Wiskott-Aldrich Syndrome | Overview
What is Wiskott-Aldrich syndrome?
Wiskott-Aldrich syndrome 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. It occurs mostly in males. According the National Institutes of Health, only 1 to 10 out of every 1 million boys has Wiskott-Aldrich syndrome.
The human immune system constantly patrols, protects and defends the body from all types of “enemies,” including bacteria, viruses and 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 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
- the white blood cells do not properly reach the sites of infections
Without normal immune cells, a child with Wiskott-Aldrich syndrome is at constant risk for:
- 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 Wiskott-Aldrich syndrome: 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 Wiskott-Aldrich syndrome are also at elevated risk for developing:
- autoimmune attack on the blood cells (autoimmune anemia, neutropenia or thrombocytopenia)
- inflammatory bowel disease (IBD)
- nephritis (kidney inflammation)
- vasculitis (inflammation of the blood vessels)
- other autoimmune diseases
- lymphoma and certain other cancers
There is more than one kind of Wiskott-Aldrich syndrome. The majority of boys 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 Wiskott-Aldrich syndrome, 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 Wiskott-Aldrich syndrome gene will develop the severe form of the disease or its milder variant, XLT. Moreover, also patients with XLT can progress to develop typical complications of Wiskott-Aldrich syndrome as they become older. Therefore, it is important that both patients with Wiskott-Aldrich syndrome and those with XLT be followed regularly by their doctor and by specialists in this disease.
How we care for 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 Wiskott-Aldrich syndrome 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.
Gene Therapy for Wiskott-Aldrich syndrome
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 Wiskott-Aldrich syndrome — 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. Learn more about the Gene Therapy Program.
Wiskott-Aldrich Syndrome | Symptoms & Causes
What are the symptoms of Wiskott-Aldrich syndrome?
Nearly every child with Wiskott-Aldrich syndrome will start showing symptoms as a baby, between the time they're born and the time they turn 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 Wiskott-Aldrich syndrome is a genetic disorder (caused by an error in the genes), it is always present at birth, however, symptoms may not show up until later in infancy.
What causes Wiskott-Aldrich syndrome?
Wiskott-Aldrich syndrome 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).
Wiskott-Aldrich syndrome 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 Wiskott-Aldrich syndrome 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, Wiskott-Aldrich syndrome almost always affects boys only.
Wiskott-Aldrich Syndrome | Diagnosis & Treatment
How is Wiskott-Aldrich syndrome diagnosed?
After gathering a complete medical history, your child's doctor may order one or more of the following tests to help diagnosis Wiskott-Aldrich syndrome:
- a test that measures the amount of platelets(clotting agents) in his blood
- a genetic test that reveals presence of a mutation in the Wiskott-Aldrich syndrome gene
- a blood test that demonstrates absence of the Wiskott-Aldrich syndrome protein in the white blood cells
- other blood tests as needed
Prenatal testing can also detect the gene mutation responsible for Wiskott-Aldrich syndrome.
If your child’s siblings are girls, it is extremely unlikely that they will also have Wiskott-Aldrich syndrome (though if she is a carrier, she can pass the mutation causing the disease on to her own sons). Because Wiskott-Aldrich syndrome 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 Hospital can help.
What are the treatment options for Wiskott-Aldrich syndrome?
Guarding against infection
Any child with Wiskott-Aldrich syndrome 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.
In general, families of children with Wiskott-Aldrich syndrome 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
Some of the standard childhood vaccinations are safe for children with Wiskott-Aldrich syndrome and some are not. Because their B-cells of children with Wiskott-Aldrich syndrome 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 Wiskott-Aldrich syndrome.
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
A stem cell transplant (also known as a bone marrow transplant) is the mainstay of treatment for Wiskott-Aldrich syndrome. 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 Wiskott-Aldrich syndrome, 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 Wiskott-Aldrich syndrome 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.
Stem cell transplants are not always perfect treatments for Wiskott-Aldrich syndrome. 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 Wiskott-Aldrich syndrome.
What is the 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 Wiskott-Aldrich syndrome or any other immune deficiency.