Leukocyte Adhesion Deficiency (Type II) (LAD II)
What is Leukocyte Adhesion Deficiency Type II (LAD II)?
Leukocyte Adhesion Deficiency Type II (LAD II) (OMIM # 266265) is an autosomal recessive primary immunodeficiency characterized by impaired leukocyte motility and moderate to severe neurodevelopmental retardation. The genetic defect in LAD II patients has been shown to be various mutations in SLC35C1 gene which encodes for GDP-Fucose Transporter 1. This transporter mediates GDP-Fucose uptake into Golgi vesicles, and its dysfunction results in the absence of fucosylated glycans on the membranes of cells, leading to the loss of E- and P-selectin ligands on leukocytes. This loss of ligands results in the inability of circulating leukocytes to efficiently migrate to the sites of infection, which, in turn, causes persistent leukocytosis and recurrent, episodic life-threatening infections.
Simpler Terms
White blood cells fight microbes. In doing so, they need to adhere to the blood vessel wall to chase them. Some sugars, such as “Fucose”, help white blood cells to attach to the blood vessel. If something is wrong with the process of that sugar (i.e. fucose) being incorporated to white blood cells, no adherence occurs and white blood cells float free in the blood, unable to chase microbes. Consequently, microbes are now free to cause trouble in the body, causing infections in various locations from lungs to kidneys.
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Symptoms
Recurrent and intractable skin, lung, and periodontal infections are reported but are generally not life-threatening. Life-threatening infections may sometimes occur. The severity of infections may decrease with time, with adults primarily suffering from gum infections. Neurological problems are also important features of LAD II. Affected patients have severe intellectual disabilities, are short in stature, and have a distinctive facial appearance. Children have delays in daily functions, including sitting, walking, and speech. Based upon the few patients who have survived to adulthood, it seems that the immune problems dominate clinically in infancy, while the neurological problems become more prominent later in life.
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No-Cost Genetic Testing
AUG is partnered with NIH laboratory to provide no-cost genetic testing of the SLC35C1 gene.
If you suspect that you or a family member might have LAD II, talk to your doctor to see if genetic testing is right for you.
Genetic testing kits can be requested by your healthcare provider by emailing patientinfo@augtx.com.
Treatment and Management
There are currently no drugs approved for LAD II, but daily L-fucose has shown promise in patients based on case studies published in literature. AUG Therapeutics is currently running trials. If interested, please email us at patientinfo@augtx.com
Resources
Please note that these links are provided for informational purposes for patients, families, and healthcare providers. AUG is not affiliated with any of these institutions and does not endorse any particular resources.