Wiskott-Aldrich syndrome

Jump to: navigation, search

WikiDoc Resources for Wiskott-Aldrich syndrome

Articles

Most recent articles on Wiskott-Aldrich syndrome

Most cited articles on Wiskott-Aldrich syndrome

Review articles on Wiskott-Aldrich syndrome

Articles on Wiskott-Aldrich syndrome in N Eng J Med, Lancet, BMJ

Media

Powerpoint slides on Wiskott-Aldrich syndrome

Images of Wiskott-Aldrich syndrome

Photos of Wiskott-Aldrich syndrome

Podcasts & MP3s on Wiskott-Aldrich syndrome

Videos on Wiskott-Aldrich syndrome

Evidence Based Medicine

Cochrane Collaboration on Wiskott-Aldrich syndrome

Bandolier on Wiskott-Aldrich syndrome

TRIP on Wiskott-Aldrich syndrome

Clinical Trials

Ongoing Trials on Wiskott-Aldrich syndrome at Clinical Trials.gov

Trial results on Wiskott-Aldrich syndrome

Clinical Trials on Wiskott-Aldrich syndrome at Google

Guidelines / Policies / Govt

US National Guidelines Clearinghouse on Wiskott-Aldrich syndrome

NICE Guidance on Wiskott-Aldrich syndrome

NHS PRODIGY Guidance

FDA on Wiskott-Aldrich syndrome

CDC on Wiskott-Aldrich syndrome

Books

Books on Wiskott-Aldrich syndrome

News

Wiskott-Aldrich syndrome in the news

Be alerted to news on Wiskott-Aldrich syndrome

News trends on Wiskott-Aldrich syndrome

Commentary

Blogs on Wiskott-Aldrich syndrome

Definitions

Definitions of Wiskott-Aldrich syndrome

Patient Resources / Community

Patient resources on Wiskott-Aldrich syndrome

Discussion groups on Wiskott-Aldrich syndrome

Patient Handouts on Wiskott-Aldrich syndrome

Directions to Hospitals Treating Wiskott-Aldrich syndrome

Risk calculators and risk factors for Wiskott-Aldrich syndrome

Healthcare Provider Resources

Symptoms of Wiskott-Aldrich syndrome

Causes & Risk Factors for Wiskott-Aldrich syndrome

Diagnostic studies for Wiskott-Aldrich syndrome

Treatment of Wiskott-Aldrich syndrome

Continuing Medical Education (CME)

CME Programs on Wiskott-Aldrich syndrome

International

Wiskott-Aldrich syndrome en Espanol

Wiskott-Aldrich syndrome en Francais

Business

Wiskott-Aldrich syndrome in the Marketplace

Patents on Wiskott-Aldrich syndrome

Experimental / Informatics

List of terms related to Wiskott-Aldrich syndrome

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]; Syed Hassan A. Kazmi BSc, MD [3]; Cafer Zorkun, M.D., Ph.D. [4]

Synonyms and Keywords: Aldrich syndrome

Overview

Wiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by eczema, thrombocytopenia (low platelet counts), immune deficiency, and bloody diarrhea (due to the low platelet counts). It is also sometimes called the eczema-thrombocytopenia-immunodeficiency syndrome in keeping with Aldrich's original description in 1954.[1] The WAS-related disorders of X-linked thrombocytopenia (XLT) and X-linked congenital neutropenia (XLN) may present similar but less severe symptoms and are caused by mutations of the same gene.

Historical Perspective

The syndrome is named after Dr Robert Anderson Aldrich, an American pediatrician who described the disease in a family of Dutch-Americans in 1954, and Dr Alfred Wiskott, a German pediatrician who first noticed the syndrome in 1937.[2] 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.[3]

Classification

Jin et al (2004) employ a numerical grading of severity:[4]

Pathophysiology

In the Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.

Wiskott–Aldrich syndrome was linked in 1994 to mutations in a gene on the short arm of the X chromosome, which was termed Wiskott-Aldrich syndrome protein (WASp). It was later discovered that the disease X-linked thrombocytopenia (XLT) was also due to WASp mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked neutropenia has been linked to particular mutations of the WASp gene.

The WASp gene codes for the protein by the same name, which is 502 amino acids long and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the Arp2/3 complex. In T-cell, WASp is important because it is known to be activated via T-cell receptor (TCR) signaling pathways to induce cortical actin cytoskeleton rearrangements that are responsible for forming the immunological synapse.

The immune deficiency is caused by decreased antibody production, and an inability for T cells to become polarized [5] (making it a combined immunodeficiency). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T cells are unable to reorganize their actin cytoskeleton. The type of mutation to the WASp gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a missense mutation but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.

A defect in CD43 molecule has been found to be associated in patients with Wiskott–Aldrich syndrome.[6]

Causes

In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.

Wiskott–Aldrich syndrome was linked in 1994 to mutations in a gene on the short arm of the X chromosome, which was termed Wiskott-Aldrich syndrome protein (WASp). It was later discovered that the disease X-linked thrombocytopenia (XLT) was also due to WASp mutations, but different ones from those that cause full-blown Wiskott–Aldrich syndrome. Furthermore, the rare disorder X-linked neutropenia has been linked to particular mutations of the WASp gene.

The WASp gene codes for the protein by the same name, which is 502 amino acids long and is mainly expressed in hematopoietic cells (the cells in the bone marrow that develop into blood cells). The main function of WASp is to activate actin polymerization by binding to the Arp2/3 complex. In T-cell, WASp is important because it is known to be activated via T-cell receptor (TCR) signaling pathways to induce cortical actin cytoskeleton rearrangements that are responsible for forming the immunological synapse.

