Congenital disorder of glycosylation type IIc
| Congenital disorder of glycosylation type IIc | |
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| Other names | Rambam-Hasharon syndrome, CDG-IIc, CDG2C |
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| This condition ia inherited via autosomal recessive manner | |
Congenital disorder of glycosylation type IIc or Leukocyte adhesion deficiency-2 (LAD2) is a type of leukocyte adhesion deficiency attributable to the absence of neutrophil sialyl-LewisX, a ligand of P- and E-selectin on vascular endothelium.[1] It is associated with SLC35C1.[2]
This disorder was discovered in two unrelated Israeli boys 3 and 5 years of age, each the offspring of consanguineous parents. Both had severe mental retardation, short stature, a distinctive facial appearance, and the Bombay (hh) blood phenotype, and both were secretor- and Lewis-negative. They both had had recurrent severe bacterial infections similar to those seen in patients with LAD1, including pneumonia, periodontitis, otitis media, and localized cellulitis. Similar to that in patients with LAD1, their infections were accompanied by pronounced leukocytosis (30,000 to 150,000/mm3) but an absence of pus formation at sites of recurrent cellulitis. In vitro studies revealed a pronounced defect in neutrophil motility. Because the genes for the red blood cell H antigen and for the secretor status encode for distinct α1,2-fucosyltransferases and the synthesis of Sialyl-LewisX requires an α1,3-fucosyltransferase, it was postulated that a general defect in fucose metabolism is the basis for this disorder. It was subsequently found that GDP-L-fucose transport into Golgi vesicles was specifically impaired,[3] and then missense mutations in the GDP-fucose transporter cDNA of three patients with LAD2 were discovered. Thus, GDP-fucose transporter deficiency is a cause of LAD2.[4]
See also
[edit]References
[edit]- ^ Etzioni A, Harlan JM (2007). "Cell adhesion and leukocyte adhesion defects". In Ochs HD, Smith CI, Puck JM (eds.). Primary immunodeficiency diseases: a molecular and genetic approach. Oxford University Press. pp. 550–564.
- ^ Yakubenia S, Frommhold D, Schölch D, et al. (August 2008). "Leukocyte trafficking in a mouse model for leukocyte adhesion deficiency II/congenital disorder of glycosylation IIc". Blood. 112 (4): 1472–81. doi:10.1182/blood-2008-01-132035. PMID 18541720.
- ^ Sturla L, Puglielli L, Tonetti M, et al. (April 2001). "Impairment of the Golgi GDP-L-fucose transport and unresponsiveness to fucose replacement therapy in LAD II patients". Pediatr. Res. 49 (4): 537–42. doi:10.1203/00006450-200104000-00016. PMID 11264438.
- ^ Lübke T, Marquardt T, Etzioni A, Hartmann E, von Figura K, Körner C (May 2001). "Complementation cloning identifies CDG-IIc, a new type of congenital disorders of glycosylation, as a GDP-fucose transporter deficiency". Nat. Genet. 28 (1): 73–6. doi:10.1038/88299. PMID 11326280.
External links
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