title: Congenital disorders of the function of polymorphonuclear neutrophils.
abstract: This review has concentrated on clinical syndromes for which a congenital basis of polymorphonuclear neutrophil dysfunction has been identified. The first clinical syndrome found to be associated with dysfunctional polymorphs was chronic granulomatous disease of childhood. Identification of a cellular defect in oxidative metabolism and microbicidal activity of polymorphonuclear neutrophils from patients with CGD stimulated intense investigation of the function of phagocytes in several clinical entities characterized by increased susceptibility to infection. Other diseases with a probable congenital basis for polymorph dysfunction include Chediak-Higashi syndrome, myeloperoxidase deficiency, severe glucose-6-phosphate dehydrogenase deficiency, and Down's syndrome. Functional defects have also been identified in neutrophils with morphologic abnormalities, such as the Pelger-Huet anomaly and the May-Hegglin anomaly, and in neutrophils without alkaline phosphatase or with a disorder of the glutathione system. The evidence for a relation between these cellular disorders and susceptibility to infection is tentative. Patients with congenital disorders of polymorphonuclear neutrophil microbicidal function frequently suffer prolonged infections in spite of appropriate antimicrobial therapy, and severe lesions recur with discouraging frequency. These lesions are usually soft tissue or bone abscesses, and the etiologic agents are typically staphylococci, gram-negative enteric species, or fungi. The infectious disease problems of patients with phagocytic cell disorders are usually quite distinct from the problems of patients without immunoglobulins or with complement deficiency. Patients with agammaglobulinemia, for example, suffer recurrent septicemia or meningitis due to Streptococcus pneumonia or H. influenzae. Septicemia, especially with the pyogenic bacterial species, is unusual in patients with polymorphoinuclear dysfunction. A major contribution of the currently intense investigation of cells from patients with congenital disorders of phagocyte function has been the greatly increased understanding of the molecular events necessary for the normal function of these cells. The role of the oxidative metabolic burst during phagocytosis has been clearly identified as essential to the microbicidal function of polymorphs and monocytes, and the glutathione system has been identified as essential to the regulation of these oxidative reactions. It is anticipated that these studies may lead to practical methods for "stimulating the phagocytes" in patients with increased susceptibility to infection.
mesh_terms: D000469:Alkaline Phosphatase / Q000172:deficiency; D002609:Chediak-Higashi Syndrome / Q000235:genetics; D004314:Down Syndrome / Q000097:blood; D005260:Female; D005980:Glutathione Reductase / Q000172:deficiency; D006105:Granulomatous Disease, Chronic / Q000151:congenital / Q000235:genetics / Q000382:microbiology; D006402:Hematologic Diseases / Q000097:blood / Q000151:congenital*; D006801:Humans; D008297:Male; D008361:Mannosidases / Q000172:deficiency; D009504:Neutrophils / Q000503:physiopathology*; D010381:Pelger-Huet Anomaly / Q000097:blood; D009195:Peroxidase / Q000172:deficiency
chemical_list: D009195:Peroxidase; D005980:Glutathione Reductase; D000469:Alkaline Phosphatase; D008361:Mannosidases