Severe congenital Kostmann neutropenia

Severe congenital neutropenia or Kostmann syndrome or infantile agranulocytosis (SCN3, OMIM: 610738 ) is an AR-inherited disease characterized by marked neutropenia and severe bacterial infections. The genetic basis is a mutation of the HAX1 gene (1q21.3). There are also other forms of severe congenital neutropenia, for example autosomal dominantly inherited (mutations of the GFI1 gene - 1p22 or the ELA2 gene - 19p13.3).

Pathogenesis

 * Disruption of the signaling cascade through the G-CSF pathway causes the absence of all stages of maturation from promyelocytes,
 * Phagocytosis is impaired.

Clinical picture

 * Already in the first days of life – fever, skin and umbilical cord infections, stomatitis,
 * Infections tend to generalize,
 * The most common causative agents: Staphylococcus aureus, E. coli, Pseudomonas aeruginosa.

Diagnostics

 * Blood count + differential: profound neutropenia,
 * Bone marrow: almost complete absence of promyelocytes and myelocytes with a normal number of myeloid lineage.

Treatment

 * Recombinant G-CSF (long-term side effects: osteoporosis, bone fibrosis, splenomegaly),
 * Event. bone marrow transplantation.

Related Articles

 * Primary immunodeficiency
 * Neutropenia in children