Symptoms of Wiskott-Aldrich Syndrome

The severity of the symptoms of the disease in patients with Wiskott-Aldrich syndrome varies from intermittent thrombocytopenia with minimal hemorrhagic manifestations to a severe disease with severe infectious and autoimmune syndromes. Thus, at the moment, there is no clear correlation between the severity of the disease and the type of mutation. The discrepancy between several groups of researchers can be explained by the lack of a clear classification of WAS and, as a result, researchers classify patients with similar disease severity in different ways. Tew, however, the majority of missense mutations in 2 exons are accompanied by mild disease, nonsense and CDS mutations lead to severe Wiskott-Aldrich syndrome.

Hemorrhagic syndrome

The average age of diagnosing Wiskott-Aldrich syndrome is 21 months according to the 1994 study, and 90% of patients have hemorrhagic syndrome at the time of diagnosis. Since thrombocytopenia is usually seen from birth, the disease can manifest with umbilical cord bleeding, as well as symptoms such as melena, epistaxis, hematuria, petechial rash, and life-threatening intracranial and gastrointestinal bleeding. In 1994, bleeding was noted as the leading cause of death in the Wiskott-Aldrich syndrome.

Patients with Wiskott-Aldrich syndrome are often diagnosed with idiopathic thrombocytopenic purpura (ITP), which significantly delays the formulation of the present diagnosis.

In some patients with Wiskott-Aldrich syndrome, thrombocytopenia and hemorrhagic manifestations are the only symptoms of the disease, and for many years, prior to identifying the gene responsible for the syndrome, these patients were referred to the X-linked thrombocytopenia group. With a more thorough examination, some of them managed to detect laboratory disorders of the immune response in the absence or minimal clinical manifestations of immunodeficiency.

Eczema or atopic dermatitis of varying severity is manifested, as a rule, in the first year of life and is often accompanied by local infection. In patients with mild WAS, eczema may be absent or light, transient.

Infectious manifestations

Most patients with Wiskott-Aldrich syndrome develop progressive signs of immunodeficiency with age. Due to violations of humoral and cellular immunity, frequent infections are often observed in patients with moderate or severe course of Wiskott-Aldrich syndrome, which are often found in the first six months of life. Of these, the most common inflammation of the middle ear (78%), sinusitis (24%) and pneumonia (45%). The same retrospective study showed that 24% of patients had sepsis, 7% had meningitis and GI infections in 13%. The most frequent pathogens are H. Influenzae, S. Pneumoniae, P. Carinii, C. Albicans. Less common are viral infections, which include chickenpox and herpetic infections. Fungal diseases are rare. In patients with a mild course of Wiskott-Aldrich syndrome, there may be no mention of frequent infections.

Autoimmune diseases

According to Sullivan, autoimmune disorders are observed in 40% of patients with Wiskott-Aldrich syndrome. The most common hemolytic anemia, vasculitis and kidney damage. Autoimmune disorders are characteristic of severe disease. Some patients develop more than one autoimmune disease. Often, patients with WAS develop immune thrombocytopenia, accompanied by an elevated level of platelet IgG. In patients with Wiskott-Aldrich syndrome who have a normal platelet level as a consequence of splenectomy, sometimes a repeated decrease in the number of platelets as a result of the secondary autoimmune process is observed.

Malignant neoplasms

Malignant neoplasms often develop in adults or adolescents with Wiskott-Aldrich syndrome, but may also occur in children. The average age of development of malignant neoplasms in patients with Wiskott-Aldrich syndrome is 9.5 years. Previously, patients with WAS older than 5 years had a tumor incidence of 18-20% on average. With increasing life expectancy of patients with Wiskott-Aldrich syndrome due to improved medical care, the proportion of patients developing tumors has increased. The majority of tumors have lymphoreticular origin, among them most often non-Hodgkin's lymphomas are found, however, as typical for childhood neuroblastoma, rhabdomyosarcoma, Ewing's sarcoma and others are absent. Lymphomas often have extranodal localization and are characterized by an unfavorable prognosis.

Laboratory Pathology

As mentioned above, the most constant manifestation of Wiskott-Aldrich syndrome is thrombocytopenia with a decrease in platelet count. Reduced volume of platelets is almost a unique symptom, allowing differential diagnosis with other thrombocytopenia. To determine the functional characteristics of platelets in a clinical laboratory is not recommended, since this study is complicated by a reduced volume of platelets in patients with WAS.

Immune disorders in the Wiskott-Aldrich syndrome include both the impairment of both the humoral and the cell link. Disturbances of T-cell immunity include, first of all, lymphopenia, which is observed in patients with WAS from an early age. In a greater degree, CD8 lymphocytes are reduced in patients. In addition, WAS patients have a decreased response to mitogens, a decrease in proliferation in response to stimulation with allogeneic cells and monoclonal antibodies to CD3, a delayed-type hypersensitivity reaction in response to specific antigens. Hypersensitivity reactions of delayed type are disrupted in 90% of patients. In the humoral unit there is a moderate decrease in B-pimphocytes, a decrease in IgM level, a normal or decreased IgG level, an increase in IgA and GdE. An interesting feature of the immune status of WAS patients is the relative and absolute increase in natural killers. There is evidence that this fact has pathogenetic significance.

Wiskott-Aldrich syndrome is also characterized by the inability of patients to synthesize antibodies to sex with isaharide antigens. For the first time this defect was described as the absence of isogenase in these patients. Later it was shown that patients with Wiskott-Aldrich Syndrome are unable to produce antibodies in response to antigens such as pneumococcal polysaccharides, lipopolysaccharide VI E. Coli Salmonella antigens.

Standard studies of the neutrophil and macrophage immunity units, including studies of neutrophil mobility, phagocytic response, granule release, revealed no abnormalities. There are reports of a violation of chemotaxis of neutrophils and monocytes.