Official reprint from UpToDate®
www.uptodate.com ©2017 UpToDate, Inc. and/or its affiliates. All Rights Reserved.

Inherited aplastic anemia in children and adolescents

Timothy S Olson, MD, PhD
Section Editor
Donald H Mahoney, Jr, MD
Deputy Editor
Jennifer S Tirnauer, MD


Aplastic anemia (AA) is a rare disorder characterized by pancytopenia and a hypocellular bone marrow [1-3]. AA can result from either inherited or acquired causes (table 1). The incidence is triphasic, with one peak in childhood at two to five years (due to inherited causes), and two peaks in adulthood, 20 to 25 years and the majority of patients presenting beyond 55 to 60 years of age (typically due to acquired causes) [1]. The associated neutropenia and thrombocytopenia can lead to potentially life-threatening infections and bleeding. Chronic red cell transfusion therapy for the associated anemia can lead iron overload, which, if not treated, can lead to significant morbidity and mortality.

The majority of children (75 percent) with inherited bone marrow failure have an identifiable etiology [4-6]. The four major inherited causes for AA in children are:

Fanconi anemia (FA)

Dyskeratosis congenita (DC)

Shwachman-Diamond syndrome (SDS)

To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:

Subscribers log in here

Literature review current through: Nov 2017. | This topic last updated: Apr 05, 2017.
The content on the UpToDate website is not intended nor recommended as a substitute for medical advice, diagnosis, or treatment. Always seek the advice of your own physician or other qualified health care professional regarding any medical questions or conditions. The use of this website is governed by the UpToDate Terms of Use ©2017 UpToDate, Inc.
  1. Alter BP. Inherited Bone Marrow Failure Syndromes. In: Nathan and Oski's Hematology of Infancy and Childhood, Nathan DG, Orkin SH, Ginsburg D, Look AT (Eds), W.B. Saunders, Philadelphia 2003. p.280.
  2. Young NS. Acquired aplastic anemia. Ann Intern Med 2002; 136:534.
  3. Brodsky RA, Jones RJ. Aplastic anaemia. Lancet 2005; 365:1647.
  4. Teo JT, Klaassen R, Fernandez CV, et al. Clinical and genetic analysis of unclassifiable inherited bone marrow failure syndromes. Pediatrics 2008; 122:e139.
  5. Khincha PP, Savage SA. Genomic characterization of the inherited bone marrow failure syndromes. Semin Hematol 2013; 50:333.
  6. Chirnomas SD, Kupfer GM. The inherited bone marrow failure syndromes. Pediatr Clin North Am 2013; 60:1291.
  7. Guinan EC, Lee YS, Lopez KD, et al. Effects of interleukin-3 and granulocyte-macrophage colony-stimulating factor on thrombopoiesis in congenital amegakaryocytic thrombocytopenia. Blood 1993; 81:1691.
  8. Ballmaier M, Germeshausen M. Advances in the understanding of congenital amegakaryocytic thrombocytopenia. Br J Haematol 2009; 146:3.
  9. Ihara K, Ishii E, Eguchi M, et al. Identification of mutations in the c-mpl gene in congenital amegakaryocytic thrombocytopenia. Proc Natl Acad Sci U S A 1999; 96:3132.
  10. van den Oudenrijn S, Bruin M, Folman CC, et al. Mutations in the thrombopoietin receptor, Mpl, in children with congenital amegakaryocytic thrombocytopenia. Br J Haematol 2000; 110:441.
  11. Ballmaier M, Germeshausen M, Schulze H, et al. c-mpl mutations are the cause of congenital amegakaryocytic thrombocytopenia. Blood 2001; 97:139.
  12. Tijssen MR, di Summa F, van den Oudenrijn S, et al. Functional analysis of single amino-acid mutations in the thrombopoietin-receptor Mpl underlying congenital amegakaryocytic thrombocytopenia. Br J Haematol 2008; 141:808.
  13. Cremer M, Schulze H, Linthorst G, et al. Serum levels of thrombopoietin, IL-11, and IL-6 in pediatric thrombocytopenias. Ann Hematol 1999; 78:401.
  14. Berthet F, Caduff R, Schaad UB, et al. A syndrome of primary combined immunodeficiency with microcephaly, cerebellar hypoplasia, growth failure and progressive pancytopenia. Eur J Pediatr 1994; 153:333.
  15. King S, Germeshausen M, Strauss G, et al. Congenital amegakaryocytic thrombocytopenia: a retrospective clinical analysis of 20 patients. Br J Haematol 2005; 131:636.
  16. Young NS, Alter BP. Aplastic Anemia: Acquired and Inherited, WB Saunders, Philadelphia 1994. p.13.
  17. Maserati E, Panarello C, Morerio C, et al. Clonal chromosome anomalies and propensity to myeloid malignancies in congenital amegakaryocytic thrombocytopenia (OMIM 604498). Haematologica 2008; 93:1271.
  18. Walne AJ, Dokal A, Plagnol V, et al. Exome sequencing identifies MPL as a causative gene in familial aplastic anemia. Haematologica 2012; 97:524.
  19. Muraoka K, Ishii E, Tsuji K, et al. Defective response to thrombopoietin and impaired expression of c-mpl mRNA of bone marrow cells in congenital amegakaryocytic thrombocytopenia. Br J Haematol 1997; 96:287.
  20. MacMillan ML, Davies SM, Wagner JE, Ramsay NK. Engraftment of unrelated donor stem cells in children with familial amegakaryocytic thrombocytopenia. Bone Marrow Transplant 1998; 21:735.
  21. Lackner A, Basu O, Bierings M, et al. Haematopoietic stem cell transplantation for amegakaryocytic thrombocytopenia. Br J Haematol 2000; 109:773.
  22. Mehta P, Locatelli F, Stary J, Smith FO. Bone marrow transplantation for inherited bone marrow failure syndromes. Pediatr Clin North Am 2010; 57:147.
  23. Mahadeo KM, Tewari P, Parikh SH, et al. Durable engraftment and correction of hematological abnormalities in children with congenital amegakaryocytic thrombocytopenia following myeloablative umbilical cord blood transplantation. Pediatr Transplant 2015; 19:753.
  24. Woods G, Bajwa RP, Rose MJ. Reduced intensity transplantation for congenital amegakaryocytic thrombocytopenia: report of a case and review of the literature. Pediatr Transplant 2014; 18:E31.