshishian H, Mani DR, Jovanovic M, Ellis SR, Fulco CP, Engreitz JM, Schütz S, Lian J, Gripp KW, Weinberg OK, Pinkus GS, Gehrke L, Regev A, Lander ES, Gazda HT, Lee WY, Panse VG, Carr SA, Sankaran VG (March 2018). "Ribosome Levels Selectively Regulate Translation and Lineage Commitment in Human Hematopoiesis". Cell. 173 (1): 90–103.e19. doi:10.1016/j.cell.2018.02.036. PMC 5866246. PMID 29551269.
- ↑ 9.0 9.1 9.2 9.3 9.4 9.5 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.
- ↑ 10.0 10.1 10.2 Ulirsch JC, Verboon JM, Kazerounian S, Guo MH, Yuan D, Ludwig LS, Handsaker RE, Abdulhay NJ, Fiorini C, Genovese G, Lim ET, Cheng A, Cummings BB, Chao KR, Beggs AH, Genetti CA, Sieff CA, Newburger PE, Niewiadomska E, Matysiak M, Vlachos A, Lipton JM, Atsidaftos E, Glader B, Narla A, Gleizes PE, O'Donohue MF, Montel-Lehry N, Amor DJ, McCarroll SA, O'Donnell-Luria AH, Gupta N, Gabriel SB, MacArthur DG, Lander ES, Lek M, Da Costa L, Nathan DG, Korostelev AA, Do R, Sankaran VG, Gazda HT (December 2018). "The Genetic Landscape of Diamond-Blackfan Anemia". Am. J. Hum. Genet. 103 (6): 930–947. doi:10.1016/j.ajhg.2018.10.027. PMC 6288280. PMID 30503522.
- ↑ Ball S (2011). "Diamond Blackfan anemia". Hematology Am Soc Hematol Educ Program. 2011: 487–91. doi:10.1182/asheducation-2011.1.487. PMID 22160079.
- ↑ Garçon L, Ge J, Manjunath SH, Mills JA, Apicella M, Parikh S, Sullivan LM, Podsakoff GM, Gadue P, French DL, Mason PJ, Bessler M, Weiss MJ (August 2013). "Ribosomal and hematopoietic defects in induced pluripotent stem cells derived from Diamond Blackfan anemia patients". Blood. 122 (6): 912–21. doi:10.1182/blood-2013-01-478321. PMC 3739037. PMID 23744582.
- ↑ 13.0 13.1 13.2 13.3 13.4 13.5 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
|title=(help) - ↑ Engidaye G, Melku M, Enawgaw B (March 2019). "Diamond Blackfan Anemia: Genetics, Pathogenesis, Diagnosis and Treatment". EJIFCC. 30 (1): 67–81. PMC 6416817. PMID 30881276.
- ↑ 15.0 15.1 Boria I, Garelli E, Gazda HT, Aspesi A, Quarello P, Pavesi E, Ferrante D, Meerpohl JJ, Kartal M, Da Costa L, Proust A, Leblanc T, Simansour M, Dahl N, Fröjmark AS, Pospisilova D, Cmejla R, Beggs AH, Sheen MR, Landowski M, Buros CM, Clinton CM, Dobson LJ, Vlachos A, Atsidaftos E, Lipton JM, Ellis SR, Ramenghi U, Dianzani I (December 2010). "The ribosomal basis of Diamond-Blackfan Anemia: mutation and database update". Hum. Mutat. 31 (12): 1269–79. doi:10.1002/humu.21383. PMC 4485435. PMID 20960466.
- ↑ Choesmel V, Fribourg S, Aguissa-Touré AH, Pinaud N, Legrand P, Gazda HT, Gleizes PE (May 2008). "Mutation of ribosomal protein RPS24 in Diamond-Blackfan anemia results in a ribosome biogenesis disorder". Hum. Mol. Genet. 17 (9): 1253–63. doi:10.1093/hmg/ddn015. PMID 18230666.
- ↑ Sankaran VG, Ghazvinian R, Do R, Thiru P, Vergilio JA, Beggs AH, Sieff CA, Orkin SH, Nathan DG, Lander ES, Gazda HT (July 2012). "Exome sequencing identifies GATA1 mutations resulting in Diamond-Blackfan anemia". J. Clin. Invest. 122 (7): 2439–43. doi:10.1172/JCI63597. PMC 3386831. PMID 22706301.
- ↑ Klar J, Khalfallah A, Arzoo PS, Gazda HT, Dahl N (September 2014). "Recurrent GATA1 mutations in Diamond-Blackfan anaemia". Br. J. Haematol. 166 (6): 949–51. doi:10.1111/bjh.12919. PMID 24766296.
- ↑ Kim AR, Ulirsch JC, Wilmes S, Unal E, Moraga I, Karakukcu M, Yuan D, Kazerounian S, Abdulhay NJ, King DS, Gupta N, Gabriel SB, Lander ES, Patiroglu T, Ozcan A, Ozdemir MA, Garcia KC, Piehler J, Gazda HT, Klein DE, Sankaran VG (March 2017). "Functional Selectivity in Cytokine Signaling Revealed Through a Pathogenic EPO Mutation". Cell. 168 (6): 1053–1064.e15. doi:10.1016/j.cell.2017.02.026. PMC 5376096. PMID 28283061.
- ↑ 20.0 20.1 Gadhiya K, Budh DP. PMID 31424886. Missing or empty
|title=(help) - ↑ 21.0 21.1 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.
- ↑ Boocock GR, Morrison JA, Popovic M, Richards N, Ellis L, Durie PR, Rommens JM (January 2003). "Mutations in SBDS are associated with Shwachman-Diamond syndrome". Nat. Genet. 33 (1): 97–101. doi:10.1038/ng1062. PMID 12496757.
- ↑ 23.0 23.1 23.2 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.
- ↑ Willig TN, Niemeyer CM, Leblanc T, Tiemann C, Robert A, Budde J, Lambiliotte A, Kohne E, Souillet G, Eber S, Stephan JL, Girot R, Bordigoni P, Cornu G, Blanche S, Guillard JM, Mohandas N, Tchernia G (November 1999). "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. 46 (5): 553–61. doi:10.1203/00006450-199911000-00011. PMID 10541318.
- ↑ Luft F (January 2010). "The rise of a ribosomopathy and increased cancer risk". J. Mol. Med. 88 (1): 1–3. doi:10.1007/s00109-009-0570-0. PMID 20012593.
- ↑ Roy V, Pérez WS, Eapen M, Marsh JC, Pasquini M, Pasquini R, Mustafa MM, Bredeson CN (August 2005). "Bone marrow transplantation for diamond-blackfan anemia". Biol. Blood Marrow Transplant. 11 (8): 600–8. doi:10.1016/j.bbmt.2005.05.005. PMID 16041310.
- ↑ Horos R, von Lindern M (December 2012). "Molecular mechanisms of pathology and treatment in Diamond Blackfan Anaemia". Br. J. Haematol. 159 (5): 514–27. doi:10.1111/bjh.12058. PMID 23016900.
- ↑ 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.
- ↑ Glader BE, Backer K (February 1988). "Elevated red cell adenosine deaminase activity: a marker of disordered erythropoiesis in Diamond-Blackfan anaemia and other haematologic diseases". Br. J. Haematol. 68 (2): 165–8. doi:10.1111/j.1365-2141.1988.tb06184.x. PMID 3348976.
- ↑ Willig TN, Pérignon JL, Gustavsson P, Gane P, Draptchinskaya N, Testard H, Girot R, Debré M, Stéphan JL, Chenel C, Cartron JP, Dahl N, Tchernia G (December 1998). "High adenosine deaminase level among healthy probands of Diamond Blackfan anemia (DBA) cosegregates with the DBA gene region on chromosome 19q13. The DBA Working Group of Société d'Immunologie Pédiatrique (SHIP)". Blood. 92 (11): 4422–7. PMID 9834249.
- ↑ Vlachos A, Klein GW, Lipton JM (2001). "The Diamond Blackfan Anemia Registry: tool for investigating the epidemiology and biology of Diamond-Blackfan anemia". J. Pediatr. Hematol. Oncol. 23 (6): 377–82. PMID 11563775.
- ↑ Lahoti A, Harris YT, Speiser PW, Atsidaftos E, Lipton JM, Vlachos A (February 2016). "Endocrine Dysfunction in Diamond-Blackfan Anemia (DBA): A Report from the DBA Registry (DBAR)". Pediatr Blood Cancer. 63 (2): 306–12. doi:10.1002/pbc.25780. PMC 4829065. PMID 26496000.