KOSTMANN SYNDROME (KOSTMANN INFANTILE AGRANULOCYTOSIS, SCN3,)
This is a rare autosomal recessive disorder characterized by granulocytopenia and monocytosis in infancy. There is an increased risk of myelodysplastic syndrome and/or AML in the severe congenital neutropenia syndromes, such that in follow-up study (mean 6 years), malignant transformation occurred in 10 % (Freedman et al. 2000). Neutropenia may respond to treatment with recombinant human granulocyte colony-stimulating factor. Recurrent homozygous mutations in the gene encoding HAX1, a mitochondrial protein implicated in preventing apoptosis in myeloid cells, have been identified in children with Kostmann syndrome (Klein et al. 2007). Other autosomal recessive severe congenital neutropenias (SCN) are mainly caused by mutations in ELA2, encoding ELANE, the neutrophil elastase gene. This variety of SCN is sometimes referred to as SCN1.
Mutations in GFI1, WAS, CSF3R, or G6PC3 are also seen, but are much less common (Xia et al. 2009). More than a third of all cases of SCN remain unexplained.