WAS and WIPF1 genes

Also known as: Wiskott-Aldrich syndrome 1 (WAS1); Aldrich syndrome; Eczema-thrombocytopenia-immunodeficiency syndrome; Immunodeficiency 2


– OMIM#301000 https://omim.org/entry/301000

– OMIM#614493 https://omim.org/entry/614493

1. The disease:

A primary immunodeficiency disease characterized by microthrombocytopenia, eczema, infections and an increased risk for autoimmune manifestations and malignancies.

2. The symptoms:

WAS usually manifests in infancy but onset may also occur during the neonatal period. In most cases the first clinical features are hemorrhagic manifestations with petechiae, bruising, purpura, epistaxis, oral bleeding, bloody diarrhea and intracranial bleeding. Acute or chronic eczema is the second characteristic finding of WAS. Due to combined immunodeficiency, most patients also have airway, gut or skin infections caused by regular or opportunistic germs. Autoimmune manifestations are seen in approximately 40% of cases and include autoimmune hemolytic anemia, neutropenia, vasculitis, inflammatory bowel disease, renal disease, and arthritis. WAS patients have a higher risk of developing tumors (mainly B-cell lymphomas) at any age.

3. Actions to take in case of early diagnosis:

  • Usually, hypomorphic mutations in the WAS gene can lead to an attenuated form of WAS called X-linked thrombocytopenia with normal platelets (XLTT), that is characterized by mild to moderate thrombocytopenia and eczema and a lower risk of autoimmunity and malignancy, but usually showing no immunodeficiency.
  • Correlation with laboratorial findings as severe thrombocytopenia with reduced platelet size with a usually normal number of megakaryocytes, as well as altered antibody production (mainly antipolysaccharidic antibodies) can help in the diagnosis.
  • WAS is a lifelong disease requiring lifetime management and regular follow-up with a Haematology Center. Management is provided by multidisciplinary team.
  • Supportive care includes transfusions of packed red blood cells (RBC) or leucodepleted platelets but if regular transfusion is required, hematopoietic stem cell transplantation (HSCT) should be considered.
  • The only curative treatment to date is hematopoietic stem cell transplantation (HSCT), performed as soon as possible with the best matched HLA donor. In young patients lacking a HLA matched donor, HSCT with a haploidentical donor can lead to a favourable outcome.
  • Gene therapy with lentiviral vector, still experimental to date, may be a promising approach for patients lacking a suitable donor.
  • Immunoglobulin replacement therapy and oral antibiotics prevent infections.
  • Severe eczema requires treatment with topical or short-term systemic steroids. Treatments that could weaken the immune system (steroids, splenectomy, immunosuppressive agents) should be used with the highest caution by trained medical staff.
  • Agonists of the thrombopoietin receptors (such as romiplostim and eltrombopag) can be used to increase the platelet count in severe refractory thrombocytopenia cases that are awaiting HSCT or gene therapy.
  • Agents/circumstances to avoid: Circumcision of at-risk newborn males who have thrombocytopenia; use of medications that interfere with platelet function. Defer elective procedures until after HCT.
  • Genetic counselling should be offered to at-risk family members.

4. For more information:

Orphanet : https://www.orpha.net/consor/cgi-bin/Disease_Search.php?lng=EN&data_id=144&Disease_Disease_Search_diseaseGroup=wiskott-aldrich&Disease_Disease_Search_diseaseType=Pat&Disease(s)/group%20of%20diseases=Wiskott-Aldrich-syndrome&title=Wiskott-Aldrich%20syndrome&search=Disease_Search_Simple

Biblio : https://www.ncbi.nlm.nih.gov/books/NBK1178/