The immune deficiency is caused by decreased antibody production, and an inability for T cells to become polarized [5] (making it a combined immunodeficiency). This leads to increased susceptibility to infections, particularly of the ears and sinuses. T-cells are unable to reorganize their actin cytoskeleton. The type of mutation to the WASp gene correlates significantly with the degree of severity: those that led to the production of a truncated protein caused significantly more symptoms than those with a missense mutation but a normal-length WASp. Although autoimmune disease and malignancy occur in both types of mutation, those patients with truncated WASp carry a higher risk.

A defect in CD43 molecule has been found to be associated in patients with Wiskott–Aldrich syndrome.[6]

Differentiating Wiskott-Aldrich Syndrome From Other Disorders of Humoral Imuunodeficiency

Wiskott-Aldrich Syndrome should be differentiated from other disorders leading to hypogammaglobulinemia and defects of humoral immunity. The following conditions may be considered as differentials:[7][8][9][10][11][12][13][14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33][34][30][35][36][37][38][39][40][41][42][43][44][45][46][47][48][49][50][51][52][53][54][55][56]

Disorder Mechanism Characteristic Features Clinical Presentation Laboratory Findings
Wiskott-Aldrich Syndrome
X-Linked (Bruton) Agammaglobulinemia
Selective IgA Deficiency
  • Serum IgA < 7 mg/dl
  • Normal IgG and IgM levels
Common Variable Immunodeficiency
  • Defective B cell differentiation
  • May be acquired in 20-30 years of age
Autosomal dominant hype IgE syndrome (Job's Syndrome)
  • Distinctive coarse facies
  • Cold (non-inflammatory) Staphylococcal abscesses
  • Retained primary teeth
  • Eczema
Severe combined immunodeficiency (SCID)
Ataxia Telangiectasia
Hyper IgM Syndrome
  • Malignancy: can cause the reduction in the immunoglobulin production.
  • Viral infections: such as Epstein-Barr virus, HIV, cytomegalovirus are other causes of hypogammaglobulinemia..
  • Side effect of certain medications: Some drugs include systemic glucocorticoids, phenytoin, and carbamazepine, have been associated with IgG deficiency.
  • Other causes of primary humoral immunodeficiencies.
  • Smoking: may cause IgG2 subclass deficiency.
  • Protein-losing conditions: enteropathies, nephrotic syndrome, burns, and other traumas may cause abnormal loss of immunoglobulins.

Differentiating Wiskott-Aldrich Syndrome From Other Bleeding Diseases

  • Wiskott-Aldrich syndrome must be differentiated from other bleeding disorders. Different causes of bleeding disorders can be differentiated based on their clinical manifestation and laboratory findings. These features have discussed in the below table:
Category Subcategory Disease History Clinical manifestation Laboratory testing Comments
Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT
Platelet disorders Qualitative Disorders of Platelet Function Inherited Disorders of Platelet Function Wiskott-Aldrich syndrome
  • Positive family history
+ + + + Nl or ↓ Nl Nl Nl
  • Anti-WASP antibody can be used to detect presence or absence of WAS protein
  • In Wiskott–Aldrich syndrome, the platelets are small and do not function properly. They are removed by the spleen, which leads to low platelet counts.
Glanzmann’s thrombasthenia
  • Positive family history
+ + + + Rare Nl or ↓ Nl Nl Nl
  • AR inheritance
  • Absence of the platelet Gp IIb/IIIa receptor
  • Diminished for GP 2B-3A on flow cytometry
Bernard-Soulier syndrome
  • Positive family history
+ + + + Nl or ↓ Nl Nl Nl
  • AR inheritance
  • Absence of the platelet Gp Ib-IX-V receptor
  • On PBS: giant platelets
  • Ristocetin - no aggregation
Platelet storage pool disorder: + + + + Nl or ↓ Nl Nl Nl
  • AD inheritance
  • AbNlities of platelet granule formation
Acquired Disorders of Platelet Function + + + + ± ± Nl or ↓ Nl Nl Nl
Von Willebrand Disease + + + + ± ± Nl Nl See the table below for the details about different types.
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Thrombocytopenia Infection-Induced thrombocytopenia
  • History of prior infection
+ + + + + + Nl Nl Nl
Medication-Induced Thrombocytopenia + + + + + + Nl Nl Nl Most important part of treatment is discontinuing of the medication.
Heparin-Induced thrombocytopenia + + + + + + Nl Nl For more information click here: Heparin-induced thrombocytopenia.
Immune Thrombocytopenic Purpura + + + + + + Nl Nl Nl
Inherited Thrombocytopenia
  • Positive family history
+ + + + + + Nl Nl Nl
Thrombotic Thrombocytopenic Purpura History of: + + + + + + Nl Nl Nl
Hemolytic Uremic Syndrome History of: + + + + + + Nl Nl Nl
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Vessel wall disorders Metabolic and Inflammatory Disorders
  • History of the underlying disease
+ + ± Nl Nl or ↑ Nl Nl Nl
Inherited Disorders of the Vessel Wall
  • Positive family history
+ + ± Nl Nl or ↑ Nl Nl Nl
Coagulation factor disorders

[57]

Fibrinogen deficiency

Different types of the fibrinogen disorders:

+ + ± + Nl
  • Impaired fibrin cross-linking or clot dissolution
  • Mild or severe bleeding idepend on levels of functional fibrinogen
  • Variable age of onset
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Prothrombin deficiency + + + + + Nl Nl
Factor V deficiency + + + + Nl Nl
  • The severity of bleeding related to the degree of factor V deficiency
Factor VII deficiency + + + Nl Nl Nl
  • Thrombosis in inherited factor VII deficiency
  • Treatment with the administration of factor VII replacement therapy
Factor X deficiency
  • Prolonged bleeding following circumcision
  • Easy bruising
  • Hematuria
  • Menorrhagia
  • Abortion
  • Postpartum hemorrhage
  • Epistaxis
  • Pseudotumors
  • Intracranial bleeding
  • Hemarthroses
+ + + + + Nl Nl Nl
Factor XII deficiency
  • Asymptomatic
  • Recurrent miscarriages
  • Painful leg ulcers
Nl Nl Nl Nl
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
High molecular weight kininogen (HMWK) deficiency
  • Positive family history of bleeding
Nl Nl Nl Nl
Prekallikrein deficiency
  • Positive family history of bleeding
Nl Nl Nl Nl
Factor XIII deficiency
  • Sub unit A mutation disease (more common)
  • Sub unit B mutation disease
  • Positive family history of bleeding
± ± ± ± ± ± Nl Nl Nl or ↑ Nl Nl
  • Impaired fibrin cross-linking or clot dissolution
  • The severity of factor XIII deficiency bleeds can be different in different patients
Hemophilia Type A deficiency + + + Nl Nl Nl Nl
Type B deficiency + + + Nl Nl Nl Nl
Type C deficiency
  • Positive family history
  • Bleeding after surgery or injury
+ Rare Rare Nl Nl Nl Nl
Subcategory Disease History Mucosal bleeding Petechia Ecchymoses Menorrhagia Hematoma Hemarthrosis Plt BT PT PTT TT Comments
Rare diseases Disseminated Intravascular Coagulation + + + + + + Nl
Vitamin K Deficiency + + + + + Nl Nl or mildly prolonged Nl

Risk Factors

  • Positive family history of Wiskott-Aldrich syndrome, can be considered as a risk factor.

Screening

  • Flow cytometry:
    • Anti-WASp antibody can be used to detect presence or absence of WAS protein. However, flow cytometry may not detect expression of mutated, reduced or poor WASp.[58]
  • Identification of carriers: Known female carriers can be identified by using DNA mutation analysis of WAS gene.
  • Prenatal diagnosis: DNA analysis from chorionic villus sampling can be performed.[59]

Natural History, Complications, and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

  • Patients with Wiskott-Aldrich syndrome have

Physical Examination

Laboratory Findings

Electrocardiogram

  • There are no specific electrocardiogram findings associated with Wiskott-Aldrich syndrome.

X-ray

  • There are no specific x-ray findings associated with Wiskott-Aldrich syndrome. However, a chest x-ray may be helpful in the diagnosis of complications, which include pneumonia.

Echocardiography or Ultrasound

CT scan

MRI

  • There are no specific MRI findings associated with Wiskott-Aldrich syndrome.

