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$Unique_ID{BRK04335}
$Pretitle{}
$Title{Wiskott-Aldrich Syndrome}
$Subject{Wiskott-Aldrich Syndrome WAS Immunodeficiency with Thrombocytopenia
and Eczema Aldrich syndrome Eczema-Thrombocytopenia-Infection Syndrome
Immunodeficiency, Wiskott-Aldrich Type Immunodeficiency-2 IMD-2}
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Copyright (C) 1986, 1987, 1988, 1993 National Organization for Rare
Disorders, Inc.

76:
Wiskott-Aldrich Syndrome

** IMPORTANT **
It is possible that the main title of the article (Wiskott-Aldrich
Syndrome) is not the name you expected.  Please check the SYNONYMS listing to
find the alternate name and disorder subdivisions covered by this article.

Synonyms

     WAS
     Immunodeficiency with Thrombocytopenia and Eczema
     Aldrich syndrome
     Eczema-Thrombocytopenia-Infection Syndrome
     Immunodeficiency, Wiskott-Aldrich Type
     Immunodeficiency-2
     IMD-2

Information on the following diseases can be found in the Related
Disorders section of this report:

     Primary Agammaglobulinemias (X-Linked Immunodeficiency Syndrome)
     Severe Combined Immunodeficiency
     DiGeorge Syndrome
     Nezelof Syndrome
     Ataxia Telangiectasia

** REMINDER **
The Information contained in the Rare Disease Database is provided for
educational purposes only.  It should not be used for diagnostic or treatment
purposes.  If you wish to obtain more information about this disorder, please
contact your personal physician and/or the agencies listed in the "Resources"
section of this report.


Wiskott-Aldrich Syndrome is a rare inherited disorder (X-linked)
characterized by an immune deficiency primarily affecting B lymphocytes,
scaly red skin rashes (eczema), and abnormally low levels of circulating
blood platelets (thrombocytopenia).  The B lymphocytes are specialized white
blood cells of the immune system that search out and attack bacteria,
viruses, or other foreign substances in the body.  The symptoms of Wiskott-
Aldrich Syndrome may vary greatly among patients.  Children with this
disorder can face life-threatening complications of thrombocytopenia and
immunodeficiency prior to adulthood.

Symptoms

The symptoms of Wiskott-Aldrich Syndrome generally begin during infancy.
Excessive bleeding (hemorrhage) from circumcision or minor trauma is common
in infants with this disorder.  Bleeding may occur from the intestines and
hemorrhaging may be severe.  The skin may have small red spots (petechiae)
and/or purplish discolorations due to the leakage of blood under the skin
(thrombocytopenic purpura).  In addition, infants with Wiskott-Aldrich
Syndrome may have chronic red, scaly rashes on the skin (eczema).

Male children with Wiskott-Aldrich Syndrome have defects in their
resistance to infections.  These defects occur because of the inability of T
lymphocytes to properly resist infectious disease (cell-mediated immunity).
T lymphocytes, also known as "killer cells," assist B lymphocytes to respond
to infection and other foreign agents that invade the body.  Defects also
occur in the development and the continuing presence of circulating
antibodies in the blood (humoral immunity).

The most outstanding immune defect in infants with Wiskott-Aldrich
Syndrome is the inability to produce antibodies to certain complex
carbohydrates (polysaccharide antigens).  Children with this disorder are
highly susceptible to infections with particular organisms that have
coverings or are "encapsulated," since these coverings contain
polysaccharides.  These encapsulated organisms include pneumococcus and
Hemophilus influenzae.  Children with Wiskott-Aldrich Syndrome commonly
experience infections of the middle ear (otitis media), acute inflammation of
the lungs (pneumonia), inflammation of the membranes that cover the brain and
spinal cord (meningitis), and systemic infection with bacteria present in the
blood stream (sepsis).

Cell-mediated immunity and T cell function become progressively worse as
a child with Wiskott-Aldrich Syndrome ages.  Fungal and viral infections can
become serious problems late in the course of the disorder.  Pneumocystis
carinii (a bacteria that causes pneumonia) and herpes virus infections are
also common.

