Leukocyte adhesion deficiency-I

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Synonyms

LAD1, LAD-I, Leucocyte adhesion deficiency type 1, Leukocyte adhesion molecule deficiency type 1,

Overview

Leukocyte adhesion deficiency type I (LAD-I) is a rare, inherited immunodeficiency disorder where white blood cells (leukocytes) struggle to adhere to blood vessel walls and migrate to infection sites. This deficiency leads to a range of serious health problems, primarily recurrent and severe bacterial and fungal infections

Symptoms

Delayed umbilical cord separation: The umbilical cord stump typically falls off within the first two weeks of life, but in infants with LAD-I, this separation can occur three weeks or later, often accompanied by inflammation and infection. 

Recurrent and severe infections: Bacterial and fungal infections are common, particularly in the skin, mucous membranes, and respiratory tract. 
Lack of pus formation: A hallmark of LAD-I is the absence of pus at infection sites. 

Poor wound healing: Wounds heal slowly and are prone to infection. 

Periodontitis and gingivitis: Children with LAD-I can develop severe gum inflammation and bone loss around the teeth, potentially leading to tooth loss. 
Leukocytosis: Individuals with LAD-I often have a higher than normal number of white blood cells in their blood

Causes

  • LAD-I is caused by mutations in the ITGB2 gene, which provides instructions for making a protein called CD18. CD18 is a crucial component of a larger protein called integrin, which helps leukocytes stick to other cells and tissues, including blood vessel walls.
  • When CD18 is absent or dysfunctional, integrins cannot properly form and function, hindering the ability of leukocytes to effectively fight infections

Diagnosis

  • Diagnosis is often based on a combination of clinical features, such as delayed umbilical cord separation and recurrent infections, and laboratory testing.
  • Flow cytometry, a blood test that analyzes leukocyte cell surface markers, is used to confirm the diagnosis by assessing CD18 expression

Prognosis

Prognosis depends on the severity of the disease. Without hematopoietic stem cell transplantation, death in patients with severe LAD-I occurs from infection within the first 2 years of life, whereas patients with a moderate form of the disease have abetter chance of surviving into adulthood. Survival rate after bone marrow transplantation is 75%.

Treatment

  • Prophylactic antibiotics:
    Patients with LAD-I often take antibiotics continuously to prevent infections.
  • Granulocyte transfusions:
    These transfusions provide a source of healthy white blood cells to help fight infections.
  • Hematopoietic stem cell transplantation:
    This is the most effective treatment for LAD-I and can be curative, particularly for severe cases.