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Wiskott-Aldrich Syndrome

  • Wiskott-Aldrich syndrome (WAS) is a very rare, serious and potentially life-threatening disorder that almost always affects boys. It causes a child to have a poorly functioning immune system – the body’s “defense center” against infection – and difficulty producing platelets , the blood cells that keep bleeding under control.

    When a child has WAS, he typically faces:

    • frequent bleeding, even from mild bumps and scrapes, that is hard to slow down or stop
    • eczema (atopic dermatitis)
    • repeated infections, including pneumonia, ear infections and sinus infections

    In addition, children with WAS are at elevated risk for developing:

    How Boston Children’s Hospital approaches Wiskott-Aldrich syndrome

    Boston Children’s has a long history of caring for children with complex disorders of the blood and immune system. Clinicians in Dana-Farber/Boston Children's Cancer and Blood Disorder Center and our Division of Allergy and Immunology are regarded as international leaders in understanding and treating rare conditions like Wiskott-Aldrich syndrome.

    The only known cure for WAS is a stem cell transplant (using as bone marrow, peripheral blood or umbilical cord blood from a healthy suitably tissue matched donor). Once introduced into your child’s bloodstream, the stem cells can develop into normal immune cells and platelets. The Stem Cell Transplant Center at Dana-Farber/Boston Children’s – one of the first and most renowned pediatric transplant centers in the nation – performs over 90 stem cell transplants each year. Our specialists not only conduct groundbreaking stem cell research and devise exciting new treatments; they also have a unique understanding of the special needs of the youngest, smallest patients.

    In addition, Dana-Farber/Boston Children’s has opened one of the first gene therapy clinical trials for children with WAS in the world and the only one in the United States. The clinical trial for WAS – which transplants genetically modified stem cells from a child’s own bone marrow or blood cells – may signify a promising new approach to fighting and defeating the disease.

  • What is Wiskott-Aldrich syndrome (WAS), and what does it have to do with my child’s immune system?

    WAS is a rare genetic immunodeficiency that keeps a child's immune system from functioning properly. It also makes it difficult for a child's bone marrow to produce platelets, making a child prone to bleeding. According the National Institutes of Health, only 1 to 10 out of every 1 million boys has WAS.

    The human immune system constantly patrols, protects and defends the body from all types of “enemies,” including:

    • bacteria
    • viruses
    • parasites

    The blood and immune system arises from a developing fetus’ bone marrow. Bone marrow stem cells eventually mature into all of the different blood cells, including platelets that control bleeding, and two immune cell types that play the important roles in warding off infection: T cells (white blood cells that identify and attack perceived “invaders”) and B cells (white blood cells that produce antibodies against infection). In addition, stem cells give rise to other types of white blood cells (neutrophils, macrophages, natural killer cells) that also play important roles in clearing infections.

    When a child has Wiskott-Aldrich syndrome:

    • the T cells and B cells are there but don’t work right
    • his white blood cells do not properly reach the sites of infections

    Without normal immune cells, a child with WAS is at constant risk for:

    • pneumonia
    • eczema (atopic dermatitis)
    • chronic, bloody diarrhea
    • ear and sinus infections
    • viral infections like herpes, cytomegalovirus (CMV) and Epstein-Barr virus (EBV)
    • many other types of infection

    These problems are further complicated by the other aspect of WAS: The child’s body does not properly produce platelets, the clotting agents that stop bleeding from getting out of control. The platelets that are produced are small and are only produced in small numbers. Without healthy platelets, the child is likely to experience frequent and hard-to-control bleeding, even from the mildest bumps and scrapes. This bleeding can occur:

    • under the skin
    • from the nose
    • from the gums and mouth
    • in bowel movements
    • in the brain

    As a result of these combined deficiencies, children with WAS are also at elevated risk for developing:

    There is more than one kind of WAS. The majority of boys with WAS have the type known as the “classic” form, though some experience a milder form of the disease known as X-linked thrombocytopenia (XLT). This is caused by a defect in the same gene involved in classic WAS, but the symptoms are much milder.

    Usually, children with X-linked thrombocytopenia have platelets that are overly small in both size and number. As a result, they have trouble with easy bleeding and bruising, but do not experience the other, more severe complications.

    However, it is often difficult to predict whether a male baby born with a mutation in the WAS gene will develop the severe form of the disease (WAS) or its milder variant, XLT. Moreover, also patients with XLT can progress to develop typical complications of WAS as they become older. Therefore, it is important that both patients with WAS and those with XLT be followed regularly by their doctor and by specialists in this disease.

    Your treating clinician can give you specifics about the form of WAS your child has.

