Wiskott Aldrich syndrome - Rare Gastroenterology News

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Disease Profile

Wiskott Aldrich syndrome

1-9 / 1 000 000

US Estimated

Europe Estimated

Age of onset

Infancy

ICD-10

D82.0

Inheritance

Wiskott Aldrich syndrome (WAS) is inherited in an X-linked recessive manner. A condition is X-linked if the responsible gene is located on the X chromosome. The X chromosome is one of the two sex chromosomes (the other sex chromosome is the Y chromosome). Females have two X chromosomes in each cell and males have an X chromosome and a Y chromosome in each cell.

Although females have two X chromosomes, one of the X chromosomes in each cell is "turned off" and all of the genes on that chromosome are inactivated. Females who have a mutation in a gene on one of their X chromosomes are called carriers of the related condition. Carrier females usually do not have symptoms of the condition because usually the X chromosome with the mutated gene is turned off. Therefore, they have another X chromosome with a working copy of the gene. Sometimes, the X chromosome with the working copy of the gene is turned off, which may cause symptoms of the condition. However, females with symptoms are usually much more mildly affected than males. A male has only one X chromosome, so if he inherits a mutation on the X chromosome, he will have signs and symptoms (be affected).

Males with an X-linked recessive condition always pass the mutated gene to all of their daughters, who will be carriers. A male cannot pass an X-linked gene to his sons because males always pass their Y chromosome to male offspring.^[6]

Female carriers of an X-linked recessive condition have a 25% chance with each pregnancy to have a carrier daughter like themselves, a 25% chance to have a non-carrier daughter, a 25% chance to have an affected son, and a 25% chance to have an unaffected son.^[6] This also means that each daughter of a carrier mother has a 50% chance of being a carrier, and each son has a 50% chance of having the condition.

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

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.

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.

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

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.

Not applicable

Other names (AKA)

WAS; Eczema thrombocytopenia immunodeficiency syndrome; Immunodeficiency 2;

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 platelets; susceptibility 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

Canadian Immunodeficiencies Patient Organization (CIPO)
25 La Grave St
Winnepeg, MB
R3V 1J1 Canada
Telephone: 877-262-2476 (toll-free)
Fax: 866-942-7651 (toll-free)
E-mail: https://www.cipo.ca/#contact
Website: https://cipo.ca
Immune Deficiencies Foundation Australia
PO Box 969
Penrith NSW 2751
Australia
Telephone: 800-100-198
E-mail: [email protected]
Website: https://www.idfa.org.au/
Jeffrey Modell Foundation (JMF)
780 Third Ave
New York, NY 10017
Fax: 212-764-4180
E-mail: [email protected]
Website: https://www.info4pi.org/
JMF is a global patient organization devoted to early and precise diagnosis, meaningful treatments, and ultimately, cures through clinical and basic research, physician education, patient support, advocacy, public awareness and newborn screening.
Platelet Disorder Support Association
8751 Brecksville Road
Suite 150
Cleveland, OH 44141
Toll-free: 87-PLATELET (1-877-528-3538)
Telephone: 440-746-9003
Fax: 844-270-1277
E-mail: [email protected]
Website: https://www.pdsa.org/
Wiskott-Aldrich Foundation (WAS Community)
4480 South Cobb Drive
Ste H, PMB 223
Smyrna, GA 30080-6989
Telephone: +1-919-641-7134
E-mail: [email protected]
Website: https://www.wiskott.org/

Organizations Providing General Support

Immune Deficiency Foundation
110 West Road, Suite 300
Towson, MD 21204
Toll-free: 1-800-296-4433
Fax: +1-410-321-9165
E-mail: https://www.primaryimmune.org/services/ask-idf/
Website: https://www.primaryimmune.org/
Primary Immune Deficiency UK (PID UK)
PO Box 6970
Basingstoke, RG24 4XL United Kingdom
Toll-free: 0800 987 8986
E-mail: [email protected]
Website: https://www.piduk.org/

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

Filipovich AH, Johnson J & Zhang K. WAS-Related Disorders. GeneReviews. 2016; https://www.ncbi.nlm.nih.gov/books/NBK1178/.
Clinical Diagnostic criteria for PID. European Society for Immunodeficiencies. https://esid.org/Working-Parties/Clinical/Resources/Diagnostic-criteria-for-PID2.
Wiskott-Aldrich syndrome. Genetics Home Reference. February, 2013; https://ghr.nlm.nih.gov/condition/wiskott-aldrich-syndrome.
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.
Schwartz RA. Pediatric Wiskott-Aldrich Syndrome. Medscape Reference. March 3, 2017; https://emedicine.medscape.com/article/888939-overview#a8.
WAS Related Disorders. NORD. February 15, 2008; https://www.rarediseases.org/rare-disease-information/rare-diseases/byID/76/viewAbstract.

Rare Gastroenterology News

Rare Gastroenterology News

Rare Gastroenterology News

Infancy

D82.0

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

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.

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.

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

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.

Not applicable

Other names (AKA)

Categories

Summary

Symptoms

Related diseases

Organizations

Organizations Supporting this Disease

Organizations Providing General Support

Learn more

Where to Start

In-Depth Information

References

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.

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