Have you ever wondered how your body fights an infection? The infection would be restricted to one spot, but your body would magically heal itself without you having to do much about it. Your white blood cells are responsible for this.
When there is a parasite or a foreign pathogen causing infection, the white blood cells fight the infection-causing organism and help you heal. The same happens for ulcers too. However, have you noticed your ulcers are not healing as quickly as before? Do they take more time to heal than doctors suggest they would? Could it be Leukocyte adhesion deficiency?
In This Article
- White Blood Cells – Your Body’s Defense
- What is Leukocyte Adhesion Deficiency?
- What Are the Types of Leukocyte Adhesion Deficiency?
- Signs And Symptoms in Children With Leukocyte Adhesion Deficiency
- Diagnosis of Leukocyte Adhesion Deficiency
- Can Leukocyte Adhesion Deficiency Be Prevented?
- How Do We Care For Children With Leukocyte Adhesion Deficiency?
White Blood Cells – Your Body’s Defense
White blood cells are part of your blood. They keep travelling through your body in your bloodstream and make up for 1% of your entire blood volume.
When an infection-causing organism enters your body, it starts damaging the healthy tissues and cells in that area. The white blood cells identify this invasion and amass an army of white blood cells to fight this infection. They produce antibodies to fight the infection, which eventually helps in curing you of the infection.
When you have ulcers – those sores on the surface of your skin that look inflamed and feel very sensitive to touch, your white blood cells respond. These ulcers can be seen in various parts of the body and the reason for them depends on which part of the body they occur.
While some ulcers that are big in size and deep can take time to heal, the smaller ones must heal quite quickly. However, if you notice your ulcers are taking way too much time to heal, it could be an issue with your leukocytes in the white blood cells.
What is Leukocyte Adhesion Deficiency?
Leukocyte Adhesion Deficiency (LAD) is an immune system disorder that reduces the effectiveness of the white blood cells, the leukocytes specifically. LAD syndromes are a set of disorders that are not common. They interfere with the way the white blood cells react and respond to an infection site.
LAD is an autosomal recessive disorder, meaning the child must have received two abnormal genes, one from each parent. Both the parents carry only one defective gene and are healthy. They are said to be carriers. However, when both the defective genes combine to make an embryo, the child inherits LAD.
LAD syndromes are severe immune deficiency disorders that can make a person more prone to infections. Since the white blood cells do not react as quickly or effectively as they are supposed to, the infections take longer than usual to heal.
What Are the Types of Leukocyte Adhesion Deficiency?
There are three main types of Leukocyte Adhesion Deficiency that can affect children and adults. Though all three types are of this immune deficiency, which has an impact on how the immune system protects the body against infections and various other pathogens, the three types of LAD have distinctive features to tell them apart.
1. LAD Type I
The LAD type 1 is one of the three types of this autoimmune deficiency and is characterised by the following symptoms.
a) Delayed Detachment of Umbilical Cord in NewBorn
One of the classic symptoms of LAD type 1 is the time taken for the umbilical cord to detach from the newborn’s body. Usually, the cord takes about 1-2 weeks to detach and fall off after birth. However, for babies with LAD, especially type 1, the umbilical cord will take 3 weeks or more to detach. In most cases, this delayed detachment is accompanied by infection in the umbilical cord stump.
[Read : When Will My Baby’s Umbilical Stump Fall Off?]
b) Skin And Mucous Membrane Infections
The type 1 LAD results in infections on the skin and the mucous membrane. The mucous membrane is the wet or moist lining you can feel around the insides of your nose and mouth. This lining reacts to any pathogen or foreign body that irritates it. This membrane is responsible for your sneeze and cough which are immediate reactions to some foreign pathogen trying to enter your body through your nose or mouth.
c) No Pus Formation
When you have an infection, it hurts, and then it becomes sore and ripe with pus. Often the formation of pus is the first indication for a layman that there is an infection. However, in type 1 LAD, you won’t see any pus.
