title: Congenital dysgranulopoietic neutropenia in two siblings: clinical, ultrastructural, and in vitro bone marrow culture studies.
abstract: Two siblings with congenital neutropenia are reported. The first patient, female, died after Pseudomonas sepsis. The second patient male, suffered from recurrent pyogenic infections, with a more benign course. Bone Marrow (BM) and Peripheral Blood (PB) analysis in the second patient revealed a reduced number of granules and myelin bodies in the PB neutrophils, suggesting a developmental defect of primary and secondary granules. BM promyelocytes were almost normal, but the myelocytes and metamyelocytes showed defective granulogenesis. The BM in vitro granulocyte-macrophage-colony-forming cell (GM-CFC) growth and the PB white blood cells (WBC) granulocyte-macrophage-colony-stimulating factor (GM-CSF) production, which were analyzed in the second patient, showed normal numbers of GM-CFC, with differentiation mostly toward monocytes and a defect in the GM-CSF production capacity. The second patient's PB mononuclear cells or serum did not inhibit normal GM-CFC when added to control BM cells. We suggest that in this specific form of congenital neutropenia, which is probably an autosomal recessive disorder, the abnormal neutrophil granule production and the defective provision of GM-CSF by PB WBC are unique pathognomonic characteristics, possibly associated with the overt neutropenia.
authors.affiliation: Pediatric Dept B, Central Emek Hospital, Afula, Israel.
authors.forename: A
authors.initials: A
authors.lastname: Koren
authors.forename: P B
authors.initials: PB
authors.lastname: Sela
authors.forename: Y
authors.initials: Y
authors.lastname: Barak
authors.forename: J
authors.initials: J
authors.lastname: Jammalieh
authors.forename: E
authors.initials: E
authors.lastname: Katzuni
mesh_terms: D000380:Agranulocytosis / Q000151:congenital*; D001853:Bone Marrow / Q000648:ultrastructure; D003115:Colony-Stimulating Factors / Q000096:biosynthesis; D046508:Culture Techniques; D005260:Female; D016178:Granulocyte-Macrophage Colony-Stimulating Factor; D006098:Granulocytes / Q000473:pathology*; D006133:Growth Substances / Q000096:biosynthesis; D006412:Hematopoietic Stem Cells / Q000502:physiology; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008264:Macrophages / Q000502:physiology; D008297:Male; D009503:Neutropenia / Q000151:congenital*; D009504:Neutrophils / Q000648:ultrastructure
chemical_list: D003115:Colony-Stimulating Factors; D006133:Growth Substances; D016178:Granulocyte-Macrophage Colony-Stimulating Factor