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

References

  1. Aldrich RA, Steinberg AG, Campbell DC (1954). "Pedigree demonstrating a sex-linked recessive condition characterized by draining ears, eczematoid dermatitis and bloody diarrhea". Pediatrics. 13 (2): 133–9. PMID 13133561. 
  2. Wiskott, A (1937). "Familiärer, angeborener Morbus Werlhofii? ("Familial congenital Werlhof's disease?")". Montsschr Kinderheilkd. 68: 212–16. 
  3. Binder V, Albert MH, Kabus M, Bertone M, Meindl A, Belohradsky BH (2006). "The genotype of the original Wiskott phenotype". N. Engl. J. Med. 355 (17): 1790–3. PMID 17065640. doi:10.1056/NEJMoa062520. 
  4. Jin Y, Mazza C, Christie JR; et al. (2004). "Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation". Blood. 104 (13): 4010–9. PMID 15284122. doi:10.1182/blood-2003-05-1592. 
  5. 5.0 5.1 "Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01. 
  6. 6.0 6.1 PMID 1683685 (PubMed)
    Citation will be completed automatically in a few minutes. Jump the queue or expand by hand
  7. Agarwal S, Cunningham-Rundles C (September 2007). "Assessment and clinical interpretation of reduced IgG values". Ann. Allergy Asthma Immunol. 99 (3): 281–3. PMC 3099256Freely accessible. PMID 17910333. doi:10.1016/S1081-1206(10)60665-5. 
  8. Korthäuer U, Graf D, Mages HW, Brière F, Padayachee M, Malcolm S, Ugazio AG, Notarangelo LD, Levinsky RJ, Kroczek RA (February 1993). "Defective expression of T-cell CD40 ligand causes X-linked immunodeficiency with hyper-IgM". Nature. 361 (6412): 539–41. PMID 7679206. doi:10.1038/361539a0. 
  9. Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, Resnick I, Fasth A, Baer M, Gomez L, Sanders EA, Tabone MD, Plantaz D, Etzioni A, Monafo V, Abinun M, Hammarstrom L, Abrahamsen T, Jones A, Finn A, Klemola T, DeVries E, Sanal O, Peitsch MC, Notarangelo LD (July 1997). "Clinical spectrum of X-linked hyper-IgM syndrome". J. Pediatr. 131 (1 Pt 1): 47–54. PMID 9255191. 
  10. Winkelstein JA, Marino MC, Ochs H, Fuleihan R, Scholl PR, Geha R, Stiehm ER, Conley ME (November 2003). "The X-linked hyper-IgM syndrome: clinical and immunologic features of 79 patients". Medicine (Baltimore). 82 (6): 373–84. PMID 14663287. doi:10.1097/01.md.0000100046.06009.b0. 
  11. Subauste CS, Wessendarp M, Sorensen RU, Leiva LE (June 1999). "CD40-CD40 ligand interaction is central to cell-mediated immunity against Toxoplasma gondii: patients with hyper IgM syndrome have a defective type 1 immune response that can be restored by soluble CD40 ligand trimer". J. Immunol. 162 (11): 6690–700. PMID 10352287. 
  12. Hayward AR, Levy J, Facchetti F, Notarangelo L, Ochs HD, Etzioni A, Bonnefoy JY, Cosyns M, Weinberg A (January 1997). "Cholangiopathy and tumors of the pancreas, liver, and biliary tree in boys with X-linked immunodeficiency with hyper-IgM". J. Immunol. 158 (2): 977–83. PMID 8993019. 
  13. Davies EG, Thrasher AJ (April 2010). "Update on the hyper immunoglobulin M syndromes". Br. J. Haematol. 149 (2): 167–80. PMC 2855828Freely accessible. PMID 20180797. doi:10.1111/j.1365-2141.2010.08077.x. 
  14. Yel L (January 2010). "Selective IgA deficiency". J. Clin. Immunol. 30 (1): 10–6. PMC 2821513Freely accessible. PMID 20101521. doi:10.1007/s10875-009-9357-x. 
  15. Suzuki H, Kaneko H, Fukao T, Jin R, Kawamoto N, Asano T, Matsui E, Kasahara K, Kondo N (March 2009). "Various expression patterns of alpha1 and alpha2 genes in IgA deficiency". Allergol Int. 58 (1): 111–7. PMID 19153537. doi:10.2332/allergolint.O-08-549. 
  16. Cunningham-Rundles C (September 2001). "Physiology of IgA and IgA deficiency". J. Clin. Immunol. 21 (5): 303–9. PMID 11720003. 
  17. Edwards E, Razvi S, Cunningham-Rundles C (April 2004). "IgA deficiency: clinical correlates and responses to pneumococcal vaccine". Clin. Immunol. 111 (1): 93–7. PMID 15093556. doi:10.1016/j.clim.2003.12.005. 
  18. Chipps BE, Talamo RC, Winkelstein JA (April 1978). "IgA deficiency, recurrent pneumonias, and bronchiectasis". Chest. 73 (4): 519–26. PMID 305332. 
  19. Zinneman HH, Kaplan AP (September 1972). "The association of giardiasis with reduced intestinal secretory immunoglobulin A". Am J Dig Dis. 17 (9): 793–7. PMID 5056860. 
  20. Aghamohammadi A, Cheraghi T, Gharagozlou M, Movahedi M, Rezaei N, Yeganeh M, Parvaneh N, Abolhassani H, Pourpak Z, Moin M (January 2009). "IgA deficiency: correlation between clinical and immunological phenotypes". J. Clin. Immunol. 29 (1): 130–6. PMID 18683032. doi:10.1007/s10875-008-9229-9. 
