Kostmann syndrome

First described in 1956, Kostmann syndrome, also called congenital neutropenia, is characterized as "is characterized by an arrest of the maturation of neutrophil precursors at the promyelocytic stage of differentiation and low levels of mature neutrophils in peripheral blood." It was generally lethal before treatment with granulocyte colony-stimulating factor was available, although some individuals were protected with antibiotics. ==Genetics and molecular biology == As mentioned, the disease was first described in a group with considerable intermarriage. It had been believed to be an autosomal recessive disorder, but two suggested genes, ELA-2, the neutrophil elastase gene, or G-CSFR, which defines the G-CSF receptor, are normal in the survivors with the disease. One patient had an ELA-2 defect but her parents did not, suggesting a spontaneous mutation.

Diagnosis

The disease is usually detected after an infant presents with a severe infection, with severe neutropenia and:

• Temperature instability in newborn period
• Fever
• Irritability
• Localized site(s) of infection

Differential diagnosis

To be considered are:

Agammaglobulinemia Severe combined immunodeficiency disease Autoimmune neutropenia Chronic benign neutropenia Shwachman-Diamond syndrome Glycogen-storage disease Type I Methylmalonic acidemia Pearson syndrome Cyclic neutropenia Chediak-Higashi syndrome Myelokathexis Treatment G-CSF, often in high dosage, is the core of treatment, although stem cell transplantation has an increasing role. References