Introduction
Wiskott-Aldrich syndrome is a rare genetic, immunologic deficiency disorder that affects boys more than girls. It is characterized by an abnormal immune system and a reduced ability to form blood cells. It results from a genetic mutation in the gene enclosing Wiskott-Aldrich syndrome protein (WASp), affecting the immune system and causing immunodeficiency.
Babies and children with Wiskott-Aldrich syndrome are usually diagnosed within the first year of life as they experience abnormal bleeding episodes, more frequent infections, and inflammatory skin conditions (eczema).
What Is Wiskott-Aldrich Syndrome?
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Wiskott-Aldrich syndrome is a rare genetic and immunologic deficiency disorder. It prohibits the immune system from functioning against infections and reduces the ability of clot formation.
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Wiskott-Aldrich syndrome is caused by a genetic abnormality that involves people born on the male chromosome set (XY) because of the sex chromosome X, which carries the abnormal gene. It affects about one to ten out of every one million newborn males.
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Wiskott-Aldrich syndrome is named in honor of two physicians who first discovered it. German pediatrician Dr. Alfred Wiskott studied three brothers with the signature symptoms. Decades later, an American pediatrician Dr. R.A. Aldrich further confirmed that the condition is an inherited genetic abnormality.
What Causes Wiskott-Aldrich Syndrome?
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Genetic conditions such as Wiskott-Aldrich syndrome occur due to an abnormality in the chromosomes, which makes the genetic material for our DNA. In Wiskott-Aldrich syndrome, the cause is a mutation in the gene known as the WAS gene.
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The WAS gene stores instructions for synthesizing a protein found in blood cells. It signals white blood cells to produce immune responses against infections.
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The mutation causes difficulty for the WAS gene to relay signals to white blood cells. In addition, platelets lose their clotting ability, causing excessive bleeding episodes because it is pretty rare for females with the gene mutation to develop the symptoms and complications of Wiskott-Aldrich syndrome.
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Females are the mutation carriers and can pass the defective gene on to their children.
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Wiskott-Aldrich syndrome can also be grouped with the following conditions under a broader category of- WAS-related disorders because they all have the exact underlying genetic cause:
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X-Linked Thrombocytopenia- Accompanied by bruises and eczema on the skin.
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X-Linked Neutropenia- (Severe congenital neutropenia) causes frequent infections.
What Are the Symptoms of Wiskott-Aldrich Syndrome?
Wiskott-Aldrich symptoms start manifesting from 6 months to 1 year old; a genetic disorder is present from birth. However, some specific symptoms are visible in infants with Wiskott-Aldrich syndrome:
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Abnormal and Excessive Bleeding - A low number of platelets and small platelet size can lead to an increased tendency to bleed from the mouth, nose, or internal bleed (thrombocytopenia).
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Frequent Bacterial, Viral, or Fungal Infections - Due to the immune system's inability to adequately protect the body against harmful invaders.
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Eczema - Red, itchy skin rash (an inflammatory skin disease).
People who inherited the Wiskott-Aldrich syndrome are more prone to develop severe autoimmune diseases (conditions in which the immune system mistakenly destroys its own cells) and are susceptible to cancers like lymphoma (cancer of the lymphatic system) and leukemia (cancer of the blood). Some patients with Wiskott-Aldrich syndrome also suffer from autoimmune diseases, such as autoimmune hemolytic anemia (destruction of one’s red blood cells) or vasculitis (destruction and inflammation of blood vessels). The severity of this disease can vary remarkably, even within the same family. This is known as variable expressivity.
How Is Wiskott-Aldrich Syndrome Diagnosed?
Wiskott-Aldrich syndrome is a rare disorder that might get misdiagnosed in the initial phase of treatment, such as the blood disorder [idiopathic thrombocytopenic purpura (ITP) or even leukemia].
Wiskott-Aldrich diagnosis can be made using two types of diagnostic tests that are performed in the laboratory:
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Complete Blood Count (CBC) - A total blood count will measure the number and size of blood platelets. Less and smaller platelets are found with the syndrome.
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Flow Cytometry - This test is done with a blood draw that helps in determining the specific protein in the white blood cells whose absence points towards Wiskott-Aldrich syndrome.
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Genetic Testing - Genetic testing via a blood draw or biopsy confirms whether a person has the mutated gene that leads to Wiskott-Aldrich syndrome.
The critical laboratory findings for Wiskott-Aldrich syndrome relate to platelets. Determining platelet size and shape is essential. People with Wiskott-Aldrich syndrome typically have elevated levels of IgE (immunoglobulins for antibody production), and immune T cells are often abnormal.
How Is Wiskott-Aldrich Syndrome Treated?
Treatment of Wiskott-Aldrich syndrome after diagnosis is specific depending on their condition. Preventive treatment for symptom reduction includes:
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Antibiotics and Immunoglobulins - Regular doses of immunoglobulin (antibody) infusions provided by blood donors, given through IV, can help reduce the risk of infections in the first place.
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Platelet Transfusions - Loss of a large volume of blood requires urgent transfusion of blood platelets from a healthy donor. Healthy platelets help in the clotting of blood which is absent in Wiskott-Aldrich patients.
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Immunosuppressants - Immunosuppressants like Corticosteroids help with reducing the chances of destroying the body’s own cells. They are prescribed to patients who develop autoimmune conditions with Wiskott-Aldrich syndrome.
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Skin Creams - Eczema rashes can be managed with prescription topical or oral prescription medications as needed (oatmeal creams have shown calming effects on eczema skin).
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Protective Measures - Steps to protect against infection and uncontrolled bleeding are recommended, such as handwashing, wearing a protective mask, avoiding crowded areas, and wearing a helmet during physical contact activities or sports.
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Bone Marrow (Stem Cell) Transplant - Bone marrow is the tissue comprising the center of large bones. It is responsible for the generation of new blood cells. The treatment option has been identified as potential, providing a permanent cure.
What Are the Complications Seen With Wiskott-Aldrich Syndrome?
Wiskott-Aldrich patients have compromised immune systems; live virus vaccines are not recommended to them. This is because people with immunodeficiency disorder lack normal protective antibody reactions to vaccines, so the response against the live vaccine will be weak. At the same time, inactivated vaccines such as a pneumococcal vaccine are administered safely to Wiskott-Aldrich patients.
What Is the Prognosis for Wiskott-Aldrich Syndrome?
With the help of bone marrow transplantation, the prognosis for people suffering from Wiskott-Aldrich syndrome has significantly improved, allowing a normal life expectancy. Additionally, Wiskott-Aldrich syndrome can affect the quality of life for the patient and family, affecting emotional, social, and cognitive functioning.
Dealing with Wiskott-Aldrich syndrome can be difficult for families, too; however, it is helpful to know that you are not alone. Organizations like the Wiskott-Aldrich foundation try to help families with the knowledge and support needed to understand and generate awareness about this condition.
Conclusion
Wiskott-Aldrich syndrome is a rare genetic condition. Babies born with the syndrome have abnormal, uncontrolled bleeding episodes and skin conditions like eczema. Experts have made progress in identifying bone marrow transplants as an effective, lifesaving treatment.
It has been noted that Wiskott-Aldrich can be severe, and its associated symptoms can vary widely within the same family; people with milder forms of Wiskott-Aldrich syndrome will not manifest the severe symptoms. Instead, they will manifest milder symptoms like low levels of neutrophils (a type of white blood cell), bruising, or multiple infections.