  21. Janzi M, Kull I, Sjöberg R, Wan J, Melén E, Bayat N, Ostblom E, Pan-Hammarström Q, Nilsson P, Hammarström L (October 2009). "Selective IgA deficiency in early life: association to infections and allergic diseases during childhood". Clin. Immunol. 133 (1): 78–85. PMID 19541543. doi:10.1016/j.clim.2009.05.014. 
  22. Jacob CM, Pastorino AC, Fahl K, Carneiro-Sampaio M, Monteiro RC (May 2008). "Autoimmunity in IgA deficiency: revisiting the role of IgA as a silent housekeeper". J. Clin. Immunol. 28 Suppl 1: S56–61. PMID 18202833. doi:10.1007/s10875-007-9163-2. 
  23. Conley ME, Notarangelo LD, Etzioni A (December 1999). "Diagnostic criteria for primary immunodeficiencies. Representing PAGID (Pan-American Group for Immunodeficiency) and ESID (European Society for Immunodeficiencies)". Clin. Immunol. 93 (3): 190–7. PMID 10600329. doi:10.1006/clim.1999.4799. 
  24. Mayer RJ, Schiffer CA, Peterson BA, Silver RT, Cornwell GG, McIntyre OR, Rai KR, Budman DR, Ellison RR, Maguire M (June 1985). "Intensive postremission therapy in adults with acute nonlymphocytic leukemia with ara-C by continuous infusion or bolus administration: preliminary results of a CALGB phase I study". Semin. Oncol. 12 (2 Suppl 3): 84–90. PMID 4012343. 
  25. Massaad MJ, Ramesh N, Geha RS (May 2013). "Wiskott-Aldrich syndrome: a comprehensive review". Ann. N. Y. Acad. Sci. 1285: 26–43. PMID 23527602. doi:10.1111/nyas.12049. 
  26. Candotti F (January 2018). "Clinical Manifestations and Pathophysiological Mechanisms of the Wiskott-Aldrich Syndrome". J. Clin. Immunol. 38 (1): 13–27. PMID 29086100. doi:10.1007/s10875-017-0453-z. 
  27. Sereni L, Castiello MC, Villa A (March 2018). "Platelets in Wiskott-Aldrich syndrome: Victims or executioners?". J. Leukoc. Biol. 103 (3): 577–590. PMID 28851742. doi:10.1189/jlb.5MR0617-257R. 
  28. Blundell MP, Worth A, Bouma G, Thrasher AJ (2010). "The Wiskott-Aldrich syndrome: The actin cytoskeleton and immune cell function". Dis. Markers. 29 (3-4): 157–75. PMC 3835520Freely accessible. PMID 21178275. doi:10.3233/DMA-2010-0735. 
  29. Bosticardo M, Marangoni F, Aiuti A, Villa A, Grazia Roncarolo M (June 2009). "Recent advances in understanding the pathophysiology of Wiskott-Aldrich syndrome". Blood. 113 (25): 6288–95. PMID 19351959. doi:10.1182/blood-2008-12-115253. 
  30. 30.0 30.1 Fischer A (November 2000). "Severe combined immunodeficiencies (SCID)". Clin. Exp. Immunol. 122 (2): 143–9. PMC 1905779Freely accessible. PMID 11091267. 
  31. Noguchi M, Yi H, Rosenblatt HM, Filipovich AH, Adelstein S, Modi WS, McBride OW, Leonard WJ (April 1993). "Interleukin-2 receptor gamma chain mutation results in X-linked severe combined immunodeficiency in humans". Cell. 73 (1): 147–57. PMID 8462096. 
  32. Puck JM (November 1996). "IL2RGbase: a database of gamma c-chain defects causing human X-SCID". Immunol. Today. 17 (11): 507–11. PMID 8961626. 
  33. Rowiński J, Souchier C, Czyba JC (1978). "DNA content of cells in human buccal smears. A preliminary study". Acta Histochem. 62 (2): 276–81. PMID 104530. doi:10.1016/S0065-1281(78)80093-2. 
  34. Morgan G, Levinsky RJ, Hugh-Jones K, Fairbanks LD, Morris GS, Simmonds HA (December 1987). "Heterogeneity of biochemical, clinical and immunological parameters in severe combined immunodeficiency due to adenosine deaminase deficiency". Clin. Exp. Immunol. 70 (3): 491–9. PMC 1542189Freely accessible. PMID 3436096. 
  35. Ballard RW, Cummings CW (August 1980). "Job's syndrome". Laryngoscope. 90 (8 Pt 1): 1367–70. PMID 7401839. 
  36. Freeman AF, Holland SM (May 2008). "The hyper-IgE syndromes". Immunol Allergy Clin North Am. 28 (2): 277–91, viii. PMC 2683262Freely accessible. PMID 18424333. doi:10.1016/j.iac.2008.01.005. 
  37. Holland SM, DeLeo FR, Elloumi HZ, Hsu AP, Uzel G, Brodsky N, Freeman AF, Demidowich A, Davis J, Turner ML, Anderson VL, Darnell DN, Welch PA, Kuhns DB, Frucht DM, Malech HL, Gallin JI, Kobayashi SD, Whitney AR, Voyich JM, Musser JM, Woellner C, Schäffer AA, Puck JM, Grimbacher B (October 2007). "STAT3 mutations in the hyper-IgE syndrome". N. Engl. J. Med. 357 (16): 1608–19. PMID 17881745. doi:10.1056/NEJMoa073687. 
  38. Ling JC, Freeman AF, Gharib AM, Arai AE, Lederman RJ, Rosing DR, Holland SM (March 2007). "Coronary artery aneurysms in patients with hyper IgE recurrent infection syndrome". Clin. Immunol. 122 (3): 255–8. PMID 17098478. doi:10.1016/j.clim.2006.10.005. 
  39. Hutto JO, Bryan CS, Greene FL, White CJ, Gallin JI (March 1988). "Cryptococcosis of the colon resembling Crohn's disease in a patient with the hyperimmunoglobulinemia E-recurrent infection (Job's) syndrome". Gastroenterology. 94 (3): 808–12. PMID 3338649. 
