Wiskott-Aldrich syndrome: what is it, symptoms, treatment, prognosis

What is Wiskott-Aldrich Syndrome?

Wiskott-Aldrich Syndrome (SVO, eng. Wiskott – Aldrich syndrome, abbr. WAS) is a rare inherited disorder characterized by immunodeficiency and a reduced ability of the blood to form clots (thrombi). Signs and symptoms include easy bruising or bleeding due to a decrease in the number and size of platelets; susceptibility to infections, as well as to immune and inflammatory disorders; an increased risk of certain types of cancer (such as lymphoma). In addition, a skin condition known as eczema is common in people with WAS.

Wiskott-Aldrich syndrome is caused by mutations in a gene WAS and is inherited in the form of an X-bond. It primarily affects men.

Treatment may depend on the severity and symptoms of each case, but hematopoietic (hematopoietic) cell transplantation is the only known cure. Hematopoietic cells Are haematopoietic stem cells that can be found mainly in spongy material, inside bones (bone marrow), in the bloodstream (peripheral blood stem cells), and in the umbilical cord.

Over time, the prognosis of the disease has improved due to the effectiveness of this treatment. People who have undergone a successful and uncomplicated hematopoietic cell transplant generally have normal immune function and generally normal survival.

SVR is often considered part of a spectrum of diseases with two other disorders: X-linked thrombocytopenia and severe congenital neutropenia. These diseases have overlapping signs and symptoms and the same genetic cause.

Symptoms of Wiskott-Aldrich Syndrome

Almost every child with Wiskott-Aldrich Syndrome begins to show symptoms in infancy, between the time they were born and the time they turn one year old. Common signs and symptoms of SVO include:

• frequent and easily caused bleeding, which may occur:
  • from the nose;
  • from the mouth and gums;
  • in the stool.
• frequent and easy bruising (accumulation of blood in the subcutaneous tissue)
• a small, red rash of "dots" under the skin (called petechiae)
• chronic infections;
• eczema (atopic dermatitis);
• autoimmune diseases;
• anemia;
• arthritis;
• inflammatory bowel disease;
• nephritis;
• vasculitis.

Because Wiskott-Aldrich syndrome is a genetic disorder (caused by a mistake in the genes), it is always present at birth, but symptoms can only appear in infancy.

Complications

Complications associated with infection, bleeding, autoimmune diseases and malignant neoplasms.

Autoimmune and rheumatologic conditions may also occur. In one study, these conditions were found in 40% of patients, and often several conditions coexisted in the same patient. Patients with autoimmune disease developed significantly more malignant tumors. Another example - 55 patients with SVR from one hospital in France over 20 years - revealed autoimmune or inflammatory diseases in 72%, most often autoimmune hemolytic anemia among many other conditions.

Malignant tumors, especially lymphatic tumors, occur in 10-20% of patients with SVR.

How is Wiskott-Aldrich syndrome inherited?

SVO is caused by mutations (or changes) in a gene WASwhich produces the Wiskott-Aldrich syndrome protein (WASp). Gene WAS is located on the short arm of the X chromosome, so the disease is inherited in an X-linked recessive manner. This means that boys develop the disease, but their mothers or sisters, who may carry one copy of the disease gene, have no symptoms.

Because of X-related recessive inheritance, boys with SVO may also have maternal siblings (siblings) who are sick.

It is estimated that approximately one third of newly diagnosed SVR patients have no family history and are the result of new gene mutations that occur during conception. Determining the exact gene mutation in a patient with SVR can help immunologists predict how severe their symptoms might be.

In general, if the mutation is severe and almost completely affects the gene's ability to produce protein WAS, the patient develops a classic, more severe form of Wiskott-Aldrich syndrome. In contrast, insignificant production of mutated protein WAS, can lead to a milder form of the disorder.

Diagnostics

After collecting a complete medical history, the child's doctor may order one or more of the following tests to help diagnose Wiskott-Aldrich syndrome:

• a test that measures the number of platelets (clotting agents) in your blood;
• genetic test showing the presence of a mutation in a gene WAS;
• blood test showing no protein WAS in leukocytes;
• other blood tests as needed.

Prenatal testing can also detect a gene mutation responsible for Wiskott-Aldrich syndrome.

If a child has a sister, it is highly unlikely that she will also have Wiskott-Aldrich syndrome (although, if she is a carrier, she can pass on the disease-causing mutation on her own sons). Since SVO is a genetic disorder, it is recommended that you undergo genetic counseling for yourself and your other children.

