Diseases » Wiskott-Aldrich Syndrome

Wiskott Aldrich Syndrome

Wiskott Aldrich Syndrome: Excerpt from The 5-Minute Pediatric Consult

Elena Elizabeth Perez, MD, PhD

Wiskott Aldrich Syndrome - BASICS

Wiskott Aldrich Syndrome - description

• An X-linked primary immunodeficiency characterized by the classic clinical triad of thrombocytopenia with small platelets, eczema, and recurrent infections with opportunistic and pyogenic organisms.
• Also associated with IgA nephropathy, autoimmune disorders, and an increased incidence of B-cell lymphomas
• Milder disease variant is known as X linked thrombocytopenia or XLT

Wiskott Aldrich Syndrome - epidemiology

• Presents in infancy with serious bleeding episodes secondary to thrombocytopenia (such as circumcision with increased bleeding, bloody diarrhea, ecchymoses)
• Recurrent infections usually start after 6 months of age:
  • Bacterial: Otitis media, sinusitis, meningitis, sepsis, and pneumonia
  • Viral infections: Herpes simplex virus, varicella with systemic complications
• Milder phenotypes may lack history of recurrent infections.
• Eczema is usually present by 1 year of age. (May be resistant to therapy, sometimes requiring systemic antibiotics)

Wiskott Aldrich Syndrome - incidence

• For WAS/XLT estimate is 10 in 1 million live births.
• Prevalence of XLT equal to WAS.

Wiskott Aldrich Syndrome - risk-factors

Wiskott Aldrich Syndrome - genetics

• X-linked recessive disease
• Defective Wiskott-Aldrich syndrome protein gene located on X p11.22p–11.23.
• ~60% of cases will have a positive family history for Wiskott-Aldrich syndrome.
• X-linked thrombocytopenia without the other findings is caused by mutations of the same gene.
• Genotype/Phenotype correlation:
  • Lack of WASP expression—increased infections, severe eczema, intestinal hemorrhage, death from intracranial bleeding, and malignancies.
  • Survival rate significantly lower in WASP-negative patients.

Wiskott Aldrich Syndrome - etiology

• Mutations in the gene for the Wiskott–Aldrich syndrome protein (WAS).
• WAS protein (WASP) is involved in the reorganization of the actin cytoskeleton in hematopoietic cells.
  • Following activation of WASP, reorganization of actin cytoskeleton results in polarization of cells (e.g., polarized actin mesh in platelets for clotting, in macrophages for phagocytosis, and polarization of T or B cells to form immunologic synapses).

Wiskott Aldrich Syndrome - DIAGNOSIS

Wiskott Aldrich Syndrome - signs & symptoms

Wiskott Aldrich Syndrome - history

• Persistent or severe bleeding in infancy due to thrombocytopenia
• Recurrent infections, especially by bacteria with capsular polysaccharides (e.g., Pneumococcus)
• Eczema can be of variable severity.
• Older patients may report recurrent viral infections.
• Maternal family history of Wiskott-Aldrich syndrome or X-linked thrombocytopenia

Wiskott Aldrich Syndrome - physical exam

• Evaluation should focus on presence of infection.
• Dermatologic examination is significant for the extent of eczema and the presence of petechiae or ecchymoses.
• Splenomegaly

Wiskott Aldrich Syndrome - tests

Wiskott Aldrich Syndrome - lab

• CBC with differential
• Small platelets, decreased mean platelet volume. Decreased platelet count
• Normal IgG, decreased IgM, and increased IgA and IgE
• Reduced or absent responses to polysaccharide antigens and isohemagglutinins to ABO antigens.
• T- and B-lymphocyte enumeration and mitogen stimulation studies may progressively deteriorate with increasing age.

Wiskott Aldrich Syndrome - diag-proced-surgery

• Sequencing of WAS gene
• Lymph node biopsy in suspected malignancy
• Bone marrow aspirate to evaluate thrombocytopenia

Wiskott Aldrich Syndrome - differencial diagnosis

• Other causes of thrombocytopenia such as idiopathic thrombocytopenic purpura
• Severe atopic disease with dermatitis and secondary skin infections
• HIV infection
• Hyper-IgE syndrome
• Diagnosis should be considered in any boy who has congenital or early-onset thrombocytopenia with small platelets.
• Definitive diagnosis:
  • Male patient
  • Congenital thrombocytopenia (<70,000/mm³)
  • Small platelets (mean platelet volume <0.5 fL)
  • Mutation in the Wiskott-Aldrich syndrome protein gene or absent Wiskott-Aldrich syndrome protein mRNA

