Congenital neutropenia in children
Authors:
O. Fábri 1,2; J. Horáková 2; Z. Laluhová Striežencová 1
Authors‘ workplace:
Hematologicko-transfuziologické pracovisko, Oddelenie laboratórnej medicíny, Národný ústav detských chorôb, Bratislava, Slovensko
1; Klinika detskej hematológie a onkologie, Národný ústav detských chorôb, Bratislava, Slovensko
2
Published in:
Čes-slov Pediat 2021; 76 (4): 202-210.
Category:
Overview
Congenital neutropenia includes a heterogeneous group of rare hematological diseases characterized by impaired maturation of neutrophilic granulocytes. Recurrent infections, severe chronic neutropenia and the presence of congenital anomalies must give rise to suspicion of a genetic basis for the disease. CN includes a number of genetic disorders (so far > 24 genes) with chronic neutropenia, sometimes involving other organs such as the pancreas, central nervous system, bones and heart. The most common pathogenic aberrations are autosomal dominant mutations in the ELANE gene encoding neutrophil elastase and autosomal recessive mutations in HAX1, the product of which activates the granulocyte colony stimulating factor (G-CSF) signaling pathway. The pathophysiological mechanisms of these conditions are the subject of extensive research and are not fully understood.
Patients with severe congenital neutropenia are prone to recurrent, often life-threatening infections that begin in the first months of life. Children with CN are at increased risk of developing myelodysplastic syndrome or myeloid malignancies due to acquired mutations in the CSF3R gene or other leukemia-associated genes (RUNX1). The diagnosis is based on clinical manifestations, neutrophil count, bone marrow examination, genetic and immunological examination.
G-CSF is used in treatment to keep the ANC above 1x109/L. Regular monitoring of haematological parameters (once every 3 months) and bone marrow exam is also recommended to monitor the course of treatment and to detect chromosomal abnormalities. In patients who do not respond to treatment or progress to malignant transformation the only curative treatment is hematopoietic stem cell transplantation.
Keywords:
Neutropenia – congenital neutropenia – cytopenia – myelodysplastic syndrome – hematopoietic stem cell transplantation – growth factor – G-CSF
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Labels
Neonatology Paediatrics General practitioner for children and adolescentsArticle was published in
Czech-Slovak Pediatrics
2021 Issue 4
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