Wiskott-Aldrich syndrome

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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. 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. 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.

Classification

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

• Grade 0.5: intermittent thrombopenia
• Grade 1.0: thrombopenia and small platelets
• Grade 2.0: thrombopenia and normally responsive eczema or occasional upper respiratory tract infections.
• Grade 2.5: thrombopenia and therapy-responsive but severe eczema or airway infections requiring antibiotics
• Grade 3.0: both eczema and airway infections requiring antibiotics
• Grade 4.0: eczema continuously requiring therapy and/or severe or life threatening infections
• Grade 5.0: autoimmune disease or malignancy in an XLT/WAS patient.

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 (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.

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 (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.

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:

Disorder	Mechanism	Characteristic Features	Clinical Presentation	Laboratory Findings
Wiskott-Aldrich Syndrome	Mutation in WAS gene T cells unable to reorganize actin microfilaments (microfilament defect)	X-linked recessive pattern of inheritance Increased risk of autoimmune disease and malignancy	Thrombocytopenic purpura Eczema Recurrent infections	Decreased to normal IgG and IgM Increased IgE and IgA Fewer and smaller platelets
X-Linked (Bruton) Agammaglobulinemia	Defect in tyrosine kinase gene (BTK) B cells fail to mature	X-linked recessive pattern of inheritance Increased prevalence in males	Recurrent bacterial and enteroviral infections after 6 months of age Pre-disposition to development of infections by encapsulated organisms Pre-disposition to development of Giardia infections Absent lymph nodes and tonsils	Normal CD19+ B cell count Decreased pro-B cells Increased pre-B cells Decreased immunoglobulins of all classes
Selective IgA Deficiency	Stem cell defect (Transferrable with marrow transplant) Lack of IL-4, IL-6, IL-7, IL-10, TGF-β, and IL-21 Mutations in transmembrane activator and calcium-modulator and cyclophilin ligand interactor (TACI, TNFRSF13B)	Most common primary immune deficiency	Majority of the cases are asymptomatic Respiratory and gastrointestinal infections (mucosal infections) Associated with autoimmune diseases Atopy Anaphylaxis to IgA containing products	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	May present with other autoimmune diseases Associated with bronchiectasis Associated with lymphoma Associated with sinopulmonary infections (Bacterial, enteroviral and parasitic such as Giardia)	Decreased plasma cells Decreased immunoglobulins
Autosomal dominant hype IgE syndrome (Job's Syndrome)	Defieciency of Th17 cells due to STAT3 mutation Impaired neutrophils to sites of infection	Distinctive coarse facies Cold (non-inflammatory) Staphylococcal abscesses Retained primary teeth Eczema		Increased levels of IgE Decreased levels of interferon gamma (IFN-gamma)
Severe combined immunodeficiency (SCID)	Defective interleukin-2 receptor gamma chain Adenosine deaminase deficiency Reg 1 and Reg 2 nonsense mutations	IL-2R disease is X-linked ADA deficiency and reg mutations are typically autosomal recessive	Failure to thrive Chronic diarrhea Thrush Recurrent bacterial, viral and protozoal infections Treatment is bone marrow transplant	Decreased T cell receptor excision circles (TRECs) Abscence of thymic shadow on chest X-Ray Absent germinal centers of lymph node biopsy Absent T cells on flow cytometry
Ataxia Telangiectasia	Defect in ATM gene DNA double stranded breaks leading to cell cycle arrest	Hypersensitivity to X-Rays	Triad of: Ataxia Spider angiomas (Nests of distended capillaries) IgA deficiency	Increased alpha fetoprotein (AFP) Decreased IgA, IgG and IgE Lymphopenia Cerebellar atrophy
Hyper IgM Syndrome	Defective CD40L (CD40 ligand) on Th cells leading to class switching defect	X-linked recessive pattern of inheritance	Severe pyogenic infections in early life Opportunistic infection with: Pneumocystis jiroveci Cryptosporidium Cytomegalovirus (CMV)	Increased IgM Decreased IgG, IgA and IgE No germinal centers