Wiskott Aldrich Syndrome - TREATMENT

Wiskott Aldrich Syndrome - general measures

• Antibiotics for acute infections and prophylactically in postsplenectomy patients
• Splenectomy may be helpful for persistent severe thrombocytopenia in select patients. However, this may greatly increase the risk of overwhelming infections with encapsulated organisms.
• Thrombocytopenia precautions: No aspirin and avoidance of situations in which trauma (especially head trauma) is likely to occur, such as contact sports
• Platelet transfusions may be necessary for severe bleeding. Use irradiated blood products to avoid graft versus host disease, and cytomegalovirus-negative products in case of bone marrow transplantation.
• IV immunoglobulin replacement therapy is helpful in managing recurrent infections in some patients.
• Bone marrow transplantation should be considered if a full match is available:
  • Overall success rate of HLA-identical bone marrow transplantation is 85%.
  • Use of haploidentical bone marrow transplantation is controversial because of a lower success rate.
  • Cord blood as a source of stem cells is also a curative therapy.
• Consider food allergy as exacerbating factor for eczema.
• Gene therapy under development

Wiskott Aldrich Syndrome - FOLLOW UP

Wiskott Aldrich Syndrome - complications

• Progressive decline in immunologic function with an increase in infections. Humoral and cellular immune systems are affected.
• Increased frequency of autoimmune phenomena such as arthritis and vasculitis. The most common is hemolytic anemia. Vasculitis, Henoch-Schönlein purpura, inflammatory polyarthritis, and inflammatory bowel disease are also observed.
• ~100-fold increased risk of malignancy compared with the general pediatric population. Malignancy is more common in adolescents. Associated with Epstein-Barr virus
• Bleeding episodes can be life threatening.

Wiskott Aldrich Syndrome - patient-monitoring

• Signs and symptoms of malignancy should be evaluated expeditiously.
• As patients age, a progressive increase in infectious and autoimmune complications may occur.

Wiskott Aldrich Syndrome - bibliography

1. Binder V, Albert M, Kabus M, et al. The genotype of the original Wiskott phenotype. N Engl J Med. 2006: 355:1790–1793.
2. Charrier S, Dupre L, Scaramuzza S, et al. Lentiviral vectors targeting WASP expression tohematopoietic cells, efficiently transduce and correct cells from WAS patients. Gene Therapy. 2006;1–14.
3. Derry JMD, Ochs HD, Francke U. Isolation of novel gene mutated in Wiskott-Aldrich syndrome. Cell. 1994;78:635–644.
4. Imai K, Morio T, Zhu Y, et al. Clinical course of patients with WASP gene mutations. Blood. 2004:103(2):456–464.
5. Jin Y, Mazza C, Christie J, et al. Mutations of the Wiskott-Aldrich syndrome protein (WASP): Hotspots, effect on transcription, and translation and phenotype/genotype correlation. Blood. 2004;104(13):4010–4019.
6. Litzman J, Jones A, Hann I, et al. Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome. Arch Dis Child. 1996;75:43–69.
7. Lutskiy M, Rosen F, O’Donnell E. Genotype-proteotype linkage in the Wiskott-Aldrich syndrome. J Immunol. 2005;175:129–133.
8. Nonoyama S, Ochs HD. Wiskott-Aldrich syndrome. Curr Allergy Asthma Rep. 2001;1:430–437.
9. Ochs HD. The Wiskott-Aldrich syndrome. Clin Rev Allergy Immunol. 2001;20:61–86.
10. Ochs HD, Slichter SJ, Harker LA, et al. The Wiskott-Aldrich syndrome: Studies of lymphocytes, granulocytes, and platelets. Blood. 1980;55:243–252.
11. Puck J, Candotti F. Lessons from the Wiskott-Aldrich Syndrome. NEJM. 2006:355;17:159–176.
12. Schurman SH, Candotti F. Autoimmunity in Wiskott-Aldrich syndrome. Curr Opin Rheum. 2003;15:446–453.
13. Shcherbina A, Candotti F, Rosen F, et al. High incidence of lymphomas in subgroups of Wiskott-Aldrich syndrome patients. Br J Haematol. 2003;121:529.
14. Snapper SB, Rosen FS. A family of WASPs. N Engl J Med. 2003;348:350–351.
Stites DP, Terr AI. Basic and Clinical Immunology. 7th ed. Norwalk, CT: Appleton-Lange; 1991:346–347.
15. Sullivan KS, Mullen CA, Blaise RM, et al. A multi-institutional survey of Wiskott-Aldrich syndrome. J Pediatr. 1994;125:876–885.
16. Thrasher A. WASp in immune-system organization and function. Nat Rev Immunol. 2002;2:635–646.
Winkelstein JA, et al., eds. Patient and Family Handbook: For the Primary Immune Deficiency Diseases. 2nd ed. Immune Deficiency Foundation; 1993.