Other symptoms of Wiskott-Aldrich Syndrome include an abnormally enlarged
spleen (splenomegaly) and anemia.  People with this disorder have a 10
percent chance of developing malignancies, particularly leukemia and
lymphoma.  (For more information on these disorders, choose "Anemia,"
"Leukemia," and "Lymphoma" as your search term in the Rare Disease Database.)

People with Wiskott-Aldrich Syndrome have normal levels of total
antibodies in their blood; however, the proportions of different antibodies
are abnormal.  Cells that later produce platelets (precursors) appear normal
under a microscope, but platelets circulating in the blood stream have both
structural and functional abnormalities.

Causes

Wiskott-Aldrich Syndrome is inherited as an autosomal recessive X-linked
genetic trait.  Human traits, including the classic genetic diseases, are the
product of the interaction of two genes, one received from the father and one
from the mother.  X-linked recessive disorders are conditions which are coded
on the X chromosome.  Females have two X chromosomes, but males have one X
chromosome and one Y chromosome.  Therefore, in females, disease traits on
the X chromosome can be masked by the normal gene on the other X chromosome.
Since males only have one X chromosome, if they inherit a gene for a disease
present on the X, it will be expressed.  Men with X-linked disorders transmit
the gene to all their daughters, who are carriers, but never to their sons.
Women who are carriers of an X-linked disorder have a fifty percent risk of
transmitting the carrier condition to their daughters, and a fifty percent
risk of transmitting the disease to their sons.

The defective gene that causes Wiskott-Aldrich Syndrome is located on the
short arm of the X chromosome (p11.4-p11.21).  Males get the more severe form
of the disorder.

Affected Population

Wiskott-Aldrich Syndrome is a rare disorder that affects more males than
females.  Females can get a milder form of the disorder, or be a carrier with
no symptoms.

Related Disorders

Symptoms of the following disorders can be similar to those of Wiskott-
Aldrich Syndrome.  Comparisons may be useful for a differential diagnosis:

Primary Agammaglobulinemias (X-linked Immunodeficiency) are a group of
inherited immune deficiencies characterized by insufficient antibodies.  The
most frequent symptoms of these disorders are usually repeated bacterial
infections.  Bacteria infections are a frequent cause of chronic inflammation
of the intestines and diarrhea.  Repeated infections of the middle ear and
respiratory tract may also occur.  Areas of patchy, reddish skin may appear
around the eyes, fingers, knees, and ankles.  Some children with Primary
Agammaglobulinemias experience joint swelling and pain.  (For more
information on this disorder, choose "Primary Agammaglobulinemias" as your
search term in the Rare Disease Database.)

Severe Combined Immunodeficiency (SCID) is a group of rare, congenital
disorders characterized by little or no immune response.  A person with this
disorder is susceptible to recurring infections with bacteria, viruses,
fungi, and other infectious agents.  If untreated, this disorder may result
in frequent, severe infections, growth retardation, and can be life-
threatening.  Other symptoms of this disorder may include weight loss,
weakness, infections of the middle ear, and skin infections.  (For more
information on this disorder, choose "Severe Combined Immunodeficiency" as
your search term in the Rare Disease Database.)

DiGeorge Syndrome is a very rare immune deficiency that results from
developmental defects in the thymus and parathyroid glands.  This disorder is
characterized by seizures during the first few days of life due to the
abnormal function of the parathyroid gland.  Inability to fight off frequent
infections from viruses, fungi, and other bacteria is characteristic of this
disorder.  Children with DiGeorge Syndrome frequently have chronic nasal
infections, diarrhea, oral candidiasis, and Pneumocystis pneumonia.  (For
more information on this disorder, choose "DiGeorge" as your search term in
the Rare Disease Database.)

Nezelof Syndrome is a rare immune deficiency disorder characterized by
the impairment of cellular immunity against infections.  Symptoms of this
disorder may include frequent and severe infections from birth including oral
candidiasis, diarrhea, skin infections, septicemia, urinary tract infections,
measles, pulmonary infections, and vaccinia.  Typically a child with this
disorder may be mentally retarded and have a progressive loss of muscle
tissue.  (For more information on this disorder, choose "Nezelof" as your
search term in the Rare Disease Database.)

