title: Recurrent infections and immunological dysfunction in congenital disorder of glycosylation Ia (CDG Ia).
abstract: Congenital disorder of glycosylation Ia is the most common defect of glycosylation and is due to mutations in phosphomannomutase 2. This leads to aberrant N-linked oligosaccharides. The phenotype of CDG Ia reflects the essential nature of glycosylation and patients typically present with multiple organs affected, with hypotonia, developmental delay, inverted nipples and abnormal fat pads. Later features include retinitis pigmentosa, stroke, cerebellar atrophy and malabsorption. Approximately 20% of patients die in the first year of life and infection is the most common cause of death. Immunological function has not previously been investigated in these patients and the critical role of oligosaccharides on adhesion molecules suggested that haematopoietic cell migration and communication could be disrupted by mutations in phosphomannomutase 2. We characterized the clinical features, performed standard immunological evaluations, and performed specific analyses of neutrophil adhesion molecules on two patients to address this question. Patient neutrophils had diminished chemotaxis but expressed comparable levels of adhesion molecules and rolled on artificial endothelium equivalently to control neutrophils. The most significant feature of the patients' immunological function was poor vaccine responses. These two affected patients were begun on intravenous immunoglobulin with some improvement in their infections.
authors.affiliation: Gettysburg Pediatrics, Gettysburg, Pennsylvania, USA.
authors.forename: C
authors.initials: C
authors.lastname: Blank
authors.forename: L A
authors.initials: LA
authors.lastname: Smith
authors.forename: D A
authors.initials: DA
authors.lastname: Hammer
authors.forename: M
authors.initials: M
authors.lastname: Fehrenbach
authors.forename: H M
authors.initials: HM
authors.lastname: Delisser
authors.forename: E
authors.initials: E
authors.lastname: Perez
authors.forename: K E
authors.initials: KE
authors.lastname: Sullivan
mesh_terms: D001402:B-Lymphocytes / Q000276:immunology; D002239:Carbohydrate Metabolism, Inborn Errors / Q000150:complications* / Q000276:immunology* / Q000628:therapy; D015815:Cell Adhesion Molecules / Q000032:analysis; D002634:Chemotaxis, Leukocyte; D002675:Child, Preschool; D006031:Glycosylation; D006801:Humans; D007136:Immunoglobulins / Q000097:blood; D016756:Immunoglobulins, Intravenous / Q000627:therapeutic use; D007223:Infant; D007239:Infections / Q000209:etiology*; D008297:Male; D009504:Neutrophils / Q000276:immunology; D012008:Recurrence; D013601:T-Lymphocytes / Q000276:immunology; D014612:Vaccines / Q000276:immunology
chemical_list: D015815:Cell Adhesion Molecules; D007136:Immunoglobulins; D016756:Immunoglobulins, Intravenous; D014612:Vaccines