When there is no pus formation, that means there is no sufficient reaction and work by the white blood cells in that infected spot. As a result, the infection will take more time to heal. When it takes more time to heal, the foreign pathogen is still in your body and can result in additional infections in other parts of the body as well.
d) Gingivitis
Children with type 1 LAD are at risk of developing Gingivitis, a severe inflammation of the gums, and periodontitis (tissues around the teeth). Severe inflammation of these areas can weaken the teeth and cause a loss of teeth – both primary and permanent.
2. LAD Type II
The bacterial and fungal infections are recurring in nature in type 2 LAD too. However, the infections are not as severe as in children with type 1 LAD. These infections are milder and are mostly treated as outpatient procedures. The infections are not life-threatening and do not require admission to the hospital or constant monitoring unless the infection has gone too deep or has resulted in other complications.
Just like in type 1 LAD, children suffering from type 2 LAD do not have pus formation at the infected site either. However, these children do not suffer from delayed umbilical cord detachment or infection of the umbilical cord stump.
Some of the other symptoms that set type 2 LAD apart from type 1 are:
a) Bombay Blood Type
This is a very unique and rare type of blood. Also known as HH blood type, was first discovered in Bombay, hence the name. This blood type is very unique. ABO is the most important classification of blood, which helps you understand a person’s blood type. ABO is used to group blood types. In the case of a transfusion, the ABO blood grouping is what helps identify the perfect donor match; a mismatch in this grouping can result in fatal outcomes.
b) Loss of Muscle Tone
The loss of muscle tone is also known as Hypotonia. The infant might appear to be limp at the time of birth and may struggle to keep their knees and arms bent. LAD type 2 can affect not only the muscle tone but also the muscle’s strength, motor skills, and the brain itself. This lack of muscle tone can be shown via the facial muscles that may appear very different.
c) Impact On Growth
LAD type II can impact the growth of the child. They may look very short and may not grow much. Their mental growth can be impacted too, resulting in mental retardation. Sometimes, this is evident in the early stages of life, and at times it may be visible only after a few years when the child does not attain growth milestones as expected.
3. LAD Type III
LAD type 3 is very different from type 1 LAD. Type 3 is caused by the mutation of a gene responsible for producing Kindlin3 – a protein that is important for activating integrins. When the integrins are not activated as expected, the leukocytes and platelets do not bind properly to the endothelium (inner lining of the blood vessels).
LAD 3 is a rare disorder and is not seen in many patients like the LAD type 1. Just like in type 1 and type 2 LAS, the type 3 patients will also suffer from recurring fungal and bacterial infections.
In addition to the frequent infections, children with type 3 LAD may also suffer from:
- Easy and profuse bleeding (especially after surgeries which can be life-threatening)
- Easy Bruising
- Nose bleeds
- Bleeding gums (Gingivitis)
- Large spots underneath the skin layer – red or purple in colour indicating bleeding in the subcutaneous region
Signs And Symptoms in Children With Leukocyte Adhesion Deficiency
Most children with LAD show symptoms and signs right from birth. Some of the common symptoms and signs you can see in patients with LAD are
- Umbilical Cord Detachment – The very first tell-tale sign that your child has LAD is the time the umbilical cord takes to detach. If it takes 3 weeks or more, and the stump gets infected after detachment, there are high chances that your child has type 1 LAD.
- Recurring Infections – When your child has recurring infections, it is advisable to get it checked right away by your doctor, rather than self-medicating.
- Recurring mouth sores and gingivitis.
- Ulcers that do not heal easily.
- Repeated ear infections.
- Bleeding – Due to the lack of protein to form blood clots, the child might suffer from frequent bleeds that don’t seem to stop immediately, as is the case with healthy children. This is only seen in LAD 3.
[Read : Recurrent Infections in My Toddler]
Diagnosis of Leukocyte Adhesion Deficiency
When your doctor realizes your child has been having recurring infections and bleeds that don’t seem to stop soon, they will ask for further tests to confirm a diagnosis of LAD. Further tests will help them determine which type of LAD your child is carrying.
1. Family History
Since LAD is an autosomal recessive disorder, both the parents must be carriers. The doctor will ask for the complete medical history of the parents. The parents are carriers and healthy on most occasions.
2. Testing For Adhesive Glycoproteins
When there is a severe deficiency or complete absence of the adhesive glycoprotein on WBC’s surface, it indicates a positive case of LAD. This test is done with the help of monoclonal antibodies and flow cytometry.