  40. O'Connell AC, Puck JM, Grimbacher B, Facchetti F, Majorana A, Gallin JI, Malech HL, Holland SM (February 2000). "Delayed eruption of permanent teeth in hyperimmunoglobulinemia E recurrent infection syndrome". Oral Surg Oral Med Oral Pathol Oral Radiol Endod. 89 (2): 177–85. PMID 10673653. doi:10.1067/moe.2000.103129. 
  41. Tam JS, Routes JM (2013). "Common variable immunodeficiency". Am J Rhinol Allergy. 27 (4): 260–5. PMC 3901442Freely accessible. PMID 23883805. doi:10.2500/ajra.2013.27.3899. 
  42. Resnick ES, Moshier EL, Godbold JH, Cunningham-Rundles C (February 2012). "Morbidity and mortality in common variable immune deficiency over 4 decades". Blood. 119 (7): 1650–7. PMC 3286343Freely accessible. PMID 22180439. doi:10.1182/blood-2011-09-377945. 
  43. Oksenhendler E, Gérard L, Fieschi C, Malphettes M, Mouillot G, Jaussaud R, Viallard JF, Gardembas M, Galicier L, Schleinitz N, Suarez F, Soulas-Sprauel P, Hachulla E, Jaccard A, Gardeur A, Théodorou I, Rabian C, Debré P (May 2008). "Infections in 252 patients with common variable immunodeficiency". Clin. Infect. Dis. 46 (10): 1547–54. PMID 18419489. doi:10.1086/587669. 
  44. Roifman CM, Rao CP, Lederman HM, Lavi S, Quinn P, Gelfand EW (April 1986). "Increased susceptibility to Mycoplasma infection in patients with hypogammaglobulinemia". Am. J. Med. 80 (4): 590–4. PMID 3963038. 
  45. Yong PF, Thaventhiran JE, Grimbacher B (2011). ""A rose is a rose is a rose," but CVID is Not CVID common variable immune deficiency (CVID), what do we know in 2011?". Adv. Immunol. 111: 47–107. PMID 21970952. doi:10.1016/B978-0-12-385991-4.00002-7. 
  46. Salzer U, Chapel HM, Webster AD, Pan-Hammarström Q, Schmitt-Graeff A, Schlesier M, Peter HH, Rockstroh JK, Schneider P, Schäffer AA, Hammarström L, Grimbacher B (August 2005). "Mutations in TNFRSF13B encoding TACI are associated with common variable immunodeficiency in humans". Nat. Genet. 37 (8): 820–8. PMID 16007087. doi:10.1038/ng1600. 
  47. Quinti I, Soresina A, Spadaro G, Martino S, Donnanno S, Agostini C, Claudio P, Franco D, Maria Pesce A, Borghese F, Guerra A, Rondelli R, Plebani A (May 2007). "Long-term follow-up and outcome of a large cohort of patients with common variable immunodeficiency". J. Clin. Immunol. 27 (3): 308–16. PMID 17510807. doi:10.1007/s10875-007-9075-1. 
  48. Nissenkorn A, Ben-Zeev B (2015). "Ataxia telangiectasia". Handb Clin Neurol. 132: 199–214. PMID 26564081. doi:10.1016/B978-0-444-62702-5.00014-7. 
  49. Rothblum-Oviatt C, Wright J, Lefton-Greif MA, McGrath-Morrow SA, Crawford TO, Lederman HM (November 2016). "Ataxia telangiectasia: a review". Orphanet J Rare Dis. 11 (1): 159. PMC 5123280Freely accessible. PMID 27884168. doi:10.1186/s13023-016-0543-7. 
  50. Crawford TO (December 1998). "Ataxia telangiectasia". Semin Pediatr Neurol. 5 (4): 287–94. PMID 9874856. 
  51. Boder E (1985). "Ataxia-telangiectasia: an overview". Kroc Found Ser. 19: 1–63. PMID 2415689. 
  52. Hoche F, Seidel K, Theis M, Vlaho S, Schubert R, Zielen S, Kieslich M (June 2012). "Neurodegeneration in ataxia telangiectasia: what is new? What is evident?". Neuropediatrics. 43 (3): 119–29. PMID 22614068. doi:10.1055/s-0032-1313915. 
  53. BODER E, SEDGWICK RP (April 1958). "Ataxia-telangiectasia; a familial syndrome of progressive cerebellar ataxia, oculocutaneous telangiectasia and frequent pulmonary infection". Pediatrics. 21 (4): 526–54. PMID 13542097. 
  54. Sahama I, Sinclair K, Pannek K, Lavin M, Rose S (August 2014). "Radiological imaging in ataxia telangiectasia: a review". Cerebellum. 13 (4): 521–30. PMID 24683014. doi:10.1007/s12311-014-0557-4. 
  55. Lin DD, Barker PB, Lederman HM, Crawford TO (January 2014). "Cerebral abnormalities in adults with ataxia-telangiectasia". AJNR Am J Neuroradiol. 35 (1): 119–23. PMC 4106125Freely accessible. PMID 23886747. doi:10.3174/ajnr.A3646. 
  56. Nowak-Wegrzyn A, Crawford TO, Winkelstein JA, Carson KA, Lederman HM (April 2004). "Immunodeficiency and infections in ataxia-telangiectasia". J. Pediatr. 144 (4): 505–11. PMID 15069401. doi:10.1016/j.jpeds.2003.12.046. 
  57. Chiang S, Vergamini SM, Husami A, Neumeier L, Quinn K, Ellerhorst T, Sheppard L, Gifford C, Buchbinder D, Joshi A, Ifversen M, Kleiner GI, Bussel JB, Chandrakasan S, Pesek RD, Pozos TC, Rose MJ, Scurlock AM, Zhang K, Bryceson YT, Bleesing J, Marsh RA (July 2018). "Screening for Wiskott-Aldrich syndrome by flow cytometry". J. Allergy Clin. Immunol. 142 (1): 333–335.e8. PMID 29729304. doi:10.1016/j.jaci.2018.04.017. 
  58. 59.0 59.1 Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD (January 1999). "Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis". Prenat. Diagn. 19 (1): 36–40. PMID 10073904. 