Ataxia Telangiectasia is a severe, rare, inherited neurological disorder
characterized by the progressive loss of motor coordination in the arms,
legs, and head (cerebellar ataxia).  Some cases of this disorder are
associated with immunodeficiencies (IgA or IgE).  Mental development may be
normal in the early stages of the disease, but progressive dementia may
occur.  This disease usually begins in infancy but may not be apparent until
the child is school age.   Classic red spots or telangiectasia appear in the
eyes, and later on the face and roof of the mouth.  (For more information on
this disorder, choose "Ataxia Telangiectasia" as your search term in the Rare
Disease Database.)

Therapies:  Standard

Children with Wiskott-Aldrich Syndrome are treated regularly with transfer
factor, a substance derived from lymphocytes.  About 50 percent of patients
experience a restoration of the proper function of blood cells and the immune
system.  This factor also improves the itchy red rashes (eczema) associated
with this disorder.

Researchers are studying bone marrow transplantation from a compatible
donor (allogenic) as a possible treatment for some cases of Wiskott-Aldrich
Syndrome.  Patients treated with this procedure receive high doses of
chemotherapy, followed by radiation therapy.  Then donor bone marrow cells
are given intravenously to the patient.  It is hoped that this procedure may
lead to the improvement of the blood abnormalities and immune deficiencies
associated with Wiskott-Aldrich Syndrome.  A complication of this procedure
may be Graft versus Host Disease, has also been used with some success in a
few patients.  (For more information on this disorder, choose "Graft versus
Host" as your search in the Rare Disease Database.)

Children with Wiskott-Aldrich Syndrome who do not respond well to
transfer factor, are given antibodies intravenously and antibiotics that may
help reduce susceptibility to infectious disease.  Excessive abnormal
bleeding, a complication of thrombocytopenia, may be managed by administering
carefully purified platelet concentrates or the surgical removal of the
spleen (splenectomy).  While effective in reducing the risk of bleeding,
splenectomy further increases the risk of serious infection with a variety of
organisms.  Most of the patients will require continued intravenous
antibiotic and/or gammaglobulin treatment to prevent infections.  Platelet
transfusions are not without problems, since repeated transfusions are likely
to stimulate the formation of platelet antibodies.  The standard drugs for
thrombocytopenia, corticosteroids and immunosuppressants, have no role in
the treatment of Wiskott-Aldrich Syndrome since these drugs cause a further
decrease in immune function.

Vincristine may be a useful drug in the treatment of cancer associated
with this disorder, since it has anti-tumor activity and helps improve
platelet function.  Vincristine does not suppress the immune system.

Infectious disease in children with Wiskott-Aldrich Syndrome requires
vigorous therapy with antifungal, antibiotic, and supportive measures.
Pneumonia caused by Pneumocystis carinii can be particularly difficult to
treat; the 2 drugs usually used are trimethoprim-sulfamethoxazole and
pentamidine isethionate.  (For more information on treatment of P. carinii
pneumonia, choose "AIDS" as your search term in the Rare Disease Database.)
Cytomegalovirus and generalized herpes simplex infections may be treated with
acyclovir, ganciclovir (DHPG), idoxuridine, floxuridine, or cytarabine.
Severe Candida and related fungal infections usually respond well to
amphotericin B therapy.  (For more information on this disorder, choose
"Cytomegalovirus" as your search term in the Rare Disease Database.)

Prevention of infection is extremely important.  Every attempt should be
made to protect people with Wiskott-Aldrich Syndrome from infectious disease.
Immunization with live virus vaccines should probably be avoided.

Genetic counseling will be of benefit for patients and their families.
Other treatment is symptomatic and supportive.

Therapies:  Investigational

Scientists are studying the role and functions of genes through the National
Institutes of Health's Human Genome Project.  It is hoped that they may
identify the protein that is defective in Wiskott-Aldrich Syndrome so that a
treatment may be developed to correct the genetic abnormality that causes
this disorder.