3. Blood Test
A complete blood test will show an increase in the levels of Neutrophils (a type of white blood cell) An increased white cell count can indicate LAD. White cell counts can increase to more than 1,00,000/mm3 in children with LAD (normal range – 4000 to 11,000/mm3).
4. Genetic Testing
Molecular genetic testing can help in confirming the diagnosis of LAD. This would also help in preventing your next child from getting the disease. To know more on this aspect, read this article (My child has a genetic immune deficiency – Can I prevent this disease in my next child).
Can Leukocyte Adhesion Deficiency be Prevented?
Leukocyte Adhesion Deficiency is an autosomal recessive disorder, meaning the child has received a defective gene from each parent. So, can you prevent it? Yes, and No.
If both parents are carriers of the LAD gene, there is a 25% chance their child may inherit both defective genes and develop LAD. There is no complete guarantee here, it is only by chance.
The mother can produce one normal egg and one egg with the defective gene. Similarly, the father can produce sperm with the defective gene and one healthy sperm. If the sperm with the defective gene fertilizes the egg with the defective gene, the child will inherit the LAD disease. If not, the child may either be healthy or just a carrier; meaning there are 3 out of 4 chances the child may not suffer from the disease.
LAD cannot be prevented in the first pregnancy, as parents would not know if they carried the defective gene. However, once the first child is diagnosed with LAD, genetic testing can be carried out in the fetus in the next pregnancy to determine if the baby is affected.
How Do We Care For Children With Leukocyte Adhesion Deficiency?
When your child is diagnosed with LAD, it can be a very stressful and difficult journey to care for a child with such a severe genetic disorder.
Here are a few tips to help you care for a child with LAD.
1. Prevent Infections
The best way to care for a child with LAD is to prevent infections. When you prevent infections, you can reduce the damage caused to various parts of the body over the years. Never let infected people near your child. Do not let them touch an infected spot as it can cause the infection to spread.
2. Hygiene
Teach them proper hygiene and ask them to stay safe and clean at all times.
3. Get Checked Immediately
If you notice your child is developing an infection, get it checked by the doctor immediately. Do not wait for a pus formation to be sure it is an infection. In most cases with LAD, there is no pus formation. You need to judge based on other symptoms only. Do not let the infection persist or delay treatment, as it can cause severe damage to various parts of the body, resulting in further complications.
4. Antibiotics
When an infection occurs or recurs, antibiotics can help cure the infection. However, it may take several weeks for the infection to resolve, unlike in healthy children.
5. Neutrophils Transfusion
In rare cases, this type of transfusion can help replace the defective white blood cells and help with LAD symptoms. This is used only as a rescue measure in rare situations.
6. Hematopoietic Stem Cell Transplant / Bone Marrow Transplant
For those suffering from LAD, the only possible treatment to cure the disease is a bone marrow transplant. With a bone marrow transplant, the genetic defects can be corrected. This transplant will be recommended for those with severe type 1 LAD and is mostly recommended in the early stages of life as the impact of the disorder is seen right from the time of birth.
[Read : Bone Marrow Transplant For Immune Deficiency in Children]
7. Follow-Up
The infections will be recurring in nature, and if left untreated, they can become severe in nature too. Always follow up with your doctor after infection, to ensure the infection is cured and your child is safe.
8. Regular Check-Ups
Regular check-ups and tests as recommended by your doctor will help keep infections in check. Catching the infections early and giving your child the right antibiotics can help cure them of the infections at the earliest.
9. Empathize
Be empathetic to the child who is unable to run around and play in the dirt like other regular children. Since they are prone to infections, they cannot be exposed to crowds and many other environments either. It can be hard to make a child understand. You need to be patient and persistent in the rules you put down for their safety.
If your child is diagnosed with LAD, you must consult a Pediatric Immunologist. Since it is a genetic defect passed down from both parents, the impact can be there right from birth. With proper care and immediate actions, you can help your child lead a healthy life. They may not be able to live a regular childhood as they are prone to infections. However, with a timely bone marrow transplant, most children with LAD can be cured completely and lead healthy life.
