Diamond-Blackfan anemia natural history, complications and prognosis

Overview

DBA typically present with common symptoms of anemia, including pale skin, sleepiness, irritability, tachycardia. Common complications of DBA include physical abnormalities, Cancer predisposition, eye problems such as cataracts, glaucoma, or strabismus, kidney abnormalities, hypospadias, and secondary complications due to standard therapies( Corticosteroids treatment, Red cell transfusion, Bone marrow transplantation). Prognosis is relatively good, overall actuarial survival is 75% at age 40 years

Diamond-Blackfan anemia natural history, complications and prognosis

Natural 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.^[1]^[2]The severity of Diamond-Blackfan anemia may vary, even within the same family.

Complications

Common complications of Diamond-Blackfan anemia include:
Physical abnormalities
higher-than-average chance of developing myelodysplastic syndrome (MDS), acute myeloid leukemia (AML), bone cancer (osteosarcoma), colon cancer^[3]
Eye problems such as cataracts, glaucoma, or strabismus
kidney abnormalities
hypospadias
Secondary complications due to standard therapies( Corticosteroids treatment, Red cell transfusion, Bone marrow transplantation):
- Oragans involvement due to 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

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. ^[4]

Ultimately, 40% of case subjects remain dependent upon corticosteroids which increase the risk of heart disease, osteoporosis, and severe infections. ^[5]
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.^[6]

References

↑ 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.
↑ 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.
↑ Gadhiya K, Budh DP. PMID 31424886. Missing or empty |title= (help)
↑ 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.
↑ 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.

[pmid23349008-1] 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.

[pmid29599205-2] 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.

[pmid20012593-3] 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.

[pmid31424886-4] Gadhiya K, Budh DP. PMID 31424886. Missing or empty |title= (help)

[pmid20960466-5] 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.

[pmid23016900-6] 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.

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