Wiskott-Aldrich syndrome: Difference between revisions
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==Screening== | ==Screening== | ||
*[[Flow cytometry]]: | *[[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 | ** 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.<ref name="pmid29729304">{{cite journal |vauthors=Chiang SCC, 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 |title=Screening for Wiskott-Aldrich syndrome by flow cytometry |journal=J. Allergy Clin. Immunol. |volume=142 |issue=1 |pages=333–335.e8 |date=July 2018 |pmid=29729304 |doi=10.1016/j.jaci.2018.04.017 |url=}}</ref> | ||
* Identification of carriers: Known [[female]] carriers can be identified by using [[DNA]] mutation analysis | * 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.<ref name="pmid10073904">{{cite journal |vauthors=Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD |title=Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis |journal=Prenat. Diagn. |volume=19 |issue=1 |pages=36–40 |date=January 1999 |pmid=10073904 |doi= |url=}}</ref> | * Prenatal diagnosis: DNA analysis from [[chorionic villus sampling]] can be performed.<ref name="pmid10073904">{{cite journal |vauthors=Giliani S, Fiorini M, Mella P, Candotti F, Schumacher RF, Wengler GS, Lalatta F, Fasth A, Badolato R, Ugazio AG, Albertini A, Notarangelo LD |title=Prenatal molecular diagnosis of Wiskott-Aldrich syndrome by direct mutation analysis |journal=Prenat. Diagn. |volume=19 |issue=1 |pages=36–40 |date=January 1999 |pmid=10073904 |doi= |url=}}</ref> | ||
Revision as of 12:58, 23 August 2018
| Wiskott-Aldrich syndrome | |
| ICD-10 | D82.0 |
|---|---|
| ICD-9 | 279.12 |
| OMIM | 301000 |
| DiseasesDB | 14176 |
| MeSH | D014923 |
Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Chandrakala Yannam, MD [2]
Associate Editor-In-Chief: Cafer Zorkun, M.D., Ph.D. [3]
Synonyms and keywords: Aldrich syndrome
Patient Informtion
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]
- 0.5: intermittent thrombopenia
- 1.0: thrombopenia and small platelets
- 2.0: thrombopenia and normally responsive eczema or occasional upper respiratory tract infections.
- 2.5: thrombopenia and therapy-responsive but severe eczema or airway infections requiring antibiotics
- 3.0: both eczema and airway infections requiring antibiotics
- 4.0: eczema continuously requiring therapy and/or severe or life threatening infections
- 5.0: autoimmune disease or malignancy in an XLT/WAS patient.
Pathophysiology
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]
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 ((Page name)) from Other Diseases
Epidemiology and Demographics
The combined incidence of WAS and XLT is about 4-10 in 1 million live births. There is no geographical factor.
Risk Factors
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.[7]
- 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.[8]
Natural History, Complications, and Prognosis
- If left untreated, patients with Wiscott-Aldrich syndrome may progress to develop manifestations associated with thrombocytopenia, defective innate and adaptive immunity which include, severe bleeding (eg, epistaxis, purpura, life threatening gastrointestinal and intracranial hemorrhages), recurrent and severe bronchopulmonary infections. Malignancy and autoimmunity risk has also increased. These conditions may increase the risk of death.[9]
- Common complications of Wiscott-Aldrich syndrome include:
- Recurrent infections with bacterial, viral, fungal and opportunistic organisms. Most common clinical manifestations include otitis media, sinusitis, pneumonia, meningitis, skin infections, and sepsis.[10][11][12]
- Bleeding diathesis (eg, epistaxis, ecchymoses, petechiae, intracranial and gastrointestinal hemorrhages)[9][13]
- Autoimmune manifestations may occur in the form of autoimmune hemolytic anemia, immune thrombocytopenic purpura and neutropenia, vasculitis involving small and large vessels, inflammatory bowel disease, and immune-mediated damage to the kidneys and joints.[14][15][16]
- Increased risk of malignancy such as lymphoma, leukaemia is a frequent occurence in Wiskott-Aldrich syndrome.[17][18]
- Prognosis is generally poor. 5-year survival rates in patients with Wiscott-Aldrich syndrome who had received stem cell transplantation is approximately 73.7% to 80%.[19]
Diagnosis
Diagnostic Study of Choice
- The first laboratory test to be performed in the diagnosis of Wiskott-Aldrich syndrome is complete blood count with differential and peripheral blood smears.
- The diagnosis of Wiskott-Aldrich syndrome is suspected if a male patient who presents with bruises, petechiae and the presence of thrombocytopenia with small platelet volume (micro thrombocytopenia) on the peripheral blood smear.
- Identification of WAS gene mutations using DNA sequence analysis of WAS gene and detection of WASp expression by flow cytometry are necessary to confirm the diagnosis.[20][12]
History and Symptoms
- Common symptoms of Wiskott-Aldrich syndrome include:
- Easy bruising
- Petechiae
- Purpura
- Eczema
- Prolonged and excessive bleeding after circumcision or from umbilical stump
- Recurrent infections
- Epistaxis (Nose bleeds)
- Hematemesis
- Hematuria
- Melena
Physical Examination
- The following findings may be found in the physical examination of the patients with Wiscott-Aldrich syndrome. These include:[21][22]
- Failure to thrive
- Skin examination shows bruises, petechiae, purpura, and eczema due to low platelet count. suppurative skin lesions may also be seen.
- Lymphadenopathy
- Rales and wheezing on auscultation if there is an underlying lung infection.
- Hepatosplenomegaly
- ENT examination: Carefully examine sinuses to rule out sinusitis, ears for any tympanic membrane abnormalities to rule out otitis media and throat for pharyngitis and other opportunistic infections such as oral thrush.
- CNS examination may be performed for symptoms associated with intracranial hemorrhage and infections.
