Birgit van Dooijeweert1, C Heleen van Ommen2, Frans J Smiers3, Rienk Y J Tamminga4, Maroeska W Te Loo5, Albertine E Donker6, Marjolein Peters7, Bernd Granzen8, Hans J J P Gille9, Marc B Bierings1, Alyson W MacInnes10, Marije Bartels1. 1. Department of Pediatric Hematology, University Medical Center Utrecht, Utrecht, The Netherlands. 2. Department of Pediatric Hematology, Erasmus Medical Center, Rotterdam, The Netherlands. 3. Department of Pediatric Hematology, Leiden University Medical Center, Leiden, The Netherlands. 4. Department of Pediatric Hematology, University Medical Center Groningen, Groningen, The Netherlands. 5. Department of Pediatric Hematology, Radboud University Medical Center, Nijmegen, The Netherlands. 6. Department of Pediatrics, Maxima Medical Center, Veldhoven, The Netherlands. 7. Department of Pediatric Hematology, Academic Medical Center Amsterdam, Amsterdam, The Netherlands. 8. Department of Pediatric Hematology, Maastricht University Medical Center, Maastricht, The Netherlands. 9. Department of Clinical Genetics, VU University Medical Center, Amsterdam, The Netherlands. 10. Laboratory Genetic Metabolic Diseases, Academic Medical Center Amsterdam, Amsterdam, The Netherlands.
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.
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.
Authors: Brigitte Strahm; Felicia Loewecke; Charlotte M Niemeyer; Michael Albert; Marc Ansari; Peter Bader; Yves Bertrand; Birgit Burkhardt; Lydie M Da Costa; Alina Ferster; Alexandra Fischer; Tayfun Güngör; Bernd Gruhn; Ina Hainmann; Friedrich Kapp; Peter Lang; Ingo Müller; Ansgar Schulz; Amina Szvetnik; Marcin Wlodarski; Peter Noellke; Thierry Leblanc; Jean-Hugues Dalle Journal: Blood Adv Date: 2020-04-28
Authors: Anna Aspesi; Marta Betti; Marika Sculco; Chiara Actis; Cristina Olgasi; Marcin W Wlodarski; Adrianna Vlachos; Jeffrey M Lipton; Ugo Ramenghi; Claudio Santoro; Antonia Follenzi; Steven R Ellis; Irma Dianzani Journal: Hum Mutat Date: 2018-05-28 Impact factor: 4.878
Authors: Birgit Van Dooijeweert; Melissa H Broeks; Nanda M Verhoeven-Duif; Eduard J Van Beers; Edward E S Nieuwenhuis; Wouter W Van Solinge; Marije Bartels; Judith J Jans; Richard Van Wijk Journal: Haematologica Date: 2021-10-01 Impact factor: 9.941