Rare Gastroenterology News

Disease Profile

Wiskott Aldrich syndrome

Prevalence
Prevalence estimates on Rare Medical Network websites are calculated based on data available from numerous sources, including US and European government statistics, the NIH, Orphanet, and published epidemiologic studies. Rare disease population data is recognized to be highly variable, and based on a wide variety of source data and methodologies, so the prevalence data on this site should be assumed to be estimated and cannot be considered to be absolutely correct.
1-9 / 1 000 000

331 - 2,979

US Estimated

1-9 / 1 000 000

514 - 4,622

Europe Estimated

Age of onset

Infancy

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ICD-10

D82.0

Inheritance

Autosomal dominant A pathogenic variant in only one gene copy in each cell is sufficient to cause an autosomal dominant disease

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Autosomal recessive Pathogenic variants in both copies of each gene of the chromosome are needed to cause an autosomal recessive disease and observe the mutant phenotype

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X-linked
dominant X-linked dominant inheritance, sometimes referred to as X-linked dominance, is a mode of genetic inheritance by which a dominant gene is carried on the X chromosome.

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X-linked
recessive Pathogenic variants in both copies of a gene on the X chromosome cause an X-linked recessive disorder

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Mitochondrial or multigenic Mitochondrial genetic disorders can be caused by changes (mutations) in either the mitochondrial DNA or nuclear DNA that lead to dysfunction of the mitochondria and inadequate production of energy.

Multigenic or multifactor Inheritance involving many factors, of which at least one is genetic but none is of overwhelming importance, as in the causation of a disease by multiple genetic and environmental factors.

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Not applicable

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Other names (AKA)

WAS; Eczema thrombocytopenia immunodeficiency syndrome; Immunodeficiency 2;

Categories

Blood Diseases; Congenital and Genetic Diseases; Immune System Diseases;

Summary

Wiskott Aldrich syndrome (WAS) is a disease with immunological deficiency and reduced ability to form blood clots. Signs and symptoms include easy bruising or bleeding due to a decrease in the number and size of plateletssusceptibility to infections and to immune and inflammatory disorders; and an increased risk for some cancers (such as lymphoma). Also, a skin condition known as eczema is common in people with WAS.[1][2] Wiskott Aldrich syndrome is caused by mutations in the WAS gene and is inherited in an X-linked manner.[3] It primarily affects males. Treatment may depend on severity and symptoms in each person, but hematopoietic cell transplantation is the only known cure.[1] Hematopoietic cells are the blood-forming stem cells that can be found mainly in the sponge-like material found inside bones (bone marrow), but also in the bloodstream (peripheral blood stem cells (PBSCs), and in the umbilical cord.[4] Prognosis have improved over time due to better management of the disease. People who have a successful and uncomplicated hematopoeitic cell transplantation, usually have normal immune function and, normal survival.[5]

Wiskott-Aldrich syndrome, X-linked thrombocytopenia (XLT), and X-linked neutropenia (XLN) are known as “WAS-related disorders” because these diseases are all caused by mutations in the WAS gene, and have overlapping symptoms ranging from severe to mild (Wiskott-Aldrich syndrome is the most severe). The WAS gene mutations result in deficiency of the Wiskott-Aldrich syndrome protein (WASP). The more deficient the WASP, the more severe the disease.[1]

Symptoms

Common signs and symptoms of Wiskott-Aldrich syndrome include the following.

