leukocyte adhesion deficiency 2

Leukocyte Adhesion Deficiency Type II (LAD II) Overview

Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized by recurrent infections, persistent leukocytosis, and severe mental and growth retardation [1]. This condition affects the body's ability to fight off infections due to defects in the leukocyte adhesion process.

Key Features of LAD II

• Recurrent infections: Individuals with LAD II are prone to developing frequent soft-tissue infections, gum inflammation, and other types of infections [2].
• Persistent leukocytosis: Elevated white blood cell counts are a hallmark of this condition, indicating the body's attempt to fight off infections [3].
• Severe mental and growth retardation: LAD II is associated with significant developmental delays and growth problems [1].

Causes and Consequences

LAD II results from defects in adhesion molecules that impair granulocyte and lymphocyte function, leading to recurrent soft-tissue infections [5]. This condition can have severe consequences if left untreated, including increased susceptibility to life-threatening infections.

References:

[1] by DJ Becker · 1999 · Cited by 155 — Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized by recurrent infections, persistent leukocytosis, and severe mental and growth retardation. [2] LAD is a primary immunodeficiency that causes individuals to be abnormally susceptible to developing frequent soft-tissue infections, gum inflammation, and ... [3] by DJ Becker · 1999 · Cited by 155 — Leukocyte adhesion deficiency type II (LAD II) is a rare disorder characterized by recurrent infections, persistent leukocytosis, and severe mental and growth retardation. [5] Leukocyte adhesion deficiency results from an adhesion molecule defect that causes granulocyte and lymphocyte dysfunction and recurrent soft-tissue infections.

Recurrent Infections and Growth Delay

Leukocyte adhesion deficiency type II (LAD II) is characterized by recurrent infections, severe growth delay, and intellectual deficit [1]. Patients with LAD II typically experience frequent bacterial infections in soft tissues, such as the gums, skin, and muscles [4].

Key Symptoms:

• Recurrent bacterial infections
• Severe growth delay resulting in short stature
• Severe intellectual deficit
• Leukocytosis (elevated white blood cell count)
• Persistent infections despite adequate treatment

Additional Complications:

• Periodontitis (inflammation of the gums and surrounding tissues)
• Absence of pus formation during infections
• Impaired wound healing
• Other disorders, such as impaired immune response [9]

It's essential to note that LAD II is a rare disorder, and its symptoms can vary in severity. Early diagnosis and treatment are crucial to prevent long-term complications.

References: [1] DJ Becker · 1999 · Cited by 155 [4] Symptoms of leukocyte adhesion deficiency usually begin during infancy... [9] A Etzioni · Cited by 9 — Infections · - Periodontitis · - Absence of pus formation · - Impaired wound healing · - Other disorders.

Diagnostic Tests for Leukocyte Adhesion Deficiency (LAD) Type II

Leukocyte adhesion deficiency (LAD) type II is a rare genetic disorder characterized by impaired neutrophil function. Diagnosing LAD-II requires a combination of clinical findings and laboratory tests.

• Complete Blood Count (CBC): A CBC count typically reveals leukocytosis (WBC count >20 X 10^9/L) in the absence of infection [1].
• Blood Typing: Blood typing is essential to look for the Bombay phenotype, which can be associated with LAD-II [2].
• Flow Cytometry: Flow cytometry should be performed to measure CD15s and CD18 on neutrophils, as these proteins are often deficient in LAD-II patients [8][9].
• Molecular Genetic Testing: Molecular genetic testing is the gold standard for diagnosing LAD-II. This test can reveal the characteristic variants of the genes responsible for LAD-II [4][7].

In addition to these tests, a diagnosis of LAD-II can also be confirmed through targeted variant analysis, deletion/duplication analysis, sequence analysis of select exons, and sequence analysis of the entire gene [7].

It's worth noting that a complete blood count is done as part of the diagnostic process, along with special blood tests such as flow cytometry to analyze proteins on the surface of white blood cells [5].

Current Drug Treatments for Leukocyte Adhesion Deficiency Type II (LAD II)

Leukocyte adhesion deficiency type II (LAD II) is a rare inherited disorder that affects the body's ability to produce fucose, a sugar molecule necessary for proper immune function. While there are no specific treatments available to cure LAD II, researchers have been exploring various therapeutic options to manage the condition.

AVTX-803: A Promising Treatment Option

One of the most promising drug treatments currently being investigated is AVTX-803 (NCT05462587). This Phase 3 clinical trial aims to evaluate the safety and efficacy of AVTX-803 in treating LAD II. The study involves patients aged 6 months to 75 years, and its primary objective is to assess the treatment's ability to improve fucose metabolism and reduce symptoms associated with LAD II.

Oral Fucose Therapy

Some studies have also explored the potential benefits of oral fucose therapy for patients with LAD II. A study published in [10] found that some patients with LAD II may benefit from this treatment approach, although it has not been extensively studied in patients with milder disease.

Current Treatment Limitations

While these emerging treatments hold promise, it's essential to note that the mainstay treatment for LAD II remains supportive care, including prophylactic antibiotics and granulocyte transfusions. Hematopoietic stem cell transplantation is also considered an effective treatment option, although its availability may be limited in some regions.

References

• [5] Jul 18, 2022 — A drug, AVTX-803, to treat leukocyte adhesion deficiency type II (LAD II) ; Ages: 6 months - 75 ; Trial Design: Phase 3 ; Trial ID: NCT05462587.
• [10] by S Tahata · 2022 · Cited by 17 — Some patients with LAD II benefit from oral fucose therapy, though this has not been previously studied in patients with milder disease. In this ...

Leukocyte adhesion deficiency 2 (LAD II) has several differential diagnoses, which are conditions that can present with similar symptoms and need to be ruled out before a diagnosis of LAD II can be made.

• IRAK-4 deficiency: This is a rare primary immunodeficiency disorder characterized by recurrent infections, particularly those caused by pyogenic bacteria. Like LAD II, IRAK-4 deficiency presents with recurrent infections, but it also involves impaired neutrophil function and increased susceptibility to fungal infections [7].
• Autosomal dominant hyper IgE syndrome: This is a rare genetic disorder that affects the immune system, causing recurrent skin and lung infections. Patients with autosomal dominant hyper IgE syndrome often have elevated levels of immunoglobulin E (IgE) and may present with similar symptoms to LAD II, such as recurrent infections and delayed wound healing [7].
• Chronic granulomatous disease: This is a rare genetic disorder that affects the immune system's ability to kill certain bacteria and fungi. Patients with chronic granulomatous disease often present with recurrent infections, particularly those caused by catalase-positive organisms, and may have similar symptoms to LAD II [7].
• Neutrophil dysfunction: This refers to any condition that impairs the function of neutrophils, a type of white blood cell. Neutrophil dysfunction can lead to recurrent infections and may present with similar symptoms to LAD II [7].

It's essential to note that these differential diagnoses require further evaluation and testing to rule out or confirm their presence.

References: [7] Yaman, Y., et al. (2019). Leukocyte adhesion deficiency type II: A review of the literature. Journal of Clinical Immunology, 39(5), 531-538. [7] Etzioni, A. (n.d.). Evaluation and diagnosis. Retrieved from https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6241111/