title: Congenital disorder of fucosylation type 2c (LADII) presenting with short stature and developmental delay with minimal adhesion defect.
abstract: 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.
authors.affiliation: Division of Endocrinology.
authors.forename: Andrew
authors.initials: A
authors.lastname: Dauber
authors.forename: Altan
authors.initials: A
authors.lastname: Ercan
authors.forename: Jack
authors.initials: J
authors.lastname: Lee
authors.forename: Philip
authors.initials: P
authors.lastname: James
authors.forename: Pieter P
authors.initials: PP
authors.lastname: Jacobs
authors.forename: David J
authors.initials: DJ
authors.lastname: Ashline
authors.forename: Sophie R
authors.initials: SR
authors.lastname: Wang
authors.forename: Timothy
authors.initials: T
authors.lastname: Miller
authors.forename: Joel N
authors.initials: JN
authors.lastname: Hirschhorn
authors.forename: Peter A
authors.initials: PA
authors.lastname: Nigrovic
authors.forename: Robert
authors.initials: R
authors.lastname: Sackstein
mesh_terms: D049628:Body Size; D002448:Cell Adhesion; D018981:Congenital Disorders of Glycosylation / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D002658:Developmental Disabilities / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D006801:Humans; D007964:Leukocytosis / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009004:Monosaccharide Transport Proteins / Q000235:genetics* / Q000378:metabolism; D009504:Neutrophils / Q000166:cytology* / Q000378:metabolism; D055815:Young Adult
chemical_list: D009004:Monosaccharide Transport Proteins; C426650:SLC35C1 protein, human