The syndrome is named after Dr Robert Anderson Aldrich (1917–1998), an American pediatrician who

described the disease in a family of Dutch-Americans in 1954,[1] and Dr Alfred Wiskott (1898–1978), a German
pediatrician who first noticed the syndrome in 1937.[10] Wiskott described three brothers with a similar disease,
whose sisters were unaffected. In 2006 a German research group analysed family members of Wiskott's three cases,
and surmised that they probably shared a novel frameshift mutation of the first exon of the WAS gene.[1

Wiskott-Aldrich syndrome (eczema-thrombocytopenia)Chronic eczema with chronic suppurative otitis media,

anemia, and thrombocytopenic purpura, an immunodeficiency syndrome transmitted as an X-linked recessive trait,
with poor antibody response to polysaccharide antigens and dysfunction of cell-mediated immunity.

Wiskott-Aldrich syndrome is a condition that affects blood cells and cells of the immune system. This condition
is seen almost exclusively in males. Individuals with this condition have microthrombocytopenia, which is a decrease
in the number and size of blood cells involved in clotting (platelets). This platelet abnormality, which is typically
present from birth, can lead to easy bruising or episodes of prolonged bleeding following minor trauma. Eczema, an
inflammatory skin disorder characterized by abnormal patches of red, irritated skin, often occurs in people with this
condition. Affected individuals also have an increased risk of infection due to dysfunction of many types of immune
cells, such as T cells, B cells, dendritic cells, and natural killer cells. Some people develop autoimmune disorders,
which occur when the immune system malfunctions and attacks the body's tissues and organs by mistake. The risk of
developing some types of cancer, such as cancer of the immune system cells (lymphoma), is increased in people with
Wiskott-Aldrich syndrome.

Mutations in the WAS gene cause Wiskott-Aldrich syndrome. The WAS protein (WASP) is found in cells made
from hematopoietic stem cells, including blood cells and certain immune cells. This protein is involved in relaying
signals from the cell surface to the actin cytoskeleton, which is a network of fibers that make up the cell's structural
framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to
move. WAS gene mutations impair WASP's role in cell signaling and disrupt the function of the actin cytoskeleton in
certain immune cells and blood cells. Immune cells that lack WASP function tend to have trouble responding to
factors that trigger cell growth and division (proliferation). Additionally, these defective cells have problems with cell
movement (motility) and difficulty attaching to other cells (cell adhesion). These disruptions in normal immune cell
function contribute to eczema and the increased risk of infection, autoimmune disorders, and lymphoma associated
with this condition. Impaired WASP function also interferes with normal platelet development, causing
microthrombocytopenia, the characteristic sign of Wiskott-Aldrich syndrome.

Mutations in the WAS gene cause Wiskott-Aldrich syndrome. The WAS protein (WASP) is found in cells made
from hematopoietic stem cells, including blood cells and certain immune cells. This protein is involved in relaying
signals from the cell surface to the actin cytoskeleton, which is a network of fibers that make up the cell's structural
framework. The actin cytoskeleton has several critical functions, including determining cell shape and allowing cells to
move. WAS gene mutations impair WASP's role in cell signaling and disrupt the function of the actin cytoskeleton in
certain immune cells and blood cells. Immune cells that lack WASP function tend to have trouble responding to
factors that trigger cell growth and division (proliferation). Additionally, these defective cells have problems with cell
movement (motility) and difficulty attaching to other cells (cell adhesion). These disruptions in normal immune cell
function contribute to eczema and the increased risk of infection, autoimmune disorders, and lymphoma associated
with this condition. Impaired WASP function also interferes with normal platelet development, causing
microthrombocytopenia, the characteristic sign of Wiskott-Aldrich syndrome.
 How do people inherit Wiskott-Aldrich syndrome?

This condition is inherited in an X-linked recessive pattern. The gene associated with this condition is located on
the X chromosome, which is one of the two sex chromosomes. In males (who have only one X chromosome), one
altered copy of the gene in each cell is sufficient to cause the condition. In females (who have two X chromosomes), a
mutation would have to occur in both copies of the gene to cause the disorder. Because it is unlikely that females will
have two altered copies of this gene, males are affected by X-linked recessive disorders much more frequently than
females. A striking characteristic of X-linked inheritance is that fathers cannot pass X-linked traits to their sons.

Pattern of inheritance
The gene for Wiskott-Aldrich syndrome is found on the X chromosome. Because females have two X chromosomes, if
they have a mutation on one X chromosome, they have a spare X that can help compensate for the mutation. Males
have one X chromosome and one Y chromosome. Since they do not have a spare X chromosome, they show signs of a
mutation inherited on the X chromosome. Although, a female who carries a mutation for Wiskott-Aldrich
syndrome on one of her X chromosomes, shows no sign of immunodeficiency, her sons and daughters have a 50
percent chance of inheriting the X chromosome with the mutation (and a 50 percent chance of inheriting the normal
X chromosome).  The sons who inherit the mutant X chromosome will have WAS and the daughters who inherit the
mutant X chromosome will be carriers like their mother. Carriers of WAS can be identified by mutation detection (a
laboratory test).