Wiskott Aldrich Syndrome - CODES

Wiskott Aldrich Syndrome - icd9

279.12 Wiskott-Aldrich syndrome

Wiskott Aldrich Syndrome - FAQ

• Q: What is the life expectancy for Wiskott-Aldrich syndrome patients?
• A: Before currently available therapies, most affected patients died in childhood. Currently, many patients live into their third and fourth decades, even without bone marrow transplantation. Major causes of mortality are infections (44%), bleeding (23%), and malignancies (26%). Incidence of malignancy increases in third decade of life. Successfully transplanted patients have a prolonged life expectancy. Patients with no gene expression have a poorer outcome.
• Q: Should patients with Wiskott-Aldrich syndrome receive live viral vaccines?
• A: These vaccines should be avoided because of the variable cellular immune defects associated with Wiskott-Aldrich syndrome. Any patients receiving IV immunoglobulin do not require vaccinations.
• Q: What is the chance of a sibling having Wiskott-Aldrich syndrome?
• A: As with any X-linked disease, there is a 50% chance of another affected male child or asymptomatic carrier female. Genetic counseling should be offered to carrier females.
• Q: Can Wiskott-Aldrich syndrome be diagnosed prenatally?
• A: In families with affected males, fetal blood sampling can be performed in male fetuses to assess the size of the platelets. Small platelet size and family history of Wiskott-Aldrich syndrome suggests an affected infant.

>>

Book Source Details

• Book Title: The 5-Minute Pediatric Consult
• Author(s): M. William Schwartz MD; et al.
• Year of Publication: 2008
• Copyright Details: The 5-Minute Pediatric Consult, Copyright © 2008 Lippincott Williams & Wilkins.

More About Wiskott-Aldrich Syndrome

• Back to disease: Wiskott-Aldrich Syndrome: Introduction
• Next Book Extract About Wiskott-Aldrich Syndrome: Surveys relating to Wiskott-Aldrich Syndrome
• More Book Extracts: All Online Books for Wiskott-Aldrich Syndrome

More Medical Textbooks Online about Wiskott-Aldrich Syndrome

Review other book chapters online related to Wiskott-Aldrich Syndrome:

Copyright notice for book excerpts: Copyright © 2008 Lippincott Williams & Wilkins. All rights reserved.

---

More About This Book: Title: The 5-Minute Pediatric Consult Authors: M. William Schwartz MD; et al. Publisher: Lippincott Williams & Wilkins Copyright: 2008 ISBN: 0-7817-7577-9

 » Next page: Surveys relating to Wiskott-Aldrich Syndrome

Rate This Website

What do you think about the features of this website? Take our user survey and have your say:

Website User Survey

Medical Tools & Articles:

Next articles:

• Surveys relating to Wiskott-Aldrich Syndrome
• Ask Question about Wiskott-Aldrich Syndrome

Tools & Services:

• Bookmark this page
• Symptom Search
• Symptom Checker
• Medical Dictionary
• Give your feedback

Medical Articles:

• Disease & Treatments Search
• Misdiagnosis Center
• Full list of interesting articles

Forums & Message Boards

• Ask or answer a question at the Boards:
• I cannot get a diagnosis. Please help.
• Tell us your medical story.
• Share your misdiagnosis story.
• What is the best treatment for my condition?
• See all the Boards.

homepage | back to top

Common Health Mistakes

Choose ... Alzheimers & Dementia Asthma Child ADHD ADHD in Adults Allergy Hypertension Bipolar Breast Cancer Celiac Disease Crohns Disease Colon Cancer Contraception Diabetes Cancer Depression Erectile Disorder Cholesterol COPD GERD Heartburn/Reflux Metabolic Syndrome Migraine/Headache Multiple Sclerosis Obesity Osteoporosis Overactive Bladder Psoriasis Sexual Disorder Sleep Disorders Smoking The Pill Ulcerative Colitis All Common Mistakes

Symptom
Checker

Choose... Fever Rash Pain Headache Fatigue Cough Other symptoms

Search Specialists by State and City

Choose... GENERAL PRACTICE CARDIAC HEALTH WOMEN'S HEALTH CANCER CARE RADIOLOGY MENTAL HEALTH PATHOLOGY EAR, NOSE, THROAT MEDICINE GENETICS NEUROLOGY DIALYSIS CARE SURGERY ORTHOPEDICS/SPORTS MEDICINE CHILDREN'S HEALTH OTHER SPECIALTIES