Disorder of hematopoiesis with an absolute neutrophil count persistently below 500/µL, with maturation arrest of neutrophils the promyelocyte level.
Prior to granulocyte colony stimulating factor use approximately half of affected children dies during the first year of life from sepsis.
Mortality rate during second to fourth years was 6-7% per year before stimulating factor therapy.
patients at risk for the development of acute myelogenous leukemia or myelodysplastic syndrome.
Almost all patients respond to G-CSF therapy with reduction in infections and hospitalizations.
Kostmann form of severe congenital neutropenia is very rare and is caused by mutations in the HAX1 gene, which encodes HAX1, a mitochondrial protein that inhibits apoptosis.
Autonomic dominant and sporadic forms of severe congenital neutropenia caused by mutations in the ELA2 gene, which encodes the serine protease neutrophil elastase.
ELA2 mutations account for 50-60% of cases.
Rare cases associated with mutations of the genes encoding the Wiskott-Aldrich syndrome protein (WAS), colony stimulating factor 3 receptor (CSF3R), and growth factor independent 1 protein (GF11)
Main clinical feature is onset of severe bacterial infections early in life, few mature neutrophils, and associated with an increased risk of leukemia.
Consists of heterogeneous disorders that respond to recombinant human granulocyte colony stimulating factor, but patients remain at risk for infections and development of clonal disorders such as myelodysplastic syndrome and acute myelogenous leukemia.