Macrothrombocytopenia with abnormal demarcation membranes in megakaryocytes and neutropenia with a complete lack of sialyl-Lewis-X antigen in leukocytes - a new syndrome?

A new megathrombocytopenic syndrome with giant platelets in peripheral bloo d and severe thrombocytopenia was diagnosed in a 4-month-old boy. His clini cal course included repeated hemorrhagic incidents leading to death at age 37 months. Bone marrow ultrastructural analysis revealed numerous dystrophi c megakaryocytes with giant membrane complexes. Although these features wer e similar to those described for megakaryocytes in mice lacking the gene fo r transcription factor p45-NF-E2, no abnormalities in the p45-NF-E2 gene co uld be documented. Platelet membrane analysis showed a reduction in glycopr otein (GP) Ib, but normal content of GPIIb and GPIIIa. Analysis of genes en coding for GPIb alpha and beta, GPV, and GPIX ruled out the possibility tha t the observed platelet abnormality is a variant of Bernard-Soulier syndrom e. A moderate neutropenia was associated with a complete lack of expression of sialyl-Lewis-X on the surface of polymorphonuclear neutrophils. A commo n defect in posttranslational modification of glycoproteins could account f or the diverse cellular abnormalities. (C) 2001 by The American Society of Hematology.