Congenital disorder of glycosylation type IIc

Congenital disorder of glycosylation type IIc, also called leukocyte adhesion deficiency type 2 or LAD2, is a rare inherited form of leukocyte adhesion deficiency. Its core defect is the absence of sialyl-LewisX on neutrophils, a ligand for the P- and E-selectin molecules on the lining of blood vessels, and it is associated with the SLC35C1 gene, which encodes a transporter of the sugar GDP-fucose into the Golgi apparatus. The condition was first recognised in two unrelated Israeli boys, aged 3 and 5, born to consanguineous parents. Both had severe intellectual disability, short stature, a distinctive facial appearance and the rare Bombay (hh) blood type, and both suffered recurrent bacterial infections such as pneumonia, periodontitis, otitis media and cellulitis, with a very high white blood cell count but no pus at the infected sites. Laboratory work showed that neutrophil movement was defective, and the cause was traced to impaired transport of GDP-fucose, which blocks the fucose-dependent sugar structures that white blood cells need to leave the bloodstream.