Bone marrow nonneoplastic
Alterations in cellularity
Diamond-Blackfan anemia

Author: Guang (Geoff) Yang, M.D., Ph.D. (see Authors page)

Revised: 22 March 2017, last major update March 2017

Copyright: (c) 2003-2017, PathologyOutlines.com, Inc.

PubMed Search: Bone marrow Diamond-Blackfan anemia [title]
Cite this page: Diamond-Blackfan anemia. PathologyOutlines.com website. http://pathologyoutlines.com/topic/bonemarrowdiamondblackfan.html. Accessed December 13th, 2017.
Definition / general
  • A member of the inherited bone marrow failure syndromes (BMFS); typically shows an onset in the first year of life (Br J Haematol 2016;172:782)
  • Main features include normochromic macrocytic anemia, reticulocytopenia and nearly absent erythroid progenitors in the bone marrow (OMIM: Diamond-Blackfan Anemia 1)
  • Predisposition to acute myelogenous leukemia, myelodysplastic syndrome and solid tumors
Terminology
Essential features
  • Also known as Blackfan-Diamond anemia, congenital hypoplastic anemia and inherited erythroblastopenia
  • A member of the inherited bone marrow failure syndromes (BMFS); typically shows an onset in the first year of life (Br J Haematol 2016;172:782)
  • Underlying defect hypothesized to be faulty ribosome biogenesis, resulting in proapoptotic erythropoiesis and erythroid failure (Hematol Oncol Clin North Am 2009;23:261)
  • Growth retardation and various congenital abnormalities commonly seen
  • Normochromic macrocytic anemia, reticulocytopenia, normocellular for age marrow and nearly absent erythroid progenitors in the bone marrow (OMIM: Diamond-Blackfan Anemia 1)
  • Predisposition to acute myelogenous leukemia, myelodysplastic syndrome and solid tumors
Epidemiology
  • Incidence 1:100,000 ~ 1:200,000 live births and remains consistent across ethnicities (GeneReviews: Diamond-Blackfan Anemia)
  • Males and females equally affected
  • ~90% diagnosed within first year of life and 35% diagnosed within first month
Pathophysiology
  • ~55% are sporadic cases; ~45% familial with disease inherited mostly in an autosomal dominant pattern
  • Incomplete penetrance (GeneReviews: Diamond-Blackfan Anemia)
  • Underlying defect hypothesized to be faulty ribosome biogenesis, resulting in proapoptotic erythropoiesis and erythroid failure (Hematol Oncol Clin North Am 2009;23:261)
  • Heterozygous mutations in ribosomal proteins (RPs) encoding genes, both small and large ribosomal subunit, have been identified in 60% (Br J Haematol 2016;172:782)
  • Mutations identified in 15 RP genes: RPS7, RPS10, RPS17, RPS19, RPS24, RPS26, RPS27, RPS29, RPL5, RPL11, RPL15, RPL26, RPL27, RPL31, RPL35A (Br J Haematol 2016;172:782)
Diagrams / tables

Images hosted on other servers:

Missing Image

Hypothetic model for abortive
ribosome assembly and p53
activation relevant to DBA

Clinical features
  • Pallor, weakness, failure to thrive (GeneReviews: Diamond-Blackfan Anemia)
  • Growth retardation and various congenital abnormalities seen in 30% - 50%, in particular craniofacial, upper limb, heart and genitourinary malformations
  • Higher risk for developing certain malignancies including acute myelogenous leukemia, myelodysplastic syndrome and solid tumors
Diagnosis
    According to 6th Annual Diamond-Blackfan anemia (DBA) International Consensus Conference (Br J Haematol 2008;142:859)
  • Classic Diamond-Blackfan anemia is diagnosed if all of the following diagnostic criteria are met:
    • Age < 1 year
    • Macrocytic anemia with no other significant cytopenias
    • Reticulocytopenia
    • Normal marrow cellularity with a paucity of erythroid precursors
  • A probable diagnosis is made based on the following major and minor supporting criteria, if all of the above diagnostic criteria cannot be met :
    • Major supporting criteria:
      • The presence of a gene mutation associated with DBA
      • Positive family history
    • Minor supporting criteria
      • Elevated eADA activity
      • Congenital anomalies associated with DBA
      • Elevated Hemoglobin F
      • No evidence of another inherited bone marrow failure syndrome
    • A probable diagnosis of Diamond-Blackfan anemia can be made in the following settings:
      • Three diagnostic criteria and a positive family history
      • Two diagnostic criteria and three minor criteria
      • A positive family history and three minor criteria
  • Nonclassical DBA is diagnosed when there is a DBA associated gene mutation but insufficient diagnostic criteria
Laboratory
  • Macrocytic anemia with no other significant cytopenias (GeneReviews: Diamond-Blackfan Anemia)
  • Increased red cell mean corpuscular volume (MCV)
  • Reticulocytopenia
  • Elevated erythrocyte adenosine deaminase activity (eADA) (observed in 80% - 85%)
  • Elevated hemoglobin F (HbF) concentration
Prognostic factors
    Associated with unfavorable prognosis (Pediatr Res 1999;46:553)
  • Young age at presentation
  • No family history
  • Premature birth
Case reports
Treatment
Microscopic (histologic) description
  • Bone marrow examination usually shows normocellular for age, complete loss of erythroid elements or only scattered isolated erythroblasts
  • Increased hematogones, especially in infants and young children
  • Granulocytic and megakaryocytic lineages are preserved; mild eosinophilia is often present
Microscopic (histologic) images

Images hosted on other servers:

Missing Image Missing Image

Pure red cell aplasia (PRA)
Figures 1 and 5

Peripheral smear description
Molecular / cytogenetics description
  • Most common genetic causes of Diamond-Blackfan anemia (GeneReviews: Diamond-Blackfan Anemia)

    Gene % of DBA Attributed to
    Pathogenic Variants in This Gene
    RPL5 ~6.6%
    RPL11 ~4.8%
    RPL35A ~3%
    RPS10 ~2.6%
    RPS17 ~1%
    RPS19 ~25%
    RPS24 ~2%
    RPS26 ~6.4%
Differential diagnosis