  • Decreased numbers of platelets (thrombocytopenia), and very small platelets usually present at birth which can result in:
    • Bleeding inside the brain, which can be very fatal
    • Mucosal (such as insed the mouth) bleeding
    • Bloody diarrhea
    • Bruising or purplish areas on the skin or mucous membranes (purpura), caused by bleeding under the skin
    • Pinpoint red spots on the skin (petechiae).
    • Life-threatening bleeding (occurs in 30% of males prior to diagnosis)
  • Red patches of red and irritated skin (eczema), ccurs in about 80% of the cases and can be mild to severe
  • Other skin diseases such as impetigo, cellulitis, and abscesses
  • Increased risk of infections, especially to recurrent bacterial and viral infections, mostly recurrent ear infections and some viruses such as cytomegalovirus (CMV), herpes simplex virus (HSV), Epstein-Barr virus (EBV).
  • Increased risk of developing autoimmune disorders (when the immune system mistakenly attacks the body's own tissues and organs) specially when people get older, and that may include hemolytic anemia (destruction of red blood cells), immune thrombocytopenic purpura, rheumatoid arthritis, vasculitis of small and large vessels, and immune-mediated damage to the kidneys and liver
  • Increased risk of developing some types of cancer, such as lymphoma, especially in people with WAS who had an EBV infection or are older and have an autoimmune disease

This table lists symptoms that people with this disease may have. For most diseases, symptoms will vary from person to person. People with the same disease may not have all the symptoms listed. This information comes from a database called the Human Phenotype Ontology (HPO) . The HPO collects information on symptoms that have been described in medical resources. The HPO is updated regularly. Use the HPO ID to access more in-depth information about a symptom.

Medical Terms Other Names
Learn More:
HPO ID
80%-99% of people have these symptoms
Abnormal platelet morphology
Abnormal shape of platelets
0011875
Bruising susceptibility
Bruise easily
Easy bruisability
Easy bruising

[ more ]

0000978
Chronic diarrhea
0002028
Chronic otitis media
Chronic infections of the middle ear
0000389
Chronic pulmonary obstruction
0006510
Fever
0001945
Immunodeficiency
Decreased immune function
0002721
Lymphopenia
Decreased blood lymphocyte number
Low lymphocyte number

[ more ]

0001888
Prolonged bleeding time
0003010
Recurrent respiratory infections
Frequent respiratory infections
Multiple respiratory infections
respiratory infections, recurrent
Susceptibility to respiratory infections

[ more ]

0002205
Sinusitis
Sinus inflammation
0000246
Spontaneous hematomas
0007420
Thrombocytopenia
Low platelet count
0001873
30%-79% of people have these symptoms
Abnormal eosinophil morphology
0001879
Autoimmunity
Autoimmune disease
Autoimmune disorder

[ more ]

0002960
Dyspnea
Trouble breathing
0002094
Fatigue
Tired
Tiredness

[ more ]

0012378
Hematemesis
Vomitting blood
0002248
Hematochezia
Rectal bleeding
0002573
Hemolytic anemia
0001878
Inflammation of the large intestine
0002037
Microcytic anemia
0001935
Petechiae
0000967
Specific learning disability
0001328
5%-29% of people have these symptoms
Abnormal platelet function
0011869
Abnormality of the menstrual cycle
0000140
Acute leukemia
0002488
Arthritis
Joint inflammation
0001369
Blepharitis
Inflammation of eyelids
0000498
Chest pain
0100749
Chronic leukemia
0005558
Conjunctivitis
Pink eye
0000509
Eczema
0000964
Epistaxis
Bloody nose
Frequent nosebleeds
Nose bleed
Nose bleeding
Nosebleed

[ more ]

0000421
Gingival bleeding
Bleeding gums
0000225
Glomerulopathy
0100820
Hyperostosis
Bone overgrowth
0100774
Hypoplasia of the thymus
Small thymus
0000778
Intracranial hemorrhage
Bleeding within the skull
0002170
Keratitis
Corneal inflammation
0000491
Lymphoma
Cancer of lymphatic system
0002665
Meningitis
0001287
Nephropathy
0000112
Neutropenia
Low blood neutrophil count
Low neutrophil count

[ more ]