• 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: Hermansky-Pudlak syndrome Chediak-Higashi syndrome Gray platelet syndrome	Positive family history Hairy cell leukemia Cardiovascular bypass	+	+	+	+	−	−	Nl or ↓	↑	Nl	Nl	Nl	AD inheritance AbNlities of platelet granule formation
		Acquired Disorders of Platelet Function		Uremia Cardiopulmonary bypass Hematologic disorders such as: myeloproliferative and myelodysplastic syndromes	+	+	+	+	±	±	Nl or ↓	↑	Nl	Nl	Nl	−
		Von Willebrand Disease		Easy bruising Epistaxis Oral cavity bleeding Bleeding after dental extraction/surgery Menorrhagia Postpartum hemorrhage	+	+	+	+	±	±	↑	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		History of medications such as: Furosemide Nonsteroidal anti-inflammatory drugs (NSAIDs) Penicillin Quinidine Quinine Ranitidine Sulfonamides Linezolid	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	Most important part of treatment is discontinuing of the medication.
		Heparin-Induced thrombocytopenia		Thrombosis Unexplained thrombocytopenia up to 3 weeks after the end of heparin therapy	+	+	+	+	+	+	↓	↑	Nl	Nl	↑	For more information click here: Heparin-induced thrombocytopenia.
		Immune Thrombocytopenic Purpura		History of prior infection or no history	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Inherited Thrombocytopenia		Positive family history	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Thrombotic Thrombocytopenic Purpura		History of: Cancer Bone marrow transplantation Pregnancy Medication Platelet aggregation inhibitors (ticlopidine and clopidogrel) Immunosuppressants (cyclosporine, mitomycin, tacrolimus/FK506, interferon-α) HIV-1 infection	+	+	+	+	+	+	↓	↑	Nl	Nl	Nl	−
		Hemolytic Uremic Syndrome		History of: Infections Malignancy, chemotherapy, and ionizing radiation Calcineurin inhibitors and transplantation Pregnancy, HELLP syndrome, and oral contraceptive pill Systemic lupus erythematosis Antiphospholipid antibody syndrome Glomerulopathy	+	+	+	+	+	+	↓	↑	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	Acute febrile illnesses Mixed cryoglobulinemia Monoclonal gammopathies Rocky Mountain spotted fever Vitamin C deficiency Cushing’s syndrome Chronic glucocorticoid therapy Vasculitis such as Henoch-Schönlein Purpura		History of the underlying disease	−	+	+	±	−	−	Nl	Nl or ↑	Nl	Nl	Nl	−
	Inherited Disorders of the Vessel Wall	Marfan’s syndrome Ehlers-Danlos syndrome Pseudoxanthoma elasticum Hereditary hemorrhagic telangiectasia (HHT, or Osler-Weber-Rendu disease)		Positive family history	−	+	+	±	−	−	Nl	Nl or ↑	Nl	Nl	Nl	−
Coagulation factor disorders	Fibrinogen deficiency	Different types of the fibrinogen disorders: Congenital afibrinogenemia Congenital hypofibrinogenemia Fibrinogen storage disease Congenital dysfibrinogenemia Hereditary fibrinogen Aα-Chain amyloidosis Acquired dysfibrinogenemia		Epistaxis Easy bruising Menorrhagia Muscle bleeds Hemarthrosis Bleeding from the umbilical cord stump after birth Bleeding after dental surgery or tooth extraction AbNl bleeding during or after injury, surgery, or childbirth Gastrointestinal hemorrhage Cerebral hemorrhage Thrombosis	−	−	+	+	±	+	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			Epistaxis Soft-tissue hemorrhage Excessive postoperative bleeding Menorrhagia Muscle hematomas Hemarthrosis Intracranial bleeding	−	+	+	+	+	+	Nl	Nl	↑	↑	↑	−
	Factor V deficiency			Excessive bruising with minor injuries Epistaxis Hemarthrosis Menorrhagia Intracerebral hemorrhages Pulmonary hemorrhage	−	−	+	+	+	+	Nl	↑	↑	↑	Nl	The severity of bleeding related to the degree of factor V deficiency
	Factor VII deficiency			Easy bruising Mucosal bleeding Postoperative bleeding Menorrhagia Soft tissue hematomas Thrombosis				+	+	+	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		Eeasy bruising Inadequate clotting in trauma or mild injury Spontaneous hemorrhage Hemarthrosis Epistaxis Gingival bleeding	−	−	−	+	+	+	Nl	Nl	Nl	↑	Nl	−
		Type B deficiency		Neonatal bleeding Trauma-related soft tissue hemorrhage Hemarthrosis Hematomas	−	−	−	+	+	+	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			Trauma Burn Crush injury Sepsis Malignancy Obstetric complication: abruption, amniotic fluid embolism Hemolytic anemia	+	+	+	+	+	+	↓	↑	↑	↑	Nl	−
	Vitamin K Deficiency			Bleeding after trauma Epistaxis Hematoma Gastrointestinal bleeding Menorrhagia Hematuria Gum bleeding Oozing from venipuncture sites Easy bruisability	+	−	+	+	+	+	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.
• 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.

