Pediatric Diamond-Blackfan anemia in the Netherlands: An overview of clinical characteristics and underlying molecular defects

Birgit van Dooijeweert, C. Heleen van Ommen, Frans J. Smiers, Rienk Y. J. Tamminga, Maroeska W. te Loo, Albertine E. Donker, Marjolein Peters, Bernd Granzen, Hans J. J. P. Gille, Marc B. Bierings, Alyson W. MacInnes, Marije Bartels*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

11 Citations (Web of Science)

Abstract

Introduction: Diamond-Blackfan anemia (DBA) is characterized by hypoplastic anemia, congenital anomalies, and a predisposition for malignancies. Most of our understanding of this disorder stems from molecular studies combined with extensive data input from international patient registries. Objectives: To create an overview of the pediatric DBA population in the Netherlands. Methods: Forty-three patients diagnosed with DBA from all Dutch university pediatric hospitals were included in this study, and their clinical and genetic characteristics were collected from patient records. Results: Congenital malformations were present in 24 of 43 patients (55.8%). An underlying genetic defect was identified in 26 of 43 patients (60.5%), the majority of which were found in the RPS19 gene (12 of 43, 27.9%) with 1 patient carrying a mutation in a novel DBA candidate gene, RPL9. In 31 of 35 (88.6%) patients, an initial response to glucocorticoid treatment was observed. Six patients (14.0%) underwent hematopoietic stem cell transplantation, and eleven patients (11 of 43, 25.6%) became treatment-independent spontaneously. Conclusion: In agreement with previous reports, the Dutch pediatric DBA population is both clinically and genetically heterogeneous. National and international registries, together with more extensive genetic testing, are crucial to increase our understanding of genotype and phenotype correlations of this intriguing disorder.
Original languageEnglish
Pages (from-to)163-170
Number of pages8
JournalEuropean Journal of Haematology
Volume100
Issue number2
DOIs
Publication statusPublished - 1 Feb 2018

Keywords

  • bone marrow failure
  • Diamond-Blackfan anemia
  • genotype-phenotype correlation
  • patient registry
  • ribosomopathy
  • STEM-CELL TRANSPLANTATION
  • MARROW FAILURE SYNDROMES
  • RIBOSOMAL-PROTEIN L5
  • RPL11 GENES
  • IN-VITRO
  • MUTATIONS
  • REGISTRY
  • RIBOSOMOPATHIES
  • ERYTHROPOIESIS
  • IDENTIFICATION

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