What are the Different Types of LAD Syndrome?

Types of LAD Syndrome You Should Know

Leukocyte Adhesion Deficiency (LAD) is a rare condition where white blood cells, especially neutrophils, have trouble moving to areas in the body where there is an infection. This happens because of a problem with a special molecule that helps the cells stick to blood vessel walls and travel to the infection site.

As a result, people with LAD often get frequent and serious infections. LAD is a genetic disorder passed down from both parents (an autosomal recessive condition), meaning a person is born with it due to changes in their DNA. Furthermore, this disorder manifests in 3 different types, which give rise to unique symptoms, diagnostic methods, and treatment procedures.

Keep reading for detailed insight!

What are the Types of LAD and their Respective Symptoms?

The symptoms of LAD depend on its type:

LAD Type 1 (LAD-I)

• Recurrent, severe bacterial infections, especially of the skin and mucous membranes.
• Delayed separation of the umbilical cord.
• Fungal infections are common.
• Absence of pus at infection sites, a distinguishing feature.
• Delayed wound healing and increased scarring.
• Periodontitis (gum infection) and gingivitis develop after infancy, leading to tooth loss.
• Affected individuals may develop persistent sores around infected areas.
   

LAD Type 2 (LAD-II)

• Recurrent bacterial infections that are typically milder than LAD I.
• The frequency of infections often decreases after age 3.
• In older children, severe gum infections are seen.
   

LAD Type 3 (LAD-III)

• Recurrent bacterial and fungal infections, similar to LAD I.
• Bleeding problems typically present at birth
• Nosebleeds (epistaxis)
• Easy bruising

What Causes LAD?

LAD is a rare genetic disorder. It happens when certain genes don’t work properly, affecting how white blood cells fight infections.

● Causes of LAD Type I

It is caused by a mutation in the ITGB2 gene, which helps make a protein needed for white blood cells to stick to blood vessels and fight infection.

● Causes of LAD Type II

It is caused by a mutation in the SLC35C1 gene, which helps white blood cells move properly and recognize infection sites.

● Causes of LAD Type III

It is caused by a mutation in the gene for a protein called Kindlin 3, which is needed to turn on proteins (called integrins) that help white blood cells and platelets stick to blood vessels. In some cases, another gene called CalDAG-GEF1 may also be mutated.

How is LAD Inherited?

LAD is passed down in an autosomal recessive pattern. This means a child must get one faulty gene from each parent to have the disease. If both parents are carriers, there is:

• 25% chance the child will have LAD.
• 50% chance the child will be a carrier.
• 25% chance the child will not have the disease or be a carrier.

How is LAD Diagnosed?

LAD is typically diagnosed through a combination of the following clinical and laboratory methods:

1. Clinical Evaluation

Doctors begin by checking symptoms, medical history, and the pattern of infections. LAD may be suspected in infants with repeated infections, especially if there’s no pus at the infection sites and very high white blood cell counts.

2. Blood Tests

A complete blood count (CBC) is commonly used. It often shows high levels of neutrophils (a type of white blood cell). This condition is called neutrophilia and is a key sign of LAD.

3. Genetic Testing

LAD I, II, and III can be confirmed through molecular genetic testing. This test checks for mutations in specific genes:

• ITGB2 for LAD I
• SLC35C1 for LAD II
• FERMT3 (Kindlin 3) for LAD III
   

4. Prenatal Diagnosis (Before Birth)

A sample of the placenta is taken through a test called chorionic villus sampling (CVS). This helps check if the fetus has the same genetic mutation. LAD II can also be detected before birth by checking for the Bombay (hh) blood type. This test is done around 20 weeks of pregnancy.

What are the Treatment Options for LAD?

Treatment options for LAD include:

1. Antibiotic Therapy

It is an essential part of treatment for all types of LAD. Preventive antibiotics may be given to people with more severe forms, especially in LAD I.

2. Genetic Counseling

Helpful for families to understand the condition and assess the risk in future pregnancies.

3. Additional Treatments by LAD Type:

● LAD Type I

In moderate to severe cases, Ustekinumab is used, is not standard for LAD-I. Stem cell transplant (HSCT) is curative for severe cases. This helps control the chronic inflammation caused by the disease. In rare, life-threatening infections, granulocyte transfusions may be done.

● LAD Type II

Individuals usually respond well to regular antibiotics and careful monitoring.

● LAD Type III

People with serious bleeding problems may need blood transfusions to manage severe bleeding episodes. Infections are treated similarly to LAD I.

4. Supportive Care

Includes wound care, dental care (especially for periodontitis), and regular monitoring for infections.
 

Although Leukocyte Adhesion Deficiency is a genetic condition, early diagnosis is key to better outcomes. Regular medical follow-ups and supportive therapies play an important role in managing the condition in the long term. With the right support and medical guidance, those affected by LAD can lead fulfilling lives.