0001875
Peripheral neuropathy
0009830
Recurrent intrapulmonary hemorrhage
Recurrent bleeding into lungs
0006535
Sepsis
Infection in blood stream
0100806
Skin ulcer
Open skin sore
0200042
Sudden cardiac death
Premature sudden cardiac death
0001645
Urticaria
Hives
0001025
Vasculitis
Inflammation of blood vessel
0002633
Percent of people who have these symptoms is not available through HPO
Abnormal delayed hypersensitivity skin test
0002963
Absent microvilli on the surface of peripheral blood lymphocytes
0002971
Decreased circulating total IgM
0002850
Decreased mean platelet volume
Small platelet size
Small platelets
Small platelets size

[ more ]

0005537
Decreased specific anti-polysaccharide antibody level
0002848
Increased circulating IgA level
0003261
Increased circulating IgE level

Related diseases

Related diseases are conditions that have similar signs and symptoms. A health care provider may consider these conditions in the table below when making a diagnosis. Please note that the table may not include all the possible conditions related to this disease.

Conditions with similar signs and symptoms from Orphanet
Main differential diagnosis is acute or chronic idiopathic thrombocytopenia (ITP) or platelet alloimmunization in neonates.
Visit the Orphanet disease page for more information.

Organizations

Support and advocacy groups can help you connect with other patients and families, and they can provide valuable services. Many develop patient-centered information and are the driving force behind research for better treatments and possible cures. They can direct you to research, resources, and services. Many organizations also have experts who serve as medical advisors or provide lists of doctors/clinics. Visit the group’s website or contact them to learn about the services they offer. Inclusion on this list is not an endorsement by GARD.

Organizations Supporting this Disease

    Organizations Providing General Support

      Learn more

      These resources provide more information about this condition or associated symptoms. The in-depth resources contain medical and scientific language that may be hard to understand. You may want to review these resources with a medical professional.

      Where to Start

      • Genetics Home Reference (GHR) contains information on Wiskott Aldrich syndrome. This website is maintained by the National Library of Medicine.
      • The Merck Manual provides information on this condition for patients and caregivers.
      • The National Organization for Rare Disorders (NORD) has a report for patients and families about this condition. NORD is a patient advocacy organization for individuals with rare diseases and the organizations that serve them.

        In-Depth Information

        • GeneReviews provides current, expert-authored, peer-reviewed, full-text articles describing the application of genetic testing to the diagnosis, management, and genetic counseling of patients with specific inherited conditions.
        • Medscape Reference provides information on this topic. You may need to register to view the medical textbook, but registration is free.
        • The Monarch Initiative brings together data about this condition from humans and other species to help physicians and biomedical researchers. Monarch’s tools are designed to make it easier to compare the signs and symptoms (phenotypes) of different diseases and discover common features. This initiative is a collaboration between several academic institutions across the world and is funded by the National Institutes of Health. Visit the website to explore the biology of this condition.
        • Online Mendelian Inheritance in Man (OMIM) is a catalog of human genes and genetic disorders. Each entry has a summary of related medical articles. It is meant for health care professionals and researchers. OMIM is maintained by Johns Hopkins University School of Medicine. 
        • Orphanet is a European reference portal for information on rare diseases and orphan drugs. Access to this database is free of charge.
        • PubMed is a searchable database of medical literature and lists journal articles that discuss Wiskott Aldrich syndrome. Click on the link to view a sample search on this topic.

          References

          1. Filipovich AH, Johnson J & Zhang K. WAS-Related Disorders. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK1178/.
          2. Clinical Diagnostic criteria for PID. European Society for Immunodeficiencies. https://esid.org/Working-Parties/Clinical/Resources/Diagnostic-criteria-for-PID2.
          3. Wiskott-Aldrich syndrome. Genetics Home Reference. February, 2013; https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome.
          4. Blood-Forming Stem Cell Transplants. National Cancer Institute. 2013; https://www.cancer.gov/about-cancer/treatment/types/stem-cell-transplant/stem-cell-fact-sheet#q1.
          5. Schwartz RA. Pediatric Wiskott-Aldrich Syndrome. Medscape Reference. March 3, 2017; https://emedicine.medscape.com/article/888939-overview#a8.
          6. WAS Related Disorders. NORD. February 15, 2008; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/76/viewAbstract.

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