  59. 60.0 60.1 Sullivan KE, Mullen CA, Blaese RM, Winkelstein JA (December 1994). "A multiinstitutional survey of the Wiskott-Aldrich syndrome". J. Pediatr. 125 (6 Pt 1): 876–85. PMID 7996359. 
  60. WEINTRAUB HD, WILSON WJ (August 1964). "PNEUMOCYSTIS CARINII PNEUMONIA IN WISKOTT-ALDRICH SYNDROME". Am. J. Dis. Child. 108: 198–200. PMID 14159941. 
  61. Blancas-Galicia L, Escamilla-Quiroz C, Yamazaki-Nakashimada MA (2011). "[Wiskott-Aldrich Syndrome: An updated review]". Rev Alerg Mex (in Spanish; Castilian). 58 (4): 213–8. PMID 24007832. 
  62. 63.0 63.1 Imai K, Morio T, Zhu Y, Jin Y, Itoh S, Kajiwara M, Yata J, Mizutani S, Ochs HD, Nonoyama S (January 2004). "Clinical course of patients with WASP gene mutations". Blood. 103 (2): 456–64. PMID 12969986. doi:10.1182/blood-2003-05-1480. 
  63. Notarangelo LD (February 2013). "In Wiskott-Aldrich syndrome, platelet count matters". Blood. 121 (9): 1484–5. PMID 23449611. doi:10.1182/blood-2013-01-475913. 
  64. Dupuis-Girod S, Medioni J, Haddad E, Quartier P, Cavazzana-Calvo M, Le Deist F, de Saint Basile G, Delaunay J, Schwarz K, Casanova JL, Blanche S, Fischer A (May 2003). "Autoimmunity in Wiskott-Aldrich syndrome: risk factors, clinical features, and outcome in a single-center cohort of 55 patients". Pediatrics. 111 (5 Pt 1): e622–7. PMID 12728121. 
  65. Chen N, Zhang ZY, Liu DW, Liu W, Tang XM, Zhao XD (October 2015). "The clinical features of autoimmunity in 53 patients with Wiskott-Aldrich syndrome in China: a single-center study". Eur. J. Pediatr. 174 (10): 1311–8. PMID 25877044. doi:10.1007/s00431-015-2527-3. 
  66. Ohya T, Yanagimachi M, Iwasawa K, Umetsu S, Sogo T, Inui A, Fujisawa T, Ito S (December 2017). "Childhood-onset inflammatory bowel diseases associated with mutation of Wiskott-Aldrich syndrome protein gene". World J. Gastroenterol. 23 (48): 8544–8552. PMC 5752714Freely accessible. PMID 29358862. doi:10.3748/wjg.v23.i48.8544. 
  67. Cotelingam JD, Witebsky FG, Hsu SM, Blaese RM, Jaffe ES (1985). "Malignant lymphoma in patients with the Wiskott-Aldrich syndrome". Cancer Invest. 3 (6): 515–22. PMID 3910193. 
  68. Yoshimi A, Kamachi Y, Imai K, Watanabe N, Nakadate H, Kanazawa T, Ozono S, Kobayashi R, Yoshida M, Kobayashi C, Hama A, Muramatsu H, Sasahara Y, Jakob M, Morio T, Ehl S, Manabe A, Niemeyer C, Kojima S (May 2013). "Wiskott-Aldrich syndrome presenting with a clinical picture mimicking juvenile myelomonocytic leukaemia". Pediatr Blood Cancer. 60 (5): 836–41. PMID 23023736. doi:10.1002/pbc.24359. 
  69. Kobayashi R, Ariga T, Nonoyama S, Kanegane H, Tsuchiya S, Morio T, Yabe H, Nagatoshi Y, Kawa K, Tabuchi K, Tsuchida M, Miyawaki T, Kato S (November 2006). "Outcome in patients with Wiskott-Aldrich syndrome following stem cell transplantation: an analysis of 57 patients in Japan". Br. J. Haematol. 135 (3): 362–6. PMID 17032176. doi:10.1111/j.1365-2141.2006.06297.x. 
  70. Jin Y, Mazza C, Christie JR, Giliani S, Fiorini M, Mella P, Gandellini F, Stewart DM, Zhu Q, Nelson DL, Notarangelo LD, Ochs HD (December 2004). "Mutations of the Wiskott-Aldrich Syndrome Protein (WASP): hotspots, effect on transcription, and translation and phenotype/genotype correlation". Blood. 104 (13): 4010–9. PMID 15284122. doi:10.1182/blood-2003-05-1592. 
  71. Suri D, Singh S, Rawat A, Gupta A, Kamae C, Honma K, Nakagawa N, Imai K, Nonoyama S, Oshima K, Mitsuiki N, Ohara O, Bilhou-Nabera C, Proust A, Ahluwalia J, Dogra S, Saikia B, Minz RW, Sehgal S (March 2012). "Clinical profile and genetic basis of Wiskott-Aldrich syndrome at Chandigarh, North India". Asian Pac. J. Allergy Immunol. 30 (1): 71–8. PMID 22523910. 
  72. De Bernardi A, Chessa Ricotti G, Galli L, Funis M (1990). "[Wiskott-Aldrich syndrome: description of a clinical case]". Pediatr Med Chir (in Italian). 12 (6): 691–3. PMID 2093894. 
  73. Ochs HD, Slichter SJ, Harker LA, Von Behrens WE, Clark RA, Wedgwood RJ (February 1980). "The Wiskott-Aldrich syndrome: studies of lymphocytes, granulocytes, and platelets". Blood. 55 (2): 243–52. PMID 6444359. 
  74. Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. PMC 4012343Freely accessible. PMID 24817816. doi:10.2147/TACG.S58444. 
  75. Humblet-Baron S, Sather B, Anover S, Becker-Herman S, Kasprowicz DJ, Khim S, Nguyen T, Hudkins-Loya K, Alpers CE, Ziegler SF, Ochs H, Torgerson T, Campbell DJ, Rawlings DJ (February 2007). "Wiskott-Aldrich syndrome protein is required for regulatory T cell homeostasis". J. Clin. Invest. 117 (2): 407–18. PMC 1764857Freely accessible. PMID 17218989. doi:10.1172/JCI29539. 
