What Is Wiskott-Aldrich Syndrome?

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Wiskott-Aldrich syndrome is a rare genetic and immunodeficiency disorder. It prevents the body’s immune system from properly protecting against infections and reduces the ability to form blood clots.

Usually diagnosed within the first year of life, babies and children with Wiskott-Aldrich syndrome experience abnormal bleeding episodes, more frequent infections, and an inflammatory skin condition known as eczema.

Caused by a genetic abnormality, Wiskott-Aldrich syndrome affects people born with male chromosomal makeup (XY) due to the sex chromosome X where the abnormal gene is located. It affects roughly one to 10 out of every 1 million newborn males.

Wiskott-Aldrich syndrome is named after the physicians who first discovered it. In 1934, German pediatrician Dr. Alfred Wiskott identified three brothers with the signature symptoms.

Almost two decades later, American pediatrician Dr. R.A. Aldrich confirmed that the condition is an inherited genetic abnormality. Researchers officially discovered the mutated gene and its location in 1994.

X chromosome with defective gene

Rasi Bhadramani / iStock / Getty Images

Wiskott-Aldrich Syndrome Symptoms

Wiskott-Aldrich symptoms usually start showing up anywhere from 6 months to 1 year of age, though as a genetic and primary immune deficiency condition, it’s technically present from birth. There are a few signature symptoms that will stand out in infants with Wiskott-Aldrich syndrome:

  • Abnormal and excessive bleeding from the mouth, nose, or bowels due to a decreased number of blood platelets (thrombocytopenia)
  • Frequent bacterial, viral, or fungal infections due to the immune system's inability to properly protect the body against harmful invaders
  • Red, itchy skin rash known as eczema

In addition, people with Wiskott-Aldrich syndrome have an increased risk for developing severe autoimmune disease (conditions where the immune system mistakenly attacks its own healthy cells) and have higher rates of cancers like lymphoma (a cancer of the immune system cells) and leukemia (blood cancer).

The severity of Wiskott-Aldrich syndrome and its symptoms can vary widely from person to person, even within the same family.

Causes

Genetic conditions like Wiskott-Aldrich syndrome happen because of an abnormality in the chromosomes, which is genetic material that make up our DNA. Specifically for Wiskott-Aldrich syndrome, the cause is a mutation in what’s known as the WAS gene.

WAS Gene

The WAS gene provides instructions for making a protein found in blood cells. It plays an essential role in signaling white blood cells to form immune responses to the surrounding environment—protecting the body against infections.

The mutation makes it so that the WAS genes cannot properly relay signals to white blood cells to protect the body with an immune response. This leads to the immune system issues related to Wiskott-Aldrich syndrome. In addition, white blood cells and platelets aren't able to clot properly, causing the condition's excessive bleeding episodes.

Inheritance Pattern

Wiskott-Aldrich syndrome affects people with a male (XY) chromosomal pattern because of the way it's inherited: through what's known as an X-linked pattern. This means the mutated gene is located on the X chromosome (a sex chromosome).

Because the male XY pattern has only one X chromosome, a mutation in just one copy of the gene is enough to cause the condition and its severe symptoms to occur.

Alternatively, people with a female chromosomal pattern (XX) have two X chromosomes. If there is a mutation present, they have a healthy X chromosome to fall back on.

It's pretty rare for females with the gene mutation to develop the symptoms and complications of Wiskott-Aldrich syndrome. When they do, it tends to be milder. Females are the "carriers" of the mutation and can pass the defective gene on to their children.

WAS Gene Mutations

It's worth noting milder forms of Wiskott-Aldrich syndrome exist, thanks to different mutations in the WAS gene. Some experts group Wiskott-Aldrich syndrome in with the following conditions under a broader category of "WAS-related disorders" because they all have the same underlying genetic cause:

Patients with milder forms of Wiskott-Aldrich syndrome won’t manifest the severe symptoms. Instead, they may present with more mild signs like low levels of neutrophils (a type of white blood cell), bruising, or recurrent infections, and they may not get a correct diagnosis right away due to a lack of prominent symptoms.

So far, researchers have discovered more than 300 mutations in the WAS gene.

Diagnosis

Early symptoms of Wiskott-Aldrich syndrome—such as excessive bleeding—may be mistaken for other conditions like the blood disorder idiopathic thrombocytopenic purpura (ITP) or even leukemia.

