Which are the causes of Kostmann Syndrome?

Kostmann Syndrome, also known as severe congenital neutropenia (SCN), is a rare genetic disorder characterized by a severe decrease in the number of neutrophils, a type of white blood cell that plays a crucial role in the immune system's defense against bacterial infections. This condition is primarily caused by mutations in the ELANE gene, which provides instructions for producing an enzyme called neutrophil elastase.

Neutrophil elastase is essential for the maturation and function of neutrophils. Mutations in the ELANE gene lead to a dysfunctional or absent neutrophil elastase, resulting in impaired neutrophil development and survival. As a consequence, individuals with Kostmann Syndrome have a significantly reduced number of neutrophils in their bloodstream, making them highly susceptible to recurrent and severe bacterial infections.

Genetic mutations in the ELANE gene are the primary cause of Kostmann Syndrome. These mutations can be inherited in an autosomal recessive manner, meaning that an affected individual must inherit two copies of the mutated gene, one from each parent, to develop the condition. If both parents carry a single copy of the mutated gene, they are considered carriers and have a 25% chance of having an affected child with each pregnancy.

While the majority of Kostmann Syndrome cases are caused by mutations in the ELANE gene, there have been rare instances where mutations in other genes, such as HAX1 and G6PC3, have been associated with a similar severe congenital neutropenia phenotype.

Environmental factors do not play a significant role in the development of Kostmann Syndrome. It is primarily a genetic disorder caused by mutations in specific genes involved in neutrophil production and function.

Early diagnosis of Kostmann Syndrome is crucial to initiate appropriate treatment and prevent life-threatening infections. Genetic testing can confirm the presence of mutations in the ELANE gene or other associated genes, helping to establish a definitive diagnosis. Treatment typically involves the administration of granulocyte colony-stimulating factor (G-CSF), a medication that stimulates the production of neutrophils. Regular monitoring and preventive measures, such as prophylactic antibiotics, are also essential to manage the condition and minimize the risk of infections.