Treatment for Wiskott-Aldrich syndrome

Any child with Wiskott-Aldrich Syndrome has a weakened immune system and is at serious risk of developing infections. This means that consistent and careful infection control measures are required. However, in many cases it may be sufficient to take simple precautions such as putting on a protective mask for the child to be protected before or between more complex procedures such as stem transplant cells.

Basic Precautions

In general, families of children with Wiskott-Aldrich Syndrome should take the following steps:

• observe a strict hand washing regimen for all family members and visitors;
• prescribe antibiotics, antifungals, or antiviral drugs as a preventive measure for a child;
• avoid walking with your child in crowded, dirty places or in the company of those who are sick;
• closely monitor for signs of a possible infection and, if it appears, see a doctor immediately;
• follow your doctor's recommendations for vaccinations.

Vaccinations for children

Some routine childhood vaccinations are safe for children with SVR, and some are not. Because B cells in children with SVR do not function properly, their bodies cannot produce normal antibodies that fight viruses, and some vaccines are actually live viruses, they pose too high a risk of infection to be safe for a child with a weakened immune system system.

However, other types of vaccines (against pneumococcus, Haemophilus influenzae, and meningococcus) are safe and may help prevent severe bacterial infections in patients with Wiskott-Aldrich syndrome.

Antibody infusions

Because the child's B cells may not produce antibodies against the infection, the child may need regular infusions (veins) of immunoglobulin.

Your child's doctor can advise you on the exact steps to take to reduce your risk of infection.

Protection against bleeding / bruising

Some measures to reduce the risk of uncontrolled bleeding and bruising may include:

• avoid activities that pose a significant risk of injury (for example, contact sports);
• Wearing a helmet when exercising that may pose a risk of head injury (such as cycling or skating)
• taking corticosteroids (medicines that help prevent allergic and inflammatory reactions, this is usually only done in an acute situation);
• immunoglobin infusion;
• platelet transfusions and spleen removal (usually only prescribed in an emergency).

Eczema management

Eczema is controlled with topical or systemic steroids and general, careful skin care.

Stem Cell / Bone Marrow Transplant

Stem cell transplantation (also known as bone marrow transplant) is the mainstay of treatment for Wiskott-Aldrich syndrome. This is the only treatment option available that can provide a complete cure.

Stem cells are a versatile cell type in the bone marrow. These cells have a unique and powerful ability: they can transform into several different types of specialized cells.

In the case of Wiskott-Aldrich syndrome, stem cells from a healthy donor are injected into the patient's bloodstream. These stem cells then become healthy white blood cells and platelets, which will replenish the function. blood and immune system - essentially creating a completely new, functional blood and immune system child. If platelets and the immune system regain full function, the baby can be cured permanently.

Not all children with SVR will recover after stem cell transplantation. The chances of success depend on:

• the general state of health of the child at the time of the procedure;
• matches between the patient and donor bone marrow (the best option is bone marrow taken from the corresponding brother or sister);
• the child's age at the time of transplant; ideally, the transplant should take place before he turns 5.

Gene therapy

Stem cell transplants are not always ideal for treating Wiskott-Aldrich syndrome. For example, children may have improved but not complete recovery of platelets to normal levels, or may have partial but not complete recovery of the immune system.

In addition, any graft carries the risk of a phenomenon known as graft versus host disease. This means that the new immune system coming from the donor attacks the patient's body as if it were an unwanted intruder. This condition is more likely to occur if the donor is from an unrelated person or if the tissue type is not fully matched. Some cases of graft versus host disease are mild, but others can be severe or even fatal.

A new and promising area gene therapycan have the answers to these treatment problems. In gene therapy, patients receive stem cells from their own bone marrow or blood (rather than from another person). These cells also have an additional ingredient: a working, healthy version of the mutated gene responsible for the child's illness is added to them.

If gene therapy is successful, the child will enjoy all the benefits of stem cell transplantation without the potential danger of graft versus host.

Forecast

In the past, the long-term prognosis has been poor. Before the use of stem cell transplantation, only a few patients survived after adolescence. age, and most of them died from the effects of bleeding, infection or malignant tumors. The median survival in the group of patients born after 1964 was 6.5 years, suggesting that survival continued to increase over time.

With aggressive care, the prognosis improved significantly. One study predicts an average survival rate of 25 years for patients undergoing splenectomy (surgery to remove spleen), and even longer - for patients who have successfully undergone bone marrow transplantation. Success rates across all categories of hematopoietic stem cell transplant (HSCT) have continued to rise over time. Now the overall survival rate after HSCT is about 90%.