G-CSF Kostmann's syndrome is an inherited disorder of the bone marrow. It is also known as severe congenital neutropenia. It is inherited in an autosomal recessive manner. Congenital neutropenia is usually very severe and neutrophils are often completely absent in the blood of these patients at the time of diagnosis. These patients usually show arrest of maturation of neutrophils at the promyelocyte stage. - This means that their neutrophils rarely. fully mature into the cells that are capable of fighting infections. - As a result these patients usually suffer from severe infections ? - Omphalitis (infection of the navel) - Pneumonia - Skin abscesses - Otitis media during their first few years of life. Pathogenesis Kostmann's syndrome or severe congenital neutropenia is believed to he caused by defect in a gene on chromosome (in p35-p34.3) that codes for granulocyte colony stimulating factor (GCSF). This disease is believed to be caused due to defect in receptor in granulocyte colony stimulator factor. - This receptor is located on granulocytes or neutrophils. The purpose of this receptor is the binding of the granulocyte to the cytokine (GCSF) in order to give signal to the cell to mature, to multiply, and enhance .function. GCSF is a natural cytokine produced by the human body. - Patients with congenital neutropenia also produce GCSF hut because of the defect in GCSF receptor the response of their neutrophils to the normal amounts of GCSF in the blood is reduced. - These patients will respond to higher dose of GCSF (This is the basis of tit of disease). In some patients the GCSF receptor develops changes that could also indicate progression towards leukemia. Treatment Patients with congenital neutropenia respond to administration of GCSF. - As soon as congenital neutropenia is diagnosed, patients should sta treatment with GCSF. - This treatment usually stabilizes the neutrophil count of the patient. - The response of these patients to GCSF treatment is different. There is a big variation in the dose of GCSF that different people receive. - A small group of patient does not respond to even very high doses of GCSF. In patients who do not respond to GCSF doses of 100 mcg/kg within foueen days, a search for bone marrow donor should be staed immediately and bone marrow transplantation should be performed as soon as matching donor is identified.