All of the daughters of a man with Wiskott-Aldrich syndrome will be carriers of WAS; but the sons, who have
inherited his unaffected Y chromosome, will be normal. About 50 percent of patients with Wiskott-Aldrich
syndrome will have a brother, cousin or uncle with WAS.  In most remaining families, the affected individual
represents the first sign of a new mutation (mistake) in the WAS gene in his family.  We do not know what causes
new mutations in most families. Typically, the disorder affects males, but there have been some females who appear
to have the same physical problems as males with WAS, without the genetic mutation (mistake).

Clinical Features and Symptoms

The diagnosis of Wiskott-Aldrich syndrome is suspected in males who have bleeding in the newborn period.
This is most often manifested as bloody diarrhea. Other patients are recognized to have WAS when a blood count
(CBC) that is done during an infection, shows a low platelet count with small platelets. Because of the defect in T cells
and B cells, patients with WAS are at increased risk for both bacterial and viral infections. Otitis (ear infections),
sinusitis and pneumonia are frequently seen in patients with Wiskott-Aldrich syndrome. Viral infections caused by
herpes simplex and EBV (Epstein-Barr Virus) can also be troublesome.

Autoimmune disorders, caused by an abnormal immune system, can also be observed in males with WAS.
These include vasculitis, arthritis, and autoimmune hemolytic anemia.An increased incidence of malignancy has also
been observed in patients with WAS. Specifically, EBV-related brain tumors, leukemias and lymphomas are seen.

Medical Treatment
Antibiotics are indicated to treat bacterial infections and for prophylaxis in patients who have had a
splenectomy. Antiviral and antifungal agents are indicated to treat viral and fungal infections, respectively.
Chemotherapeutic agents are indicated to treat lymphoreticular and/or hematologic malignancies, but are also used
as ablative agents, with or without total-body irradiation, prior to bone marrow transplantation. Immunoglobulins
and systemic corticosteroids are indicated to treat thrombocytopenia. Use topical steroids to treat eczema. Aspirin
and other non-steroidal anti-inflammatory drugs should be avoided, since these may interfere with platelet function.
 Surgical Tx: splenectomy (bleeding) and Bone marrow transplantation may be curative if an appropriate
histocompatible donor is available.

Laboratory Diagnostic
Quantitative serum immunoglobulin levels

 Measure quantitative serum immunoglobulin levels of all other classes (ie, immunoglobulin A [IgA],
immunoglobulin G [IgG], immunoglobulin E [IgE]).
 This measurement assists with accurate diagnosis because IgM deficiency may be part of a more extensive
humoral immunodeficiency (eg, common variable immunodeficiency).
 In classic WAS, IgM levels are low and IgG levels are relatively normal, but IgA and IgE levels may be elevated.
On the other hand, in common variable immunodeficiency, a low IgG level is the hallmark of the disease,
which is associated with low IgA levels, low IgM levels, or both.

Functional testing of the humoral and cellular components of the immune system

 Test humoral immune function by measuring the patient's ability to develop antibody responses to standard
polysaccharide and protein antigen vaccines (eg, pneumococcal vaccine, tetanus toxoid), using
preimmunization and postimmunization antibody titers.
 Measure cellular immune function by examining lymphocyte proliferative responses to mitogens, alloantigen,
and recall antigens and the patient's ability to react to anergy battery skin testing with delayed-type (type IV)
hypersensitivity responses. The latter skin test antigens typically consist of candidal, mumps, trichophyton,
and tetanus toxoid antigens.
 In WAS, defects in a patient's response to polysaccharide vaccination and anergy are common. Responses to
protein antigens and lymphocyte proliferation may also be impaired.2

Complete blood cell count

 Obtain a complete blood cell count with manual differential, lymphocyte enumeration, and peripheral blood
smear. Enumeration of T- and B-cell subsets by flow cytometry may be helpful.
 This test provides quantitative and morphologic information about cellular elements of the immune system
and information about platelet numbers and morphology.

Procedures

 Consider obtaining a bone marrow biopsy to assist diagnosis in complex cases or to evaluate for hematologic
malignancy. However, patients generally do not require bone marrow biopsy. If performed, megakaryocytes
usually appear normal.32
 If meningitis is considered, a lumbar puncture may be necessary.
 Recurrent otitis media may require tympanostomy tube placement.