Congenital disorder of glycosylation type IIc or Leukocyte adhesion deficiency-2 (LAD2) is a type of
leukocyte adhesion deficiency
Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also kno ...
attributable to the absence of
neutrophil
Neutrophils (also known as neutrocytes or heterophils) are the most abundant type of granulocytes and make up 40% to 70% of all white blood cells in humans. They form an essential part of the innate immune system, with their functions varying ...
sialyl-LewisX, a ligand of
P- and
E-selectin
E-selectin, also known as CD62 antigen-like family member E (CD62E), endothelial-leukocyte adhesion molecule 1 (ELAM-1), or leukocyte-endothelial cell adhesion molecule 2 (LECAM2), is a selectin cell adhesion molecule expressed only on endothelial ...
on vascular
endothelium
The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...
. It is associated with ''
SLC35C1
GDP-fucose transporter 1 is a protein that in humans is encoded by the ''SLC35C1'' gene
In biology, the word gene (from , ; "... Wilhelm Johannsen coined the word gene to describe the Mendelian units of heredity..." meaning ''generation'' ...
''.
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
Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
. Similar to that in patients with LAD1, their infections were accompanied by pronounced
leukocytosis
Leukocytosis is a condition in which the white cell (leukocyte count) is above the normal range in the blood. It is frequently a sign of an inflammatory response, most commonly the result of infection, but may also occur following certain parasi ...
(30,000 to 150,000/mm
3) but an absence of pus formation at sites of recurrent
cellulitis
Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
. In vitro studies revealed a pronounced defect in neutrophil motility. Because the genes for the red blood cell
H antigen
H antigen can refer to one of various types of antigens having diverse biological functions. H antigen is located on the 19th chromosome in humans, and has a variety of functions and definitions as follows:
* Also known as substance H, H antigen ...
and for the secretor status encode for distinct α1,2-
fucosyltransferase
A fucosyltransferase is an enzyme that transfers an L-fucose sugar from a GDP-fucose (guanosine diphosphate-fucose) donor substrate to an acceptor substrate. The acceptor substrate can be another sugar such as the transfer of a fucose to a core G ...
s and the synthesis of Sialyl-LewisX requires an α1,3-fucosyltransferase, it was postulated that a general defect in
fucose
Fucose is a hexose deoxy sugar with the chemical formula C6H12O5. It is found on ''N''-linked glycans on the mammalian, insect and plant cell surface. Fucose is the fundamental sub-unit of the seaweed polysaccharide fucoidan. The α(1→3) li ...
metabolism is the basis for this disorder. It was subsequently found that GDP-L-fucose transport into
Golgi vesicles was specifically impaired, 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.
See also
*
Congenital disorder of glycosylation
A congenital disorder of glycosylation (previously called carbohydrate-deficient glycoprotein syndrome) is one of several rare inborn errors of metabolism in which glycosylation of a variety of tissue proteins and/or lipids is deficient or defect ...
*
Leukocyte adhesion deficiency
Leukocyte adhesion deficiency (LAD) is a rare autosomal recessive disorder characterized by immunodeficiency resulting in recurrent infections. LAD is currently divided into three subtypes: LAD1, LAD2, and the recently described LAD3, also kno ...
References
External links
Autosomal recessive disorders
Congenital defects of phagocyte number, function, or both
Rare diseases
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