Natural History, Complications, and Prognosis

• If left untreated, patients with Wiscott-Aldrich syndrome may progress to develop manifestations associated with thrombocytopenia, and abnormal platelet function, 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.
• 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.
  • Bleeding diathesis (eg, epistaxis, ecchymoses, petechiae, hematemesis, intracranial and gastrointestinal hemorrhages)
  • 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.
  • Increased risk of malignancy such as lymphoma, leukaemia is a frequent occurence in Wiskott-Aldrich syndrome.
• 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%.

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, eczema, recurrent infections and the presence of congenital thrombocytopenia(< 70 000/mm3) with small platelet volume <5·0fl (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.

History and Symptoms

• Patients with Wiskott-Aldrich syndrome have

• 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:
  • 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.
  • Immunologic studies may show following findings:
    • 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.

MRI

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

Treatment

Medical Therapy

• Mainstay therapy for Wiskott-Aldrich syndrome is conservative therapy and supportive care, which includes:
  • Prophylactic antimicrobial agents should be given to treat bacterial, viral, fungal and opportunistic infections.
    • Trimethoprim/sulfamethoxazole: 5mg/kg/day can be given to treat most bacterial and pneumocystis jirovecii pneumonia.
    • Acyclovir: 200mg/twice daily may be given to treat viral infections (eg, HSV-1)
    • Fluconazole: 3mg/kg/day may be given to treat fungal infections.
  • Platelet transfusions:
    • Platelet transfusions can be given to treat bleeding episodes such as life-threatening gastrointestinal and intracranial hemorrhages. Platelet transfusions can also be given to patients who are undergoing any surgical procedure.
    • If a patient can be chosen for transfusion, platelets and blood products should be irradiated and must be obtained from a CMV free donor.
  • Intravenous immunoglobulins:
    • Preferred regimen: 400 to 600 mg/kg can be given every three weeks
  • Immunosuppressive agents: Rituximab can be given to treat autoimmune cytopenias such as hemolytic anemia, neutropenia, associated with Wiskott- Aldrich syndrome.
  • Thrombopoietic agents: Eltrombopag may be helpful in increasing platelet count in patients with Wiskott-Aldrich syndrome but it may not improve platelet surface activation.
  • Gene therapy: Gene therapy is an alternative curative treatment for Wiskott-Aldrich syndrome, which is still going under trials.

Surgery

• Hematopoietic stem cell transplantation (HSCT):
  • HSCT is the only standard curative treatment for Wiskott-Aldrich syndrome.
• 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.

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 in decreaing the occurance .

Secondary Prevention

• There are no established measures for the secondary prevention of the Wiskott-Aldrich syndrome.

References

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