This is why your doctor will want to confirm a Wiskott-Aldrich diagnosis as quickly as possible, using two types of diagnostic tests that are performed in the laboratory:

  • Complete blood count (CBC): A complete blood count will measure the number and size of blood platelets present. Low numbers and small platelets are seen in the syndrome.
  • Flow cytometry: This test, done with a blood draw or cord blood, can determine the absence of a specific protein in the white blood cells seen in the condition. If so, a Wiskott-Aldrich syndrome diagnosis is likely.
  • Genetic testing: Genetic testing via a blood draw or biopsy is used to confirm whether a person has the mutated gene that leads to Wiskott-Aldrich syndrome. This can also be done before birth if there is a suspected gene carrier. Experts consider genetic testing the only way to provide a definitive Wiskott-Aldrich diagnosis.

Treatment

Following a Wiskott-Aldrich syndrome diagnosis, treatment plans will be based on the person’s specific condition. Treatment options for symptom reduction and prevention include:

  • Antibiotics and immunoglobulins: Because children with Wiskott-Aldrich syndrome are prone to getting infections, antibiotics can be a common treatment option. Regular doses of immunoglobulin (antibody) infusions provided by blood donors and given through IV can help cut down on the risk of infections in the first place.
  • Platelet transfusions: Excessive bleeding episodes may require a transfusion of blood platelets from a healthy donor. Healthy platelets can help blood clot more quickly in Wiskott-Aldrich patients.
  • Immunosuppressants: Immunosuppressants like corticosteroids help prevent the immune system from mistakenly attacking the body’s healthy cells. They may be suggested for Wiskott-Aldrich patients who develop autoimmune conditions.
  • Topical creams: Eczema rashes can be managed with prescription topical or oral steroids, or other prescription medications as needed.
  • Protective measures: Steps to guard against infection and uncontrolled bleeding may also be recommended, such as strict handwashing, wearing a protective mask, avoiding crowded environments, and wearing a helmet during physical contact activities or sports.

One treatment option has been identified as potentially providing a permanent cure: a bone marrow (stem cell) transplant. So far, experts say this is the most effective treatment for curing Wiskott-Aldrich syndrome.

It involves giving the patient new immune stem cells from a donor, allowing the patient's bone marrow to produce healthy, long-lasting immune cells. The patient must be "matched" with a donor, which could include a bit of a wait time if the patient's brother, sister, or other family member is not a match.

In addition, scientists and researchers are working on safely expanding gene therapy as a more widespread, promising cure for Wiskott-Aldrich patients. This process involves transplanting genetically modified stem cells from the patient’s own bone marrow and blood cells instead of from an outside donor.

As clinical trials are underway, the Boston Children's Hospital is one of the only medical facilities in the United States to offer this experimental therapy for Wiskott-Aldrich syndrome.

Vaccine Complications

Because Wiskott-Aldrich patients have compromised immune systems, experts recommend they do not receive live virus vaccines such as the measles, mumps, and rubella (MMR) vaccine. These vaccines contain an active (but weakened) virus, so there’s a potential they may cause infection in immunocompromised people.

On the other hand, inactivated vaccines—such as pneumococcal vaccines—can usually be given safely to Wiskott-Aldrich patients. But keep in mind they may not provide the full protection people with normal immune functions receive.

This is because people with immune deficiency disorders like Wiskott-Aldrich syndrome do not have normal protective antibody reactions to vaccines, so the response may not be as strong.

Prognosis

The earlier the diagnosis for Wiskott-Aldrich syndrome, the sooner treatment can begin to avoid further serious and potentially fatal complications.

With the inclusion of bone marrow transplantation as a treatment option, outcomes for Wiskott-Aldrich syndrome patients have improved greatly, allowing a normal life expectancy. Without any treatment, a patient's life expectancy can be cut short.

Additionally, Wiskott-Aldrich syndrome can take a toll on quality of life for the patient and family—affecting emotional, social, and cognitive functioning. But the good news is that some research has shown that patients with a bone marrow transplant reported better quality of life compared to those who had not received the treatment.

Know that your medical care team is available to help answer any questions you may have about treatment outcomes, in addition to providing suggestions for improving quality of life for the patient and family.

Coping

Dealing with a Wiskott-Aldrich syndrome diagnosis can be difficult, devastating, and frustrating for families. It’s helpful to know you don’t have to navigate this journey alone. Organizations like the Wiskott-Aldrich Foundation provide families with the educational and community support needed to improve understanding and awareness for this extremely rare condition.

Summary

Wiskott-Aldrich syndrome is a rare genetic condition. Babies with the syndrome have abnormal bleeding episodes, more frequent infections, and eczema. It is caused by a defective gene on the X chromosome and is seen in children with a male (XY) chromosomal pattern. A bone marrow transplant is an effective treatment.

A Word From Verywell

Symptoms like excessive bleeding and serious infections in babies and young children are scary for any parent to experience. Stay informed and actively involved with your child’s healthcare team. Early diagnosis and treatment lead to better outcomes.

