title: Kostmann syndrome and severe congenital neutropenia.
abstract: Congenital neutropenia (CN) includes hematologic disorders characterized by severe neutropenia with an absolute neutrophil count (ANC) below 0.5 x 10(9)/L associated with severe systemic bacterial infections from early infancy. One subtype of CN, Kostmann syndrome, was originally described as an autosomal-recessive disorder, characterized by early-stage maturation arrest of myelopoiesis. Autosomal-dominant and sporadic cases have also been reported. Recent studies on the genetic bases of CN have detected different inherited or spontaneous point mutations in the neutrophil elastase gene. Development of additional genetic defects during the course of disease, such as granulocyte colony-stimulating factor (G-CSF)-receptor gene mutations and cytogenetic aberrations, indicates an underlying genetic instability. Data on more than 300 patients with CN collected by the Severe Chronic Neutropenia International Registry (SCNIR) since 1994 demonstrate that, independent of the CN subtype, more than 90% of patients respond to recombinant human (rHu)G-CSF with ANCs that can be maintained at approximately 1.0 x 10(9)/L. Adverse events include mild splenomegaly, moderate thrombocytopenia, osteoporosis, and malignant transformation into myelodysplasia (MDS)/leukemia. If and how rHuG-CSF treatment impacts on these adverse events remains unclear since there are no historical controls for comparison. Hematopoietic stem cell transplantation (HSCT) is still the only available treatment for patients refractory to rHuG-CSF treatment.
authors.affiliation: Department for Pediatric Hematology/Oncology Kinderklinik, Medizinische Hochschule Hannover, Hannover, Germany.
authors.forename: Cornelia
authors.initials: C
authors.lastname: Zeidler
authors.forename: Karl
authors.initials: K
authors.lastname: Welte
mesh_terms: D020732:Cytogenetic Analysis; D016179:Granulocyte Colony-Stimulating Factor / Q000627:therapeutic use; D006801:Humans; D009503:Neutropenia / Q000150:complications / Q000151:congenital* / Q000473:pathology / Q000628:therapy; D016188:Receptors, Granulocyte Colony-Stimulating Factor / Q000235:genetics; D033581:Stem Cell Transplantation; D013577:Syndrome
chemical_list: D016188:Receptors, Granulocyte Colony-Stimulating Factor; D016179:Granulocyte Colony-Stimulating Factor