Congenital neutropenia and primary immunodeficiency diseases.

Abstract

Neutropenia is a dangerous and potentially fatal condition that renders patients vulnerable to recurrent infections. Its severity is commensurate with the absolute count of neutrophil granulocytes in the circulation. In paediatric patients, neutropenia can have many different aetiologies. Primary causes make up but a small portion of the whole and are relatively unknown. In the past decades, a number of genes has been discovered that are responsible for congenital neutropenia. By perturbation of mitochondrial energy metabolism, vesicle trafficking or synthesis of functional proteins, these mutations cause a maturation arrest in myeloid precursor cells in the bone marrow. Apart from these isolated forms, congenital neutropenia is associated with a multiplicity of syndromic diseases that includes among others: oculocutaneous albinism, metabolic diseases and bone marrow failure syndromes. Congenital neutropenia is a primary immunodeficiency disease that is associated with recurrent bacterial infections, auto-inflammatory and auto-immune phenomena, haematological malignancy and neuro-psychiatric manifestations. The aim of this review is to give a comprehensive overview of the most recent literature concerning the clinical, aetiological and genetic features of congenital neutropenia and the syndromes in which it might be encountered.