leukocyte adhesion deficiency 3

Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is a rare autosomal recessive disorder characterized by immune deficiency and bleeding problems. This condition results from mutations in the FERMT3 or KINDLIN3 gene, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells.

The immune defects associated with LAD3 are similar to those found in Leukocyte Adhesion Deficiency Type 1 (LAD1), while the bleeding tendency is comparable to Glanzmann thrombasthenia. This condition affects the ability of white blood cells to migrate to sites of infection and interact with foreign invaders, leading to recurrent bacterial infections.

Key features of LAD3 include:

• Recurrent bacterial infections without pus formation
• Major bleeding disorders
• Impaired wound healing

LAD3 is a rare and severe condition that requires prompt medical attention. If you or someone you know has been diagnosed with LAD3, it's essential to work closely with a healthcare professional to manage the condition and prevent complications.

References: * [8] Kindlin-3 is expressed in all hematopoietic cell types, in which it plays an important role in a variety of functions depending on integrin-mediated adhesion, such as platelet clot formation and leukocyte extravasation. * [9] Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is an autosomal recessive disorder characterized by LAD1-like immune deficiency and Glanzmann thrombasthenia-like bleeding problems. LAD3 results from mutations in FERMT3, or KINDLIN3, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells. * [11] Description. Leukocyte adhesion deficiency-3 (LAD3), also known as LAD1 variant (LAD1V), is an autosomal recessive disorder characterized by LAD1-like immune deficiency and Glanzmann thrombasthenia (GT; 273800)-like bleeding problems. LAD3 results from mutations in FERMT3, or KINDLIN3, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells. * [10] Leukocyte adhesion deficiency type III (LAD-III

Leukocyte Adhesion Deficiency Type 3 (LAD3) Signs and Symptoms

Leukocyte Adhesion Deficiency Type 3, also known as LAD-III or LAD-I variant, is a rare immunodeficiency disorder characterized by severe bacterial infections and a severe bleeding disorder. The signs and symptoms of LAD3 typically begin in infancy or early childhood.

• Life-threatening infections: Patients with LAD3 are prone to developing life-threatening infections, particularly those caused by bacteria such as Staphylococcus aureus.
• Glanzmann thrombasthenia-like bleeding tendency: Individuals with LAD3 exhibit a severe bleeding disorder similar to Glanzmann thrombasthenia, which can manifest as mucocutaneous bleeding.
• Abnormally increased size of the liver and spleen: Some patients may experience enlargement of the liver and spleen (hepatosplenomegaly).
• Reduced erythrocytes volume or hemoglobin concentration: LAD3 patients may have a reduced red blood cell count or hemoglobin level.

These symptoms can be severe and life-threatening, highlighting the need for prompt medical attention and treatment. [8][9]

References:

[8] A Chougule · 2023 — Mucocutaneous bleeding was the first clinical manifestation for all three of our patients with neonatal onset, similar to that reported in literature.

[9] Leukocyte adhesion deficiency (LAD) is a primary immunodeficiency that causes individuals to be abnormally susceptible to developing frequent soft-tissue infections, gum inflammation, and tooth loss. The white blood cells, or leukocytes, lack a protein on their surface, making them unable to enter infection sites and kill bacteria and other pathogens.

Leukocyte adhesion deficiency 3 (LAD3) is a rare genetic disorder characterized by impaired immune function and bleeding problems. Diagnostic tests for LAD3 are crucial for accurate diagnosis and management of the condition.

Blood Tests

A complete blood count (CBC) is often performed to detect leukocytosis, which is a common but nonspecific finding in LAD3 patients [1]. Specialized blood tests, including flow cytometry, can help diagnose LAD3 by detecting the absence or severe deficiency of adhesive glycoproteins on the surface of white blood cells (WBCs) [13][14].

Flow Cytometry

Flow cytometry is a laboratory test that uses monoclonal antibodies to detect specific proteins on the surface of WBCs. In LAD3 patients, flow cytometry can help identify the absence or severe deficiency of CD18/11a and 11b expression on monocytes, lymphocytes, and granulocytes [7].

Genetic Testing

Genetic testing is recommended for siblings of individuals with LAD3 to detect mutations in the FERMT3 gene, which encodes an intracellular protein that interacts with beta-integrins in hematopoietic cells [6][9]. This can help identify carriers and provide a definitive diagnosis.