  76. Orange JS, Ramesh N, Remold-O'Donnell E, Sasahara Y, Koopman L, Byrne M, Bonilla FA, Rosen FS, Geha RS, Strominger JL (August 2002). "Wiskott-Aldrich syndrome protein is required for NK cell cytotoxicity and colocalizes with actin to NK cell-activating immunologic synapses". Proc. Natl. Acad. Sci. U.S.A. 99 (17): 11351–6. PMC 123260Freely accessible. PMID 12177428. doi:10.1073/pnas.162376099. 
  77. Wu EY, Ehrlich L, Handly B, Frush DP, Buckley RH (November 2016). "Clinical and imaging considerations in primary immunodeficiency disorders: an update". Pediatr Radiol. 46 (12): 1630–1644. PMC 5083248Freely accessible. PMID 27655432. doi:10.1007/s00247-016-3684-x. 
  78. Litzman J, Jones A, Hann I, Chapel H, Strobel S, Morgan G (November 1996). "Intravenous immunoglobulin, splenectomy, and antibiotic prophylaxis in Wiskott-Aldrich syndrome". Arch. Dis. Child. 75 (5): 436–9. PMC 1511781Freely accessible. PMID 8957959. 
  79. Kim KR, Kim JM, Kang JM, Kim YJ (June 2016). "Pneumocystis jirovecii pneumonia in pediatric patients: an analysis of 15 confirmed consecutive cases during 14 years". Korean J Pediatr. 59 (6): 252–5. PMC 4958702Freely accessible. PMID 27462353. doi:10.3345/kjp.2016.59.6.252. 
  80. Modiano P, Salloum E, Gillet-Terver MN, Barbaud A, Georges JC, Thouvenot D, Schmutz JL, Weber M (September 1995). "Acyclovir-resistant chronic cutaneous herpes simplex in Wiskott-Aldrich syndrome". Br. J. Dermatol. 133 (3): 475–8. PMID 8547009. 
  81. Ferrara M, Capozzi L, Coppola A, Save G, Coppola L (August 2007). "Prophylactic platelet transfusion in children with thrombocytopenic disorders: a retrospective review". Hematology. 12 (4): 297–9. PMID 17654055. doi:10.1080/10245330701255213. 
  82. Blaese RM, Strober W, Levy AL, Waldmann TA (November 1971). "Hypercatabolism of IgG, IgA, IgM, and albumin in the Wiskott-Aldrich syndrome. A unique disorder of serum protein metabolism". J. Clin. Invest. 50 (11): 2331–8. PMC 292175Freely accessible. PMID 5096517. doi:10.1172/JCI106731. 
  83. Kim JJ, Thrasher AJ, Jones AM, Davies EG, Cale CM (July 2007). "Rituximab for the treatment of autoimmune cytopenias in children with immune deficiency". Br. J. Haematol. 138 (1): 94–6. PMID 17498197. doi:10.1111/j.1365-2141.2007.06616.x. 
  84. Gerrits AJ, Leven EA, Frelinger AL, Brigstocke SL, Berny-Lang MA, Mitchell WB, Revel-Vilk S, Tamary H, Carmichael SL, Barnard MR, Michelson AD, Bussel JB (September 2015). "Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia". Blood. 126 (11): 1367–78. PMC 4729539Freely accessible. PMID 26224646. doi:10.1182/blood-2014-09-602573. 
  85. Boztug K, Schmidt M, Schwarzer A, Banerjee PP, Díez IA, Dewey RA, Böhm M, Nowrouzi A, Ball CR, Glimm H, Naundorf S, Kühlcke K, Blasczyk R, Kondratenko I, Maródi L, Orange JS, von Kalle C, Klein C (November 2010). "Stem-cell gene therapy for the Wiskott-Aldrich syndrome". N. Engl. J. Med. 363 (20): 1918–27. PMC 3064520Freely accessible. PMID 21067383. doi:10.1056/NEJMoa1003548. 
  86. Bach FH, Albertini RJ, Joo P, Anderson JL, Bortin MM (December 1968). "Bone-marrow transplantation in a patient with the Wiskott-Aldrich syndrome". Lancet. 2 (7583): 1364–6. PMID 4177931. 
  87. Antoine C, Müller S, Cant A, Cavazzana-Calvo M, Veys P, Vossen J, Fasth A, Heilmann C, Wulffraat N, Seger R, Blanche S, Friedrich W, Abinun M, Davies G, Bredius R, Schulz A, Landais P, Fischer A (February 2003). "Long-term survival and transplantation of haemopoietic stem cells for immunodeficiencies: report of the European experience 1968-99". Lancet. 361 (9357): 553–60. PMID 12598139. 
  88. Muñoz A, Olivé T, Martinez A, Bureo E, Maldonado MS, Diaz de Heredia C, Sastre A, Gonzalez-Vicent M (September 2007). "Allogeneic hemopoietic stem cell transplantation (HSCT) for Wiskott-Aldrich syndrome: a report of the Spanish Working Party for Blood and Marrow Transplantation in Children (GETMON)". Pediatr Hematol Oncol. 24 (6): 393–402. PMID 17710656. doi:10.1080/08880010701454404. 
  89. Lum LG, Tubergen DG, Corash L, Blaese RM (April 1980). "Splenectomy in the management of the thrombocytopenia of the Wiskott-Aldrich syndrome". N. Engl. J. Med. 302 (16): 892–6. PMID 6767187. doi:10.1056/NEJM198004173021604. 
  90. Syrigos KN, Makrilia N, Neidhart J, Moutsos M, Tsimpoukis S, Kiagia M, Saif MW (September 2011). "Prolonged survival after splenectomy in Wiskott-Aldrich syndrome: a case report". Ital J Pediatr. 37: 42. PMC 3179709Freely accessible. PMID 21906397. doi:10.1186/1824-7288-37-42. 
  91. Derry JM, Ochs HD, Francke U (August 1994). "Isolation of a novel gene mutated in Wiskott-Aldrich syndrome". Cell. 78 (4): 635–44. PMID 8069912. 




Linked-in.jpg