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Congenital disorder of fucosylation type 2c (LADII) presenting with short stature and developmental delay with minimal adhesion defect

2014; Oxford University Press; Volume: 23; Issue: 11 Linguagem: Inglês

10.1093/hmg/ddu001

1460-2083

Andrew Dauber, Altan Ercan, Jack Y. Lee, Philip E. James, Pieter P. Jacobs, David J. Ashline, Sophie R. Wang, Timothy C. Miller, Joel N. Hirschhorn, Peter A. Nigrović, Robert Sackstein,

Immunodeficiency and Autoimmune Disorders

Leukocyte adhesion deficiency type II is a hereditary disorder of neutrophil migration caused by mutations in the guanosine diphosphate-fucose transporter gene (SLC35C1). In these patients, inability to generate key fucosylated molecules including sialyl Lewis X leads to leukocytosis and recurrent infections, in addition to short stature and developmental delay. We report two brothers with short stature and developmental delay who are compound heterozygotes for novel mutations in SLC35C1 resulting in partial in vivo defects in fucosylation. Specifically, plasma glycoproteins including immunoglobulin G demonstrated marked changes in glycoform distribution. While neutrophil rolling on endothelial selectins was partially impeded, residual adhesion proved sufficient to avoid leukocytosis or recurrent infection. These findings demonstrate a surprising degree of immune redundancy in the face of substantial alterations in adhesion molecule expression, and show that short stature and developmental delay may be the sole presenting signs in this disorder.