Wiskott-Aldrich Syndrome: Types, Causes, Risk Factors, Diagnosis, Treatment and Complications

The rare inherited immunodeficiency Wiskott-Aldrich syndrome prevents a child's immune system from functioning properly. A child's risk of bleeding also rises since it makes it harder for their bone marrow to produce platelets.

It mostly affects men. According to the National Institutes of Health, Wiskott-Aldrich syndrome affects just 1 to 10 boys out of every million males. Human immune systems constantly defend the body against a variety of "enemies," such as bacteria, viruses, and parasites.

The bone marrow of a growing fetus produces the blood and immune system. All blood cells, including platelets, which control bleeding, and two immune cell types, T cells and B cells, which identify and combat perceived "invaders" and produce antibodies against infection, are eventually developed from bone marrow stem cells.

 Additionally, stem cells develop into many subtypes of white blood cells that are crucial for fighting infections. When a kid has Wiskott-Aldrich syndrome:

• T and B cells are present, but they don't function properly.
• The locations of infections are not properly reached by the white blood cells.

Types Of Wiskott-Aldrich syndrome

The Wiskott-Aldrich syndrome comes in several forms. Though some males experience X-linked thrombocytopenia (XLT), a lesser form of the condition, the majority of boys have the type known as the "classic" version. The same gene that is responsible for the classic Wiskott-Aldrich syndrome is defective in this condition, although the symptoms are substantially less severe.

Children who have X-linked thrombocytopenia typically have platelets that are excessively tiny in both size and quantity. Because of this, individuals struggle with simple bleeding and bruising but not other, more serious problems.

It is frequently challenging to anticipate whether a male infant born with a mutation in the Wiskott-Aldrich syndrome gene would experience the severe version of the condition or its milder counterpart, XLT. Furthermore, as individuals age, they may potentially advance to develop the classic Wiskott-Aldrich syndrome problems. It is crucial that patients with XLT and Wiskott-Aldrich syndrome receive regular medical care from their general practitioner and experts in this condition.

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Causes Of Wiskott-Aldrich syndrome

Wiskott-Aldrich syndrome is a hereditary condition (caused by a genetic error), hence it is typically present from birth, however, symptoms may not appear until later in infancy. The genetic disorder Wiskott-Aldrich syndrome results from a mutation, or defect, in the child's genes.

Genes are the small, intricately coded instructions that make up every living thing on Earth. They are what decide our appearance, our family tree, and how our features will be passed on to our offspring (and their offspring). There are times when the genes we receive from a parent also carry mutations or errors in the genetic code.

Mothers can pass on the X chromosome mutation to their sons if it affects the X chromosome, which is one of the two chromosomes, along with the Y, that determine gender. 

The mothers have two X chromosomes, therefore even if one of them is mutated, the other X chromosome still contains a normal copy of the gene, so the mutation has no physical effects on the mothers. 

However, they are able to pass on to their male offspring the X chromosome with the mutation and the illness it produces. Boys only have one X chromosome, thus male kids who receive the defective X chromosome from their mother will develop the condition. Even though the mother is not a carrier of the mutation, a male may occasionally be born with the faulty X chromosome (in this scenario, the mother's germ cell develops the mutation).

A mutation in a gene on the X chromosome causes Wiskott-Aldrich syndrome to appear. Since females have two X chromosomes and boys only have one, women who have a Wiskott-Aldrich syndrome gene deficiency in one of their X chromosomes are not affected by the condition (since they have a "healthy" X chromosome), but they can convey the defective gene to their male offspring. As a result, Wiskott-Aldrich syndrome almost always only affects boys.

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Symptoms of Wiskott-Aldrich syndrome

Between the time of birth and the age of one, nearly every kid with Wiskott-Aldrich syndrome will begin exhibiting symptoms. The following are typical warning signs and symptoms:

• Regular and simple bleeding that might happen from the nose, mouth, gums, and bowel movements
• A tiny red rash with "dots" under the skin that is frequently and easily bruised is known as petechiae.
• chronic illnesses
• Atopic dermatitis, often known as eczema
• Autoimmunity (vasculitis, nephritis, inflammatory bowel disease, anaemia, and arthritis)

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What Are The Risk Factors Associated With Wiskott-Aldrich Syndrome?

A child with Wiskott-Aldrich syndrome is constantly at risk for the following due to the absence of normal immune cells:

• Pneumonia
• Acne (atopic dermatitis)
• Sinus infections 
• Persistent, bloody diarrhoea
• Herpes, cytomegalovirus (CMV), Epstein-Barr virus (EBV), and numerous other forms of illnesses are viral in nature.

The additional feature of Wiskott-Aldrich syndrome makes these issues much more challenging: Platelets, the clotting components that prevent bleeding from going out of control, are not adequately produced by the child's body. Only a minimal amount of platelets are formed, and they are modest in size. The youngster is likely to endure frequent and difficult-to-control bleeding, even from the most minor bumps and scrapes, if their platelets are unhealthy. This bleeding might take place:

• In the bowel movements
• In the nose
• In the gums
• In the mouth
• Under the skin

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Diagnosis Of Wiskott-Aldrich syndrome

Your child's doctor may request one or more of the following tests after taking a thorough medical history to aid in the diagnosis of Wiskott-Aldrich syndrome:

• A blood test that counts the number of platelets (clotting factors) in his blood,
• A genetic test that indicates the presence of a mutation in the Wiskott-Aldrich syndrome gene
• A blood test that demonstrates the lack of the Wiskott-Aldrich syndrome protein in the white blood cells
• Additionally blood tests as necessary
• The gene mutation causing Wiskott-Aldrich syndrome can also be found during prenatal testing.

