Definition of Disease, Kostmann

Disease, Kostmann: A condition with a lack of neutrophils (a type of white blood cell that is important in fighting infection). Children with this disease suffer frequent infections from bacteria which in the past led to death in three-quarters of cases before 3 years of age. This disease is also known as severe congenital neutropenia (SCN).

Children with severe congenital neutropenia have no special problems with viral or fungal infections. They do, however, have an increased risk of developing acute myelogenous leukemia or myelodysplasia, a bone marrow disorder. Aside from agranulocytosis, the bone marrow and blood show a number of other abnormalities (including a failure of neutrophil precursors to mature beyond the promyelocyte stage, absolute increase in monocytes (monocytosis), and an increase in the numbers of eosinophilic white blood cells (eosinophilia) and in the numbers of platelets (thrombocytosis). The gamma globulin type of protein level in blood is low.

The inheritance of the disease is autosomal recessive. Both seemingly-normal parents carry a severe congenital neutropenia gene while each of their children, boys and girls alike, has a 1 in 4 (25%) risk of receiving both severe congenital neutropenia genes and having the disease: severe congenital neutropenia (SCN).

Severe congenital neutropenia was first clearly described by Kostmann in 1956. It is now known to be caused by a defect in a gene on chromosome 1 (in 1p35-p34.3) that codes for what is called the granulocyte colony-stimulating factor receptor (GCSFR).

Treatment with recombinant human granulocyte colony-stimulating factor (GCSF) elevates the granulocyte counts, helps resolve preexisting infections, diminishes the number of new infections and results in significant improvements in survival and quality of life. Some patients have developed leukemia or myelodysplastic syndrome following treatment with GCSF.

Congenital neutropenia is due to diverse causes. Not all patients with congenital neutropenia have mutations in the GCSFR gene.

Alternative names for Kostmann's disease (or syndrome) include not only severe congenital neutropenia (SCN) but also infantile genetic agranulocytosis and genetic infantile agranulocytosis.