Leukocyte adhesion deficiency type II

Leukocyte adhesion deficiency type II (LAD II), also known as congenital disorder of glycosylation type IIc (CDG-IIc) or SLC35C1-CDG, is an extremely rare autosomal recessive primary immunodeficiency disorder caused by mutations in the SLC35C1 gene, which encodes a GDP-fucose transporter located in the Golgi apparatus. This defect leads to impaired fucosylation of glycoproteins, including selectin ligands (such as sialyl-Lewis X) on the surface of leukocytes. Without functional selectin ligands, leukocytes cannot properly roll along and adhere to blood vessel walls at sites of infection, resulting in a severely impaired immune response. Clinically, LAD II presents in infancy with recurrent severe bacterial infections, particularly of the skin, lungs, and gums, along with persistent leukocytosis (elevated white blood cell counts) even between infections. A hallmark feature distinguishing LAD II from LAD I is the presence of the Bombay blood group phenotype (absence of H antigen on red blood cells) due to the generalized fucosylation defect. Patients also typically exhibit intellectual disability, short stature, and distinctive facial features including a broad, flat nose and a long philtrum. Neurological involvement with psychomotor delay is a prominent feature. Treatment of LAD II includes aggressive management of infections with antibiotics and supportive care. Notably, oral fucose supplementation has been reported to improve the immunological defect in some patients by partially restoring selectin ligand expression and reducing infection frequency, though the neurological and developmental features may not respond as well. The response to fucose therapy appears to vary among patients, potentially depending on the specific underlying mutation. Unlike LAD I, bone marrow transplantation has not been widely employed for LAD II. Fewer than 10 cases have been reported worldwide, making this one of the rarest known primary immunodeficiencies.

Common questions about Leukocyte adhesion deficiency type II