    Is Wiskott-Aldrich syndrome treatable?
    The only proven treatment for Wiskott-Aldrich syndrome is a stem cell transplant (using bone marrow, peripheral blood or umbilical cord blood from a healthy, suitably matched donor). Because stem cells have the special ability to develop into other types of cells, a transplant can give the child’s body an essential new source of healthy white blood cells – rebuilding his immune system and allowing him to successfully ward off infections.

    Although WAS is a potentially life-threatening disease, there is hope: a timely diagnosis and prompt treatment make the condition very treatable in the vast majority of cases. You and your child are in the best possible hands. 

    Causes

    What causes Wiskott-Aldrich syndrome?
    WAS is a genetic disorder – meaning it is caused by a mutation, or error, in the child’s genes.

    Every living organism on this planet is made up of genes – tiny, complex coded instructions that determine what we look like, who we’re related to and how we’ll pass on our traits to our children (and our children’s children). Sometimes, the genes we inherit from a parent also contain mutations, or mistakes in the genetic code.

    When the mutation happens on the X chromosome – one of the two chromosomes, X and Y, that determine a person’s gender – it can be passed on by mothers to their sons. Because the mothers have two X chromosomes, even if they have a mutation on one of the two X chromosomes, they still have a normal copy of the gene on the other X chromosome, and therefore they themselves don’t experience any physical problems from the mutation. However they can transmit the X chromosome with the mutation – and the disease it causes – over to their male children. Boys have only one X chromosome, so male babies who inherit from their mother the faulty X chromosome with, will have the disease. Sometimes a boy can be born with the faulty X chromosome, even though his mother is not a carrier of the mutation (in this case, the mutation arises in the germ cell of the mother).

    WAS develops as the result of a defect in a gene located on the X chromosome. Because females have two X chromosomes, but males have only one, women who carry a defect of the WAS gene in one of their X chromosomes do not develop symptoms of the disease (because they have a “healthy” X chromosome), but can pass the defective gene on to their male children. As a result, WAS almost always affects boys only.

    Signs and symptoms

    What are the symptoms of Wiskott-Aldrich syndrome?
    Nearly every child with WAS will start showing symptoms as a baby, between the time he’s born and the time he turns 1. The symptoms usually include:

    • frequent and easy bleeding that can occur:
    • from the nose
    • from the mouth and gums
    • in bowel movements
    • frequent and easy bruising
    • a small red rash consisting of “dots” under the skin (these are called petechiae)
    • chronic infections
    • eczema (atopic dermatitis)
    • autoimmunity (anemia, arthritis, inflammatory bowel disease, nephritis, vasculitis)

    Since WAS is a genetic disorder (caused by an error in the genes), it is always present at birth. (Symptoms may not show up until later in his infancy, however.)

  • A diagnosis of Wiskott-Aldrich syndrome (WAS) is usually made based on:

    • a complete medical history and physical examination of your child
    • a test that measures the amount of platelets (clotting agents) in his blood
    • a genetic test that reveals presence of a mutation in the WAS gene
    • a blood test that demonstrates absence of the WAS protein in the white blood cells
    • other blood tests as needed

    Prenatal testing can also detect the gene mutation responsible for WAS.

    If your child’s siblings are girls, it is extremely unlikely that they will also have WAS (though if she is a carrier, she can pass the mutation causing the disease on to her own sons). Because WAS is a genetic disorder, it is a good idea to ask your doctor about genetic counseling for yourself and your other children. Learn how the Genetics Program at Boston Children’s can help.

  • Though Wiskott-Aldrich syndrome (WAS) is not a cancer, it is treated through Dana-Farber/Boston Children's Cancer and Blood Disorders Center because of our expertise in performing stem cell (bone marrow) transplants here.

    What are the treatment options for WAS?

    Guarding against infection
    Any child with WAS has a compromised immune system and is at serious risk of developing infections. This means consistent and thorough infection control measures are a must. However, in many instances, taking simple precautions, like having your child wear a protective mask, can be enough to keep him protected before or in between more involved treatments, like a stem cell transplant.

    Basic precautions

    In general, families of children with WAS should take the following steps:

    • follow a strict handwashing regimen for all family members and visitors
    • if advised by the treating clinician, administer antibiotics, antifungal or antiviral medications as a preventive measure for the child
    • avoid having the child in crowds, dirty places or in the company of anyone who is ill or seems to be "coming down with something"
    • watch closely for any sign of a possible infection and seek immediate medical attention
    • follow the clinician’s recommendations for vaccinations

    Childhood vaccinations

    Some of the standard childhood vaccinations are safe for children with WAS and some are not. Because their B-cells of children with WAS do not function properly, their bodies cannot produce the normal antibodies that fight off viruses. Since 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.

    However, other types of vaccines that are killed vaccines (against pneumococcus, hemophilus and meningococcus) are safe and may help prevent severe bacterial infections in patients with WAS.