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Treatment Of Wiskott-Aldrich syndrome

It is exceedingly improbable that your child's female siblings will also have Wiskott-Aldrich syndrome (but if she is a carrier, she may carry the disease-causing mutation to her own sons).

Since Wiskott-Aldrich syndrome is a genetic condition, it is a good idea to inquire with your doctor about genetic counselling for you and your other children.

With a weakened immune system and a high risk of infection, Wiskott-Aldrich syndrome affects children in particular. This means that extensive and regular infection control procedures are required. To keep your child safe, however, before or between more extensive treatments, like a stem cell transplant, simple precautions like having him wear a protective mask, can sometimes be sufficient.

Simple Precautions

Families of children with Wiskott-Aldrich syndrome should generally take the following actions:

• All members of the family and guests must adhere to a rigid handwashing routine.
• As a preventive strategy, if recommended by the treating clinician, give the child antibiotics, antifungal, or antiviral medications. Also, keep the child away from crowded areas, unclean environments, and people who appear to be "coming down with something."
• Pay special attention to any indication of potential infection and seek quick medical attention.
• Adhere to the doctor's immunisation advice.
• Shots are given to children
• Wiskott-Aldrich syndrome children can receive some of the recommended childhood immunisations without any problems, but not all of them. Children with Wiskott-Aldrich syndrome's bodies are unable to develop the typical antibodies necessary to fight off viruses because their B cells do not work normally.
• A youngster with a compromised immune system shouldn't receive any vaccines because the live viruses in some of them represent too great a danger of illness.

Although they are safe, vaccines against pneumococcus, hemophilus, and meningococcus may assist people with Wiskott-Aldrich syndrome avoid serious bacterial infections.

Injecting antibodies

Your child may need regular infusions (injection through a vein) of the antibody immunoglobin, also known as immunological globin or gamma-globin, as his B cells might not create antibodies against infection.

Your child's doctor can give you specific instructions on what to do to lessen the risk of illness.

Protecting oneself from bruising and bleeding

Reduced risk of uncontrolled bleeding and bruising can be achieved through the following measures:

• Avoid engaging in dangerously traumatising activities, such as contact sports.
• wearing a helmet when engaging in physical activities that could result in head injury (like biking or skating)
• using corticosteroids (drugs that help reduce allergic and inflammatory reactions) (this is often only done in an emergency circumstance)
• Receiving transfusions of platelets, which are often only recommended in emergencies, receiving injections of the antibody immunoglobin
• The spleen is removed (this is typically only advised in an emergency)
• The treatment of eczema (atopic dermatitis)
• Eczema can be managed in a number of effective ways.

Transplantation of bone marrow and stem cells

Wiskott-Aldrich syndrome is typically treated with a stem cell transplant, also referred to as a bone marrow transplant.

This is the only course of treatment that has the potential of bringing about a long-term recovery.

In the bone marrow, stem cells, a flexible class of cells, are present. These cells have a distinct and potent ability that allows them to differentiate into a variety of specialised cell types.

When a child has Wiskott-Aldrich syndrome, stem cells from a healthy donor are put into the child's bloodstream. They will then develop into healthy white blood cells and platelets that restore blood and immune functions, basically creating a brand-new, fully-functional blood and immune system for the child. The youngster might be treated permanently if the immune system and platelets fully recover.

A stem cell transplant won't be beneficial for every child with Wiskott-Aldrich syndrome. The following factors affect the likelihood of success:

• Overall condition of the child at the time of the surgery
• The compatibility of the patient's and donor's bone marrow (marrow from a matched sibling is the best option).
• The child's age at the time of the transplant; ideally, it should happen before he turns five.
• One of the oldest, largest, and most seasoned paediatric transplant facilities in the country is the Dana-Farber/Boston Children's Cancer and Blood Disorders Center's Paediatric Stem Cell Transplant Programme. Every year, our specialists execute more than 90 transplants for children of various ages, with a wide range of medical issues, and from all over the world.

Gene therapy

Wiskott-Aldrich syndrome cannot always be fully treated with stem cell transplantation. For instance, children's platelets may improve but not fully return to a normal level, or their immune systems may partially but not fully heal.

Additionally, graft-versus-host disease is a danger associated with all transplants. This means that the patient's body is attacked by the donor's new immune system, which perceives the patient as an intruder. If the tissue type is not completely matched or the donor is unrelated, this disease is more likely to occur. Graft-versus-host disease might be modest in some cases or severe or even fatal in others.

Gene therapy is a relatively new and exciting field that may hold the solutions to various medical challenges. Patients obtain stem cells from their own blood or bone marrow during gene therapy (also known as gene transfer), as opposed to receiving stem cells from another individual. These cells also have an additional component: a functional, unharmed form of the gene that was altered and caused the child's illness has been introduced to them.

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Complications Of Wiskott-Aldrich syndrome

The following conditions are also more likely to occur in children with Wiskott-Aldrich syndrome as a result of these combined deficiencies:

• Autoimmune disease (autoimmune anaemia, neutropenia, or thrombocytopenia) that affects the blood cells
• Inflammatory bowel disease (IBD) 
• Arthritis
• Nephritis
• Vasculitis (blood vessel inflammation)
• Other autoimmune disorders
• Several additional cancers, including lymphoma

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