title: Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes--a new syndrome?
abstract: A new megathrombocytopenic syndrome with giant platelets in peripheral blood and severe thrombocytopenia was diagnosed in a 4-month-old boy. His clinical course included repeated hemorrhagic incidents leading to death at age 37 months. Bone marrow ultrastructural analysis revealed numerous dystrophic megakaryocytes with giant membrane complexes. Although these features were similar to those described for megakaryocytes in mice lacking the gene for transcription factor p45-NF-E2, no abnormalities in the p45-NF-E2 gene could be documented. Platelet membrane analysis showed a reduction in glycoprotein (GP) Ib, but normal content of GPIIb and GPIIIa. Analysis of genes encoding for GPIb alpha and beta, GPV, and GPIX ruled out the possibility that the observed platelet abnormality is a variant of Bernard-Soulier syndrome. A moderate neutropenia was associated with a complete lack of expression of sialyl-Lewis-X on the surface of polymorphonuclear neutrophils. A common defect in posttranslational modification of glycoproteins could account for the diverse cellular abnormalities.
authors.affiliation: Service de Pédiatrie et Laboratoire d'Hématologie, d'Immunologie et de Cytogénétique, CHU Kremlin Bicêtre, Assistance Publique-Hôpitaux de Paris, Le Kremlin Bicetre, France.
authors.forename: T B
authors.initials: TB
authors.lastname: Willig
authors.forename: J
authors.initials: J
authors.lastname: Breton-Gorius
authors.forename: C
authors.initials: C
authors.lastname: Elbim
authors.forename: V
authors.initials: V
authors.lastname: Mignotte
authors.forename: C
authors.initials: C
authors.lastname: Kaplan
authors.forename: R
authors.initials: R
authors.lastname: Mollicone
authors.forename: C
authors.initials: C
authors.lastname: Pasquier
authors.forename: A
authors.initials: A
authors.lastname: Filipe
authors.forename: F
authors.initials: F
authors.lastname: Miélot
authors.forename: J P
authors.initials: JP
authors.lastname: Cartron
authors.forename: M A
authors.initials: MA
authors.lastname: Gougerot-Pocidalo
authors.forename: N
authors.initials: N
authors.lastname: Debili
authors.forename: J
authors.initials: J
authors.lastname: Guichard
authors.forename: J P
authors.initials: JP
authors.lastname: Dommergues
authors.forename: N
authors.initials: N
authors.lastname: Mohandas
authors.forename: G
authors.initials: G
authors.lastname: Tchernia
mesh_terms: D001792:Blood Platelets / Q000378:metabolism / Q000648:ultrastructure; D006801:Humans; D007223:Infant; D007958:Leukocyte Count; D008297:Male; D008533:Megakaryocytes / Q000648:ultrastructure*; D009503:Neutropenia / Q000175:diagnosis* / Q000473:pathology; D009504:Neutrophils / Q000378:metabolism; D009844:Oligosaccharides / Q000378:metabolism*; D010976:Platelet Count; D010980:Platelet Membrane Glycoproteins / Q000378:metabolism; D000080506:Sialyl Lewis X Antigen; D013577:Syndrome; D013921:Thrombocytopenia / Q000175:diagnosis* / Q000378:metabolism / Q000473:pathology
chemical_list: D009844:Oligosaccharides; D010980:Platelet Membrane Glycoproteins; D000080506:Sialyl Lewis X Antigen