    Antibody infusions
    Because your child's B cells may not produce antibodies against infection, he may need regular infusions (administration through a vein) of the antibody immunoglobin (also known as immune globin or gammaglobin).

    Your child's clinician can advise you about the exact steps you should be taking to help reduce the risk of infection.

    Guarding against bleeding/bruising
    Some measures for lowering the risk of uncontrolled bleeding and bruising can include:

    • avoiding activities that pose significant risks of trauma (such as contact sports)
    • wearing a helmet during physical activities that may pose a risk of head trauma (such as biking or skating)
    • taking corticosteroids (drugs that help prevent allergic and inflammatory responses) (this is usually done only in an acute situation)
    • receiving infusions of the antibody immunoglobin
    • receiving platelet transfusions (this is usually only prescribed in an emergency situation)
    • removing the spleen (this is usually only prescribed in an emergency situation)

    Managing eczema (atopic dermatitis)
    There are several useful ways of managing eczema. Learn more.

    Stem cell/bone marrow transplants
    stem cell transplant (also known as a bone marrow transplant) is the mainstay of treatment for WAS. This is the only available treatment option that has a chance of providing a permanent cure.

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

    In the case of a child with WAS, stem cells from a healthy donor are injected into the child's bloodstream. They will then become healthy white blood cells and platelets that replenish blood and immune functions – essentially building a whole new, functional blood and immune system for the child. If the platelets and immune system regain complete function, the child may be permanently cured.

    Not every child with WAS will benefit from a stem cell transplant .The odds of success depend on:

    • the child's overall health at the time of the procedure
    • the match between the patient and donor's bone marrow (the best option is marrow taken from a matched sibling)
    • the child's age at the time of the transplant; ideally, the transplant should take place before he turns 5 years old

    The Pediatric Stem Cell Transplant Center at Dana-Farber/Boston Children’s Cancer and Blood Disorders Center is one of the oldest, largest and most experienced pediatric transplant centers in the nation. Our experts perform more than 90 transplants for children of all ages, with a wide variety of health conditions and from all around the world, every year.

    Read about the process and what to expect during a stem cell transplant.

    Gene therapy
    Stem cell transplants are not always perfect treatments for WAS. For example, children may have improvement but not complete recovery of the platelets to a normal level or may have partial but not complete recovery of the immune system.

    In addition, any transplant carries a 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 is an unwanted intruder. This condition is more likely if the donor is an unrelated person or if the tissue type is not fully matched. Some cases of graft-versus-host disease are mild but others are severe or even fatal.

    A new and promising field, gene therapy, may have the answers to these treatment obstacles. In gene therapy (also called gene transfer), patients receive stem cells from their own bone marrow or blood (rather than from another person). These cells also have an added ingredient: they've been infused with a working, healthy version of the mutated gene responsible for the child's disease.

    If the gene therapy is successful, the child will enjoy all the benefits of a stem cell transplant without the potential hazard of graft-versus-host disease.

    Click on the Research tab above to learn more about our gene therapy clinical trial for children with WAS.

    Long-term Outlook

    If your child's blood and immune system is restored to good working order, he should be able to enjoy a rich, active adult life, including having a family.

    It is important to note, though, that genetic counseling is essential for prospective parents with a family history of WAS or any other immune deficiency.

    Helpful links

    Please note that neither Boston Children's Hospital, the Division of Allergy and Immunology, the Cancer and Blood Diseases Center nor the Dana-Farber/Children's Hospital Cancer Center Stem Cell Transplantation Program unreservedly endorses all of the information found at the sites listed below. These links are provided as a resource.

  • Our care is informed by our research, and our discoveries in the laboratory strengthen the care we provide at each child's bedside. Our scientific research program is one of the largest and most active of any pediatric hospital in the world.

    Généthon, the not-for-profit biotherapy laboratory funded by the French Muscular Dystrophy Association (AFM), and Boston Children’s have initiated a partnership to conduct an exciting new gene therapy (also called gene transfer) clinical trial for Wiskott-Aldrich syndrome (WAS).

    The U.S. portion of the trial is funded by the National Heart, Lung and Blood Institute (NHLBI) through its Gene Therapy Resource Program (GTRP). Principal investigators at Boston Children's are Sung-Yun Pai, MD, of Dana-Farber/Boston Children's Cancer and Blood Disorders Center, and Luigi Notarangelo, MD, director of the Research and Molecular Diagnosis Program on Primary Immunodeficiencies in the Division of Allergy and ImmunologyDavid A. Williams, MD, chief of the Division of Hematology/Oncology and director of Translational Research at Boston Children's, serves as sponsor-investigator.

    For more information about the study, and to find out if your child may be eligible to participate, please contact David Williams, MD (email), Luigi Notarangelo, MD (email) or Sung-Yun Pai, MD (email).

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