that may begin as apparently benign abnormalities but commonly progress to a more serious disorder. A small but significant percentage of individuals with GATA2 deficiency's present with congenital neutropenia. This neutropenia is typically mild, often persists for years, and therefore is not a Kostmann syndrome disorder. Over time, however, the deficiency commonly progresses to include thrombocytopenia, increases susceptibility to infections due to, e.g. atypical mycobacteria or human papillomavirus, dysfunction of non-hematological organs, the myelodysplastic syndrome, and/or a leukemia, particularly acute myelogenous leukemia. Pathophysiology The various mutations are responsible for the untimely initiation of apoptosis in myelocytes, usually at the promyelocyte stage, leading to their premature destruction or maturation arrest in the bone marrow. The ineffective production of neutrophils leads to a decrease in the absolute neutrophil count and a subsequent increased susceptibility to infections. There may be, in addition, other underlying molecular/genetic changes producing DNA mutations and genome instability, which contribute to initiation and progression of this disease. Diagnosis An absolute neutrophil count (ANC) chronically less than 500/mm3, usually less than 200/mm3, is the main sign of Kostmann's. Other elements include the severity of neutropenia, the chronology (from birth; not emerging later), and other normal findings (hemoglobin, platelets, general body health). Isolated neutropenia in infants can occur in viral infections, autoimmune neutropenia of infancy, bone marrow suppression from a drug or toxin, hypersplenism, and passive placental transfer of maternal IgG. A bone marrow test can assist in diagnosis. The bone marrow usually shows early granulocyte precursors, but myelopoietic development stops ("arrests") at the promyelocyte and/or myelocyte stage, so that few maturing forms are seen. Neutrophil survival is normal. Treatment Regular administration of exogenous granulocyte colony-stimulating factor (filgrastim) clinically improves neutrophil counts and immune function and is the mainstay of therapy, although this may increase risk for myelofibrosis and acute myeloid leukemia in the long term. Over 90% of SCN responds to treatment with granulocyte colony-stimulating factor (filgrastim), which has significantly improved survival. See also Neutropenia Cyclic neutropenia GATA2 deficiency References Further reading External links Search for Neutropenia to see on-going projects at Orphanet Severe Congenital Neutropenia (SCN) of Inherited Bone Marrow Failure Syndromes (IBMFS) Syndromes affecting blood Congenital defects of phagocyte number, function, or both Autosomal recessive disorders Autosomal dominant disorders Enzyme defects Rare diseases