Summary about Disease
Leukocyte Adhesion Deficiency (LAD) is a rare genetic disorder that affects the immune system. It is characterized by the inability of white blood cells (leukocytes) to properly migrate from the bloodstream to sites of infection. This defect impairs the body's ability to fight off bacteria, fungi, and other pathogens, leading to recurrent and life-threatening infections. There are three main types of LAD: LAD-I, LAD-II, and LAD-III, each caused by a different genetic defect. LAD-I is the most common form.
Symptoms
Symptoms of LAD vary depending on the severity of the condition but often include:
Delayed separation of the umbilical cord (typically separates around 2-3 weeks in LAD).
Recurrent bacterial and fungal infections, often involving the skin, mucous membranes, and respiratory tract.
Poor wound healing.
Persistent leukocytosis (high white blood cell count).
Gingivitis (inflammation of the gums) and periodontitis (gum disease).
Absence of pus formation at infection sites.
Causes
LAD is caused by genetic mutations that affect the production of adhesion molecules on the surface of leukocytes. These adhesion molecules are essential for leukocytes to stick to blood vessel walls and migrate into tissues to fight infection.
LAD-I: Mutations in the ITGB2 gene, which encodes the CD18 subunit of the beta-2 integrin family of adhesion molecules (LFA-1, Mac-1, p150,95). This is the most common type.
LAD-II: Mutations in the SLC35C1 gene, which is involved in the transport of fucose, a sugar molecule needed for the synthesis of selectin ligands on leukocytes.
LAD-III: Mutations in the FERMT3 gene, affecting kindlin-3, an intracellular protein required for integrin activation. All types of LAD are inherited in an autosomal recessive manner, meaning that both parents must carry a copy of the mutated gene for a child to be affected.
Medicine Used
Treatment for LAD focuses on preventing and managing infections.
Antibiotics: Used to treat bacterial infections. Often long-term prophylactic antibiotics are given.
Antifungals: Used to treat fungal infections.
Granulocyte Colony-Stimulating Factor (G-CSF): Can sometimes improve leukocyte function in some cases of LAD-I.
Bone Marrow Transplant (Hematopoietic Stem Cell Transplant): This is the only curative treatment for severe forms of LAD. It replaces the patient's defective immune system with a healthy one from a donor.
Gene Therapy: Under clinical development, gene therapy aims to correct the underlying genetic defect in LAD.
Is Communicable
No, Leukocyte Adhesion Deficiency is not communicable. It is a genetic disorder and cannot be transmitted from person to person.
Precautions
Precautions for individuals with LAD focus on minimizing the risk of infection:
Good hygiene: Frequent handwashing, proper dental care.
Avoidance of exposure to infections: Staying away from sick individuals.
Prompt treatment of infections: Seeking medical attention immediately at the first sign of infection.
Vaccinations: Consult with a doctor regarding appropriate vaccinations, as live vaccines may be contraindicated.
Careful wound care: Keeping wounds clean and covered to prevent infection.
Prophylactic antibiotics: Preventative antibiotic use may be prescribed.
How long does an outbreak last?
Since LAD is a genetic condition, not an infection, it doesn't have "outbreaks" in the traditional sense. Individuals with LAD are chronically susceptible to infections. The duration of an infection in someone with LAD will depend on the type of infection, its severity, and how quickly and effectively it is treated. Infections can be prolonged and severe due to the impaired immune response.
How is it diagnosed?
Diagnosis of LAD typically involves:
Complete Blood Count (CBC): Shows elevated white blood cell count (leukocytosis).
Flow Cytometry: Measures the expression of CD18 (in LAD-I) or selectin ligands (in LAD-II) on the surface of leukocytes. Reduced or absent expression confirms the diagnosis.
Genetic Testing: To identify the specific mutation in the ITGB2, SLC35C1, or *FERMT3* gene.
Functional Assays: Tests to assess leukocyte adhesion and migration.
Timeline of Symptoms
The timeline of symptoms varies depending on the severity of LAD.
LAD-I (Severe): Often presents in infancy with delayed umbilical cord separation, omphalitis (umbilical cord infection), and severe, recurrent infections.
LAD-I (Moderate): May present later in childhood with recurrent infections, poor wound healing, and periodontitis.
LAD-II: Typically presents in infancy with short stature, intellectual disability, and recurrent infections.
LAD-III: Presents with bleeding disorders, recurrent infections, and osteopetrosis. Symptoms may progress over time if not adequately managed.
Important Considerations
Genetic Counseling: Important for families with a history of LAD to assess the risk of having affected children.
Early Diagnosis: Crucial for initiating appropriate treatment and improving outcomes.
Infection Prevention: A key aspect of management to minimize morbidity and mortality.
Transplantation: Bone marrow transplantation offers the potential for a cure, especially in severe cases.
Multidisciplinary Care: Requires a team of specialists, including immunologists, hematologists, infectious disease specialists, and other healthcare professionals.
Research: Ongoing research is focused on developing new therapies, including gene therapy, to correct the underlying genetic defect in LAD.