This disease entry is based upon medical information available through
June 1993.  Since NORD's resources are limited, it is not possible to keep
every entry in the Rare Disease Database completely current and accurate.
Please check with the agencies listed in the Resources section for the most
current information about this disorder.

Resources

For more information on Wiskott-Aldrich Syndrome, please contact:

     National Organization for Rare Disorders (NORD)
     P.O. Box 8923
     New Fairfield, CT  06812-1783
     [phone]

     Immune Deficiency Foundation
     3565 Ellicott Mill Drive, Unit B2
     Ellicott City, MD  21043
     [phone]
     [phone]

     NIH/National Institute of Allergy and Infectious Diseases (NIAID)
     9000 Rockville Pike
     Bethesda, MD  20892
     [phone]

     NIH/National Cancer Institute (NCI)
     9000 Rockville Pike, Bldg. 31, Rm. 1A2A
     Bethesda, MD 20892
     (800) 4-CANCER

The National Cancer Institute has developed PDQ (Physician Data Query), a
computerized database designed to give doctors quick and easy access to many
types of information vital to treating patients with this and many other
types of cancer.  To access this service, a doctor can contact the Cancer
Information Service offices at 1-800-4-CANCER.  Information specialists at
this toll-free number can answer questions about cancer prevention,
diagnosis, and treatment.

For Genetic Information and Genetic Counseling Referrals:

     March of Dimes Birth Defects Foundation
     1275 Mamaroneck Avenue
     White Plains, NY 10605
     [phone]

     Alliance of Genetic Support Groups
     35 Wisconsin Circle, Suite 440
     Chevy Chase, MD  20815
     (800) 336-GENE
     [phone]

References

MENDELIAN INHERITANCE IN MAN, 10th Ed.:  Victor A. McKusick, Editor:  Johns
Hopkins University Press, 1992.  Pp. 1781-83.

CECIL TEXTBOOK OF MEDICINE, 19th Ed.:  James B. Wyngaarden, and Lloyd H.
Smith, Jr., Editors; W.B. Saunders Co., 1990.  Pp. 1451-52, 1578.

THE MERCK MANUAL, 16th Ed.:  Robert Berkow Ed.; Merck Research
Laboratories, 1992.  Pp. 305, 315.

HEMATOLOGY, 4th Ed,:  William J. Williams, et al,; Editors; McGraw-Hill,
Inc., 1990.  Pp. 964-969.

BIRTH DEFECTS ENCYCLOPEDIA, Mary Louise Buyse, M.D., Editor-In-Chief;
Blackwell Scientific Publications, 1990.  Pp. 963-64.

NELSON TEXTBOOK OF PEDIATRICS, 14th Ed.; Richard E. Behrman et al; W.B.
Saunders Co., 1992.  Pp. 555, 1280.

IMMUNODEFICIENCY.  Buckley, R.H.  J Allergy Clin Immunol Dec 1983;
72(6):627-641.

WISKOTT-ALDRICH SYNDROME:  NEW MOLECULAR AND BIOCHEMICAL INSIGHTS.  M.
Peacocke; J Am Acad Dermatol (Oct 1992; 27(4)).  Pp. 507-19.

EVIDENCE FOR DEFECTIVE TRANSMEMBRANE SIGNALING IN B CELLS FROM PATIENTS
WITH WISKOTT-ALDRICH SYNDROME.  H.U. Simon; J Clin Invest (Oct 1992; 90(4)).
Pp. 1396-405.

EARLY BONE MARROW TRANSPLANTATION IN AN INFANT WITH WISKOTT-ALDRICH
SYNDROME.  L.J. Beard; Am J Pediatr Hematol Oncol (Fall 1992; 13(3)).  Pp.
310-14.

BONE MARROW TRANSPLANTATION FOR GENETIC DISORDERS.  J.A. Brochstein;
Oncology (March 1992; 6(3)).  Pp. 51-58, 63-66.