Laboratory Findings
- Laboratory findings consistent with the diagnosis of Wiscott-Aldrich syndrome include:
- Complete blood count (CBC) and peripheral smear may show anemia, thrombocytopenia, decreased platelet size and volume.[23]
- Immunologic studies may show following findings:[24][25][26]
- Decreased levels of serum IgG and IgM and elevated levels of serum IgA and IgE antibodies.
- Reduction in T lymphocyte count and their function.
- Variable antibody response to vaccines, protein and polysaccharide antigens.
- Decreased or absent concentrations of isohemagglutinins.
- Abnormal T and B lymphocyte proliferative response to mitogens.
- Abnormal phagocytic response
- Natural Killer cell defects may also be found.
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
- There are no specific echocardiography/ ultrasound findings associated with Wiscott-Aldrich syndrome.
CT scan
- There are no CT scan findings associated with Wiscott-Aldrich syndrome. However, a CT scan may be helpful in the diagnosis of complications of this syndrome, which include pneumonia, internal hemorrhage, to diagnose malignancy and to assess splenic enlargement.[27]
MRI
- There are no specific MRI findings associated with Wiskott-Aldrich syndrome.
Other Imaging Findings
- There are no other imaging findings associated with Wiscott-Aldrich syndrome.
Other Diagnostic Studies
- There are no other diagnostic tests associated with Wiskott-Aldrich syndrome.
Treatment
Medical Therapy
Treatment of Wiskott-Aldrich syndrome is based on correcting symptoms. Aspirin and other non-steroidal anti-inflammatory drugs should be avoided, since these may interfere with platelet function. A protective helmet can protect children from bleeding into the brain which could result from head injuries. For severely low platelet counts, patients may require platelet transfusions or a splenectomy. For patients with frequent infections, intravenous immunoglobulins (IVIG) can be given to boost the immune system. Anemia from bleeding may require iron supplementation or blood transfusion.
Surgery
- Splenectomy: Splenectomy may be considered for some patients with Wiskott-Aldrich syndrome . Splenectomy may be found to improve platelet count as well as size of the platelets . However, sepsis is a life-threatening complication after splenectomy. Prophylactic antibiotics should always be used to prevent infections.[28][29]
- Hematopoietic stem cell transplantation (HSCT):[30][31][32]
- HSCT is the only standard curative treatment for Wiskott-Aldrich syndrome.
Primary Prevention
- There are no established measures for the primary prevention of the Wiskott-Aldrich syndrome. However genetic mutation analysis and prenatal molecular diagnosis can be helpful.[33][8]
Secondary Prevention
- There are no established measures for the secondary prevention of the Wiskott-Aldrich syndrome.
References
- ↑ 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.
- ↑ Wiskott, A (1937). "Familiärer, angeborener Morbus Werlhofii? ("Familial congenital Werlhof's disease?")". Montsschr Kinderheilkd. 68: 212–16.
- ↑ 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. doi:10.1056/NEJMoa062520. PMID 17065640.
- ↑ 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. doi:10.1182/blood-2003-05-1592. PMID 15284122.
- ↑ 5.0 5.1 "Wiskott-Aldrich Syndrome: Immunodeficiency Disorders: Merck Manual Professional". Retrieved 2008-03-01.
- ↑ 6.0 6.1 PMID 1683685 (PMID 1683685)
Citation will be completed automatically in a few minutes. Jump the queue or expand by hand - ↑ 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. doi:10.1016/j.jaci.2018.04.017. PMID 29729304. Vancouver style error: initials (help)
- ↑ 8.0 8.1 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.
- ↑ 9.0 9.1 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.
- ↑ WEINTRAUB HD, WILSON WJ (August 1964). "PNEUMOCYSTIS CARINII PNEUMONIA IN WISKOTT-ALDRICH SYNDROME". Am. J. Dis. Child. 108: 198–200. PMID 14159941.
- ↑ 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.
- ↑ 12.0 12.1 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. doi:10.1182/blood-2003-05-1480. PMID 12969986.
- ↑ Notarangelo LD (February 2013). "In Wiskott-Aldrich syndrome, platelet count matters". Blood. 121 (9): 1484–5. doi:10.1182/blood-2013-01-475913. PMID 23449611.
- ↑ 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.
- ↑ 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. doi:10.1007/s00431-015-2527-3. PMID 25877044.
- ↑ 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. doi:10.3748/wjg.v23.i48.8544. PMC 5752714. PMID 29358862.
- ↑ 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.
- ↑ 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. doi:10.1002/pbc.24359. PMID 23023736.
- ↑ 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. doi:10.1111/j.1365-2141.2006.06297.x. PMID 17032176.
- ↑ 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. doi:10.1182/blood-2003-05-1592. PMID 15284122.
- ↑ 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.
- ↑ 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.
- ↑ 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.
- ↑ Buchbinder D, Nugent DJ, Fillipovich AH (2014). "Wiskott-Aldrich syndrome: diagnosis, current management, and emerging treatments". Appl Clin Genet. 7: 55–66. doi:10.2147/TACG.S58444. PMC 4012343. PMID 24817816.
- ↑ 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. doi:10.1172/JCI29539. PMC 1764857. PMID 17218989.
- ↑ 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. doi:10.1073/pnas.162376099. PMC 123260. PMID 12177428.
- ↑ 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. doi:10.1007/s00247-016-3684-x. PMC 5083248. PMID 27655432.
- ↑ 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. doi:10.1056/NEJM198004173021604. PMID 6767187.
- ↑ 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. doi:10.1186/1824-7288-37-42. PMC 3179709. PMID 21906397.
- ↑ 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.
- ↑ 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.
- ↑ 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. doi:10.1080/08880010701454404. PMID 17710656.
- ↑ 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.