Leukocyte adhesion deficiency II: therapy and genetic defect.
Leukocyte adhesion deficiency II (LAD II) is a rare congenital disease which is caused by a defect in fucosylation of glycoconjugates. Hypofucosylated structures include ligands for the selectin family of adhesion molecules. This results in a leukocyte adhesion defect causing an immunodeficiency. In addition, LAD II patients show severe mental and growth retardations suggesting a role of fucose in development. Recently, a LAD II patient was treated with oral supplementation of fucose. This simple therapy restored selectin ligands and corrected the immunodeficiency. However, in another patient the treatment protocol had no effect indicating that the biochemical defect in the latter patient is somewhat different. The genetic defect in LAD II has now been located to a gene encoding a GDP-fucose transporter which gates GDP-fucose into the Golgi where fucose is transferred onto glycoconjugates. Point mutations have been detected in this gene in several LAD II patients, which inactivate the transporter function. Thus, LAD II represents the first developmental and immune defect that is based on a malfunctioning nucleotide sugar transporter.
Wild
Martin K
MK
Institut für Zellbiologie, Zentrum für Molekularbiologie der Entzündung, Universität Münster, Münster, Germany. wildm@uni-muenster.de
Lühn
Kerstin
K
Marquardt
Thorsten
T
Vestweber
Dietmar
D
D002352:Carrier Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D019040:E-Selectin / Q000378:metabolism; D005643:Fucose / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006056:Golgi Apparatus / Q000378:metabolism; D006801:Humans; D007223:Infant; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics* / Q000628:therapy*; D009004:Monosaccharide Transport Proteins; D009504:Neutrophils / Q000166:cytology / Q000378:metabolism; D019007:P-Selectin / Q000378:metabolism; D011993:Recombinant Fusion Proteins
D002352:Carrier Proteins; D019040:E-Selectin; D009004:Monosaccharide Transport Proteins; D019007:P-Selectin; D011993:Recombinant Fusion Proteins; C426650:SLC35C1 protein, human; D005643:Fucose