Other Tests

In addition to these tests, other diagnostic procedures may be performed to rule out differential diagnoses. These include:

• Measurement of individual components by immunoprecipitation tests, ELISA, or Western blotting
• C3 serum levels
• Differential Diagnosis: Differentials for leukocyte adhesion deficiency include the following list of disorders [10]

It's essential to note that diagnosis of LAD3 is based on a combination of clinical symptoms and laboratory findings. A multidisciplinary approach involving pediatricians, hematologists, and geneticists can help ensure accurate diagnosis and management of this rare condition.

References:

[1] Chougule et al. (2023) - This article aims to highlight clinical and laboratory clues to the diagnosis of LAD-III, aiding prompt administration of prophylaxis and curative therapy of bacterial infections.

[6] Diagnosis is based on the clinical symptoms and on a complete blood count revealing neutrophilia. In LAD-I and LAD-II, flow cytometry should be performed for ...

[7] by A Chougule · 2023 — This article aims to highlight clinical and laboratory clues to the diagnosis of LAD-III, aiding prompt administration of prophylaxis and curative therapy of bacterial infections.

[9] by A Chougule · 2023 — This article aims to highlight clinical and laboratory clues to the diagnosis of LAD-III, aiding prompt administration of prophylaxis and curative therapy of bacterial infections.

[10] Measurement of individual components by immunoprecipitation tests, ELISA, or Western blotting. C3 serum levels. ... Differential Diagnosis. Differentials for leukocyte adhesion deficiency include the following list of disorders:

[13] Diagnosis includes testing for adhesive glycoproteins on the surface of white blood cells. Treatment is supportive, using prophylactic antibiotics and granulocyte transfusions and hematopoietic stem cell transplantation.

[14] Diagnosis includes testing for adhesive glycoproteins on the surface of white blood cells. Treatment is supportive, using prophylactic antibiotics and granulocyte transfusions and hematopoietic stem cell transplantation.

Leukocyte Adhesion Deficiency (LAD) III is a rare and severe immunodeficiency disorder, and the drug treatment for it is limited.

According to search results [6], Hematopoietic Stem Cell Transplantation (HSCT) is considered the only definitive treatment for LADIII. However, HSCT can have high rates of complications [6].

In terms of drug treatment, there are no specific medications that can cure LADIII. Instead, management focuses on controlling infections and includes symptomatic treatment with antibiotics and blood transfusions [8]. Researchers are also studying gene therapy as a potential treatment for individuals with LAD syndromes, including LADIII [7].

It's worth noting that the mainstay of treatment is supportive care, which may include prophylactic antibiotics and granulocyte transfusions, but these do not address the underlying cause of the disease [3]. In some cases, patients may be treated with trimethoprim/sulfamethoxazole for probable Pneumocystis jirovecii pneumonia [9].

Overall, while there are no specific drug treatments available for LADIII, researchers continue to explore new therapies, including gene therapy, to improve outcomes for individuals with this rare disorder.

Leukocyte adhesion deficiency 3 (LAD3) has several differential diagnoses that need to be considered for accurate diagnosis.

• Glanzmann thrombasthenia: This is a bleeding disorder caused by a deficiency in platelet glycoproteins IIb/IIIa, which can present with similar symptoms to LAD3, such as bruising and nosebleeds (epistaxis) [6][9].
• Leukemoid reaction: This is a condition characterized by an elevated white blood cell count, which can be seen in LAD3 patients. However, it is essential to distinguish between a leukemoid reaction and a true leukemia [1].
• Kindlin-3 deficiency: As mentioned earlier, LAD3 is caused by homozygous mutations in the FERMT3 gene, leading to Kindlin-3 deficiency. This can be distinguished from other conditions that affect adhesion molecules, such as LAD1 or Glanzmann thrombasthenia [5].
• Other neutrophil adhesion defects: There are several other conditions that can affect neutrophil adhesion, including IRAK-4 deficiency, autosomal dominant hyper IgE syndrome, chronic granulomatous disease, and neutrophil dysfunction. These conditions need to be ruled out through further testing [12][14].

To accurately diagnose LAD3, it is essential to consider these differential diagnoses and perform specific tests, such as detecting the absence or severe deficiency of adhesive glycoproteins on the surface of white blood cells using monoclonal antibodies (e.g., anti-CD11, anti-CD18) and flow cytometry [15].

References: [1] Context result 2 [5] Context result 3 [6] Context result 7 [9] Context result 9 [12] Context result 12 [14] Context result 14 [15] Context result 15