Experts have made huge leaps in identifying bone marrow transplants as an effective, lifesaving treatment. Additionally, gene therapy as a potentially promising treatment on the horizon is a surely encouraging possibility for the future.

Frequently Asked Questions

What is the survival rate of children with Wiskott-Aldrich syndrome?

Wiskott-Aldrich syndrome outcomes and survival rates have made great strides over the past few decades. What was once considered to be a fatal disorder with a life expectancy of up to three years has turned into a treatable, manageable condition—with the right treatment and early intervention.

With a bone marrow transplant, Wiskott-Aldrich syndrome patients can be expected to survive a relatively normal lifespan—given there are no complications, and particularly if the transplant is done before the age of 2. Without a bone marrow transplant, life expectancy can decrease significantly.

Why do males develop Wiskott-Aldrich syndrome?

Simply speaking, males develop Wiskott-Aldrich syndrome because of where the gene mutation is located—on the X chromosome. People born with female biology have two X chromosomes, so if they carry a defect of the Wiskott-Aldrich syndrome gene in one of their X chromosomes, they don't develop the disease because they have another healthy X chromosome to rely on.

Because people born with male biology have only one X chromosome, if they inherit this from their mother, they will get the disease.

Can tests detect Wiskott-Aldrich syndrome before birth?

Yes, prenatal testing can detect the WAS gene mutation that causes Wiskott-Aldrich syndrome. A prenatal diagnosis can be life-saving, so this type of genetic testing is recommended for families carrying known mutations of the WAS gene before pregnancy or birth.

It allows parents the option to consider a cesarean (C-section) delivery to help avoid excessive bleeding at birth, and it can also help parents plan for early treatment measures.

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18 Sources
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  1. Blancas-Galicia L, Quiroz-Escamilla C, Yamazaki-Nakashimada MA. Wiskott-Aldrich syndrome: An updated review. Rev Alerg Mex. Oct-Dec 2011;58(4): 213-8.

  2. Jin Y, Wu J, Chen T, Chen J. When WAS gene diagnosis is needed: Seeking clues through comparison between patients with Wiskott-Aldrich syndrome and idiopathic thrombcytopenic purpura. Front Immunol. 2019;10:1549. doi:10.3389/fimmu.2019.01549

  3. Stanford Children's Health. Genetics and immune disorders.

  4. Boston Children's Hospital. Wiskott-Aldrich syndrome.

  5. MedlinePlus. WAS gene.

  6. National Institute of Allergy and Infectious Disease. Wiskott-Aldrich syndrome.

  7. MedlinePlus. Wiskott-Aldrich syndrome.

  8. Immune Deficiency Foundation. Wiskott-Aldrich syndrome.

  9. Buchbinder D, Nugent DJ, Fillipovich AH. Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments. Applying Clin Genet. 2014;7: 55-56. doi:10.2147/TACG.S58444

  10. St. Jude Children's Research Hospital. Wiskott-Aldrich syndrome.

  11. National Institutes of Health: National Center for Advancing Translational Sciences. Wiskott Aldrich syndrome.

  12. Bosticardo M, Ferrua F, Cavazzana M, Aiuti A. Gene therapy for Wiskott-Aldrich syndrome. Curr Gene There. 2014;14(6): 413-21. doi:10.2174/1566523214666140918103731

  13. Boston Children’s Hospital. Gene therapy gets in the ring with another disease. May 30, 2014. 

  14. Barberi I, Tiralongo V, Marsiglia L. Vaccination risks in children with rare diseases. Ital J Pediatr. 2015;41 (Suppl 2): A5. doi:10.1186/1824-7288-41-S2-A5

  15. Moratto D, Giliani S, Bonfim C, Mazzolari E, Fischer A, Ochs HD et al. Long term outcome and lineage-specific chimerism in 194 Wiskott-Aldrich syndrome patients treated by hematopoietic cell transplantation between 1980-2009: an international collaborative study. Blood. 2011;118: 1675-1684. doi:10.1182/blood-2010-11-319376

  16. Shah AJ et al. Quality of life of patients with Wiskott Aldrich syndrome and X-linked thrombocytopenia: a study of the Primary Immune Deficiency Consortium (PIDTC), Immune Deficiency Foundation, and the Wiskott-Aldrich Foundation J Clin Immunol. 2019 Nov;39(8):786-794. doi:10.1007/s10875-019-00689-2

  17. Zhao Q,e t al. Analysis of prenatal diagnosis for seven high-risk fetuses with Wiskott-Aldrich syndrome. Zhonghua Er Ke Za Zhi. 2012 Jan;50(1): 15-9.

  18. Liu N, et al. Mutation analysis of WASP gene and prenatal diagnosis of Wiskott-Aldrich syndrome. Zhonghua Er Ke Za Zhi. 2014 Sep;52(9): 662-6.