Wiskott-Aldrich syndrome is an inherited genetic defect that, to date, can only be cured by bone marrow transplantation. With an incidence of about 1:250,000, the disease is rare, affecting only boys as a result of X-linked recessive inheritance.
What is Wiskott-Aldrich syndrome?
Wiskott-Aldrich syndrome is the name given to a rare genetic immunodeficiency that is inherited in an X-linked recessive manner. Characteristic of the hereditary disease is a symptom triad consisting of recurrent severe infections due to a disturbed immune system, increased bleeding tendency with thrombocytopenia (reduced and functionally impaired platelet count) and eczema, whereby the individual clinic can vary greatly from affected person to affected person. As a rule, Wiskott-Aldrich syndrome manifests itself immediately after birth or in the neonatal period in the form of punctate skin bleeding (petechiae). In the further course, bloody diarrhea as well as a pronounced injury-related hemorrhage up to internal bleeding and cerebral hemorrhage may occur as a result of the coagulation disorder. In many cases, secondary autoimmune disorders are seen in Wiskott-Aldrich syndrome. In addition, there is an increased risk of malignant lymphoma.
Causes
Wiskott-Aldrich syndrome is due to a defect in a specific gene on the shorter arm of the X chromosome that encodes the defective protein (also known as WASP) responsible for the syndrome. The affected gene is significant for the proper functioning of the cytoskeleton, which plays an essential role in the synthesis of platelets from megakaryocytes (progenitor cells) and regulates communication or signaling between immune cells. On the one hand, the mutations result in a reduced number of platelets, which also have only a limited functionality, leading to an increased bleeding tendency with simultaneously disturbed blood coagulation. On the other hand, the gene alterations cause different defects on different immune cells, which lead to a disturbed signal exchange, a restricted function of T cells and/or impaired production of antibodies. As a result of the impaired immune system, repeated viral, bacterial, and mycotic infections manifest, which can have comparatively severe courses in Wiskott-Aldrich syndrome.
Symptoms, complaints, and signs
Wiskott – Aldrich syndrome is an immunodeficiency. It is characterized by skin rashes, a low platelet count, and recurrent infections. The symptoms are caused by a malfunction of white blood cells and platelets. This results in dyfunctionality of the immune system. The rashes are often confused with atopic dermatitis. The reason for this is the similarity to atopic eczema. However, in contrast to neurodermatitis, the eczema in the Wiskott – Aldrich symptom can appear in the first weeks of life. In some cases, the eczema is severe and may be accompanied by small skin hemorrhages (hemorrhagic eczema). In Wiskott – Aldrich symptom it happens that the treated and healed eczema reappears. Low platelet count can lead to autoimmune diseases. These are characterized by the decay of red blood cells (autoimmune hemolytic anemia), inflammation of small blood vessels in the skin or organs (vasculitis), decay of platelets (immune thrombocytopenia) or nephritis or colitis, i.e. inflammation of the kidneys or colon. Inflammation of the colon may be manifested by bloody or painful diarrhea. Last, there may be an increased susceptibility to infections. These conditions may include middle ear infections, sinus infections, or the like.
Diagnosis and course
Wiskott-Aldrich syndrome can usually be diagnosed on the basis of clinical symptoms (mainly petechiae, eczema, recurrent infections). The diagnosis is confirmed by further blood tests, in the course of which a lowered number and reduced size of the platelets can be determined. The antigen body level is also conspicuous (increased IgE, IgD and IgA concentrations with a reduced IgM value). In addition, older patients often have impaired T-lymphocyte function.In addition, the specific genetic defect on the WAS gene and thus the expected expression of Wiskott-Aldrich syndrome can already be determined during prenatal diagnostics. Wiskott-Aldrich syndrome has a good prognosis and high chances of cure with successful bone marrow transplantation. However, without transplantation, life expectancy is about 10 to 20 years. In addition, there is an increased risk of cancer in this case.
Complications
First and foremost, Wiskott-Aldrich syndrome results in very severe bleeding under the skin. These can have a negative impact on the aesthetics of the affected person, causing many patients to feel ashamed and uncomfortable with the condition. Reduced self-esteem or inferiority complexes can also occur as a result of the syndrome. Furthermore, bleeding can also occur on the internal organs. The blood is then often excreted during bowel movements or urination, so that the affected person suffers from bloody bowel movements or bloody urine. Sometimes patients experience a panic attack. Furthermore, anemia sets in, which has a negative effect on the health of the affected person. There is permanent fatigue and exhaustion. The susceptibility to infections also increases and the immune system of the affected person is considerably weakened by Wiskott-Aldrich syndrome. Treatment of Wiskott-Aldrich syndrome is usually always based on the individual symptoms. These can be limited with the help of medication, whereby complications do not occur. Skin complaints can be limited with the help of creams or ointments. As a rule, the life expectancy of the patient is not negatively affected by the disease.
When should one go to the doctor?
Immediately after birth, the obstetric team present checks the health of the mother as well as that of the newborn. Irregularities and abnormalities are documented and, if necessary, further medical tests are ordered. Under optimal conditions, health peculiarities are already noticed and diagnosed at this stage. Parents or relatives therefore do not need to make any further efforts. However, if health discrepancