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Diamond-Blackfan anemia 5(DBA5)

MedGen UID:
382705
Concept ID:
C2675859
Disease or Syndrome
Synonyms: DBA5; RPL35A-Related Diamond-Blackfan Anemia
 
Gene (location): RPL35A (3q29)
 
Monarch Initiative: MONDO:0012925
OMIM®: 612528

Disease characteristics

Excerpted from the GeneReview: Diamond-Blackfan Anemia
Diamond-Blackfan anemia (DBA) is characterized by a profound normochromic and usually macrocytic anemia with normal leukocytes and platelets, congenital malformations in up to 50%, and growth deficiency in 30% of affected individuals. The hematologic complications occur in 90% of affected individuals during the first year of life. The phenotypic spectrum ranges from a mild form (e.g., mild anemia or no anemia with only subtle erythroid abnormalities, physical malformations without anemia) to a severe form of fetal anemia resulting in nonimmune hydrops fetalis. DBA is associated with an increased risk for acute myelogenous leukemia (AML), myelodysplastic syndrome (MDS), and solid tumors including osteogenic sarcoma. [from GeneReviews]
Authors:
Colin Sieff   view full author information

Additional description

From OMIM
Diamond-Blackfan anemia (DBA) is an inherited red blood cell aplasia that usually presents in the first year of life. The main features are normochromic macrocytic anemia, reticulocytopenia, and nearly absent erythroid progenitors in the bone marrow. Patients show growth retardation, and approximately 30 to 50% have craniofacial, upper limb, heart, and urinary system congenital malformations. The majority of patients have increased mean corpuscular volume, elevated erythrocyte adenosine deaminase activity, and persistence of hemoglobin F. However, some DBA patients do not exhibit these findings, and even in the same family, symptoms can vary between affected family members (summary by Landowski et al., 2013). For a discussion of genetic heterogeneity of Diamond-Blackfan anemia, see DBA1 (105650).  http://www.omim.org/entry/612528

Clinical features

From HPO
Hypospadias
MedGen UID:
163083
Concept ID:
C0848558
Congenital Abnormality
Abnormal position of urethral meatus on the ventral penile shaft (underside) characterized by displacement of the urethral meatus from the tip of the glans penis to the ventral surface of the penis, scrotum, or perineum.
Ventricular septal defect
MedGen UID:
42366
Concept ID:
C0018818
Congenital Abnormality
A hole between the two bottom chambers (ventricles) of the heart. The defect is centered around the most superior aspect of the ventricular septum.
Short stature
MedGen UID:
87607
Concept ID:
C0349588
Finding
A height below that which is expected according to age and gender norms. Although there is no universally accepted definition of short stature, many refer to "short stature" as height more than 2 standard deviations below the mean for age and gender (or below the 3rd percentile for age and gender dependent norms).
Low-set ears
MedGen UID:
65980
Concept ID:
C0239234
Congenital Abnormality
Upper insertion of the ear to the scalp below an imaginary horizontal line drawn between the inner canthi of the eye and extending posteriorly to the ear.
Global developmental delay
MedGen UID:
107838
Concept ID:
C0557874
Finding
A delay in the achievement of motor or mental milestones in the domains of development of a child, including motor skills, speech and language, cognitive skills, and social and emotional skills. This term should only be used to describe children younger than five years of age.
Macrocytic anemia
MedGen UID:
1920
Concept ID:
C0002886
Disease or Syndrome
A type of anemia characterized by increased size of erythrocytes with increased mean corpuscular volume (MCV) and increased mean corpuscular hemoglobin (MCH).
Erythroid hypoplasia
MedGen UID:
488912
Concept ID:
C0542035
Disease or Syndrome
Decreased count of erythroid precursor cells, that is, erythroid lineage cells in the bone marrow.
Reticulocytopenia
MedGen UID:
167812
Concept ID:
C0858867
Finding
A reduced number of reticulocytes in the peripheral blood.
Leukopenia
MedGen UID:
6073
Concept ID:
C0023530
Disease or Syndrome
An abnormal decreased number of leukocytes in the blood.
Hypertelorism
MedGen UID:
9373
Concept ID:
C0020534
Finding
Although hypertelorism means an excessive distance between any paired organs (e.g., the nipples), the use of the word has come to be confined to ocular hypertelorism. Hypertelorism occurs as an isolated feature and is also a feature of many syndromes, e.g., Opitz G syndrome (see 300000), Greig cephalopolysyndactyly (175700), and Noonan syndrome (163950) (summary by Cohen et al., 1995).

Professional guidelines

PubMed

Rao PV, Lu X, Pattee P, Turner M, Nandgaonkar S, Paturi BT, Roberts CT Jr, Nagalla SR
J Assoc Physicians India 2005 Jun;53:521-6. PMID: 16121806

Curated

Vlachos A, Dahl N, Dianzani I, Lipton JM
Eur J Hum Genet 2011 May;19(5) Epub 2011 Jan 19 doi: 10.1038/ejhg.2010.247. PMID: 21248735Free PMC Article

Recent clinical studies

Etiology

Lim YJ, Arbiv OA, Kalbfleisch ME, Klaassen RJ, Fernandez C, Rayar M, Steele M, Lipton JH, Cuvelier G, Pastore YD, Silva M, Brossard J, Michon B, Abish S, Sinha R, Corriveau-Bourque C, Breakey VR, Tole S, Goodyear L, Sung L, Zlateska B, Cada M, Dror Y
Eur J Haematol 2022 Apr;108(4):278-287. Epub 2022 Jan 13 doi: 10.1111/ejh.13733. PMID: 34897809
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
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Berdoukas V, Bohane T, Tobias V, De Silva K, Fraser I, Aessopos A, Lindeman R
Hematol J 2005;5(7):572-8. doi: 10.1038/sj.thj.6200569. PMID: 15692602
Koch WC, Massey GV
Pediatr Rev 1990 Nov;12(5):142-8. doi: 10.1542/pir.12-5-142. PMID: 2284214

Diagnosis

Wlodarski MW, Vlachos A, Farrar JE, Da Costa LM, Kattamis A, Dianzani I, Belendez C, Unal S, Tamary H, Pasauliene R, Pospisilova D, de la Fuente J, Iskander D, Wolfe L, Liu JM, Shimamura A, Albrecht K, Lausen B, Bechensteen AG, Tedgard U, Puzik A, Quarello P, Ramenghi U, Bartels M, Hengartner H, Farah RA, Al Saleh M, Hamidieh AA, Yang W, Ito E, Kook H, Ovsyannikova G, Kager L, Gleizes PE, Dalle JH, Strahm B, Niemeyer CM, Lipton JM, Leblanc TM; international Diamond-Blackfan anaemia syndrome guideline panel
Lancet Haematol 2024 May;11(5):e368-e382. doi: 10.1016/S2352-3026(24)00063-2. PMID: 38697731
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
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Wainwright MS, Martin PL, Morse RP, Lacaze M, Provenzale JM, Coleman RE, Morgan MA, Hulette C, Kurtzberg J, Bushnell C, Epstein L, Lewis DV
Ann Neurol 2001 Nov;50(5):612-9. doi: 10.1002/ana.1251. PMID: 11706967
Herman JH, Shirey RS, Smith B, Kickler TS, Ness PM
Transfusion 1987 May-Jun;27(3):253-6. doi: 10.1046/j.1537-2995.1987.27387235633.x. PMID: 3296341

Therapy

Lipton JM
Br J Haematol 2024 May;204(5):1598-1599. Epub 2024 Mar 14 doi: 10.1111/bjh.19404. PMID: 38485153
Lim YJ, Arbiv OA, Kalbfleisch ME, Klaassen RJ, Fernandez C, Rayar M, Steele M, Lipton JH, Cuvelier G, Pastore YD, Silva M, Brossard J, Michon B, Abish S, Sinha R, Corriveau-Bourque C, Breakey VR, Tole S, Goodyear L, Sung L, Zlateska B, Cada M, Dror Y
Eur J Haematol 2022 Apr;108(4):278-287. Epub 2022 Jan 13 doi: 10.1111/ejh.13733. PMID: 34897809
Babushok DV, Bessler M
Best Pract Res Clin Haematol 2015 Mar;28(1):55-68. Epub 2014 Nov 12 doi: 10.1016/j.beha.2014.11.004. PMID: 25659730Free PMC Article
Ganapathi KA, Austin KM, Lee CS, Dias A, Malsch MM, Reed R, Shimamura A
Blood 2007 Sep 1;110(5):1458-65. Epub 2007 May 2 doi: 10.1182/blood-2007-02-075184. PMID: 17475909Free PMC Article
Berdoukas V, Bohane T, Tobias V, De Silva K, Fraser I, Aessopos A, Lindeman R
Hematol J 2005;5(7):572-8. doi: 10.1038/sj.thj.6200569. PMID: 15692602

Prognosis

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
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
Caines AE, Kpodonu J, Massad MG, Chaer R, Evans A, Lee JC, Geha AS
J Heart Lung Transplant 2005 Apr;24(4):486-8. doi: 10.1016/j.healun.2004.02.009. PMID: 15797753
Wainwright MS, Martin PL, Morse RP, Lacaze M, Provenzale JM, Coleman RE, Morgan MA, Hulette C, Kurtzberg J, Bushnell C, Epstein L, Lewis DV
Ann Neurol 2001 Nov;50(5):612-9. doi: 10.1002/ana.1251. PMID: 11706967
Ramenghi U, Garelli E, Valtolina S, Campagnoli MF, Timeus F, Crescenzio N, Mair M, Varotto S, D'Avanzo M, Nobili B, Massolo F, Mori PG, Locatelli F, Gustavsson P, Dahl N, Dianzani I
Br J Haematol 1999 Mar;104(4):841-8. doi: 10.1046/j.1365-2141.1999.01267.x. PMID: 10192448
Koch WC, Massey GV
Pediatr Rev 1990 Nov;12(5):142-8. doi: 10.1542/pir.12-5-142. PMID: 2284214

Clinical prediction guides

Wilkes MC, Siva K, Chen J, Varetti G, Youn MY, Chae H, Ek F, Olsson R, Lundbäck T, Dever DP, Nishimura T, Narla A, Glader B, Nakauchi H, Porteus MH, Repellin CE, Gazda HT, Lin S, Serrano M, Flygare J, Sakamoto KM
Nat Commun 2020 Jul 3;11(1):3344. doi: 10.1038/s41467-020-17100-z. PMID: 32620751Free PMC Article
Ito K, Hayashi T, Inaguma Y, Terazawa T, Ando M, Ando Y, Tsuge M, Kato A, Shimato A, Suzuki S, Kato S, Tomita A, Yamada S, Emi N
Biol Pharm Bull 2019 Oct 1;42(10):1651-1657. Epub 2019 Jul 25 doi: 10.1248/bpb.b19-00184. PMID: 31341143
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
Am J Hum Genet 2018 Dec 6;103(6):930-947. Epub 2018 Nov 29 doi: 10.1016/j.ajhg.2018.10.027. PMID: 30503522Free PMC Article
van Kuilenburg AB, Zoetekouw L, Meijer J, Kuijpers TW
Nucleosides Nucleotides Nucleic Acids 2010 Jun;29(4-6):461-5. doi: 10.1080/15257771003741406. PMID: 20544538
Dianzani I, Garelli E, Ramenghi U
Paediatr Drugs 2000 Sep-Oct;2(5):345-55. doi: 10.2165/00128072-200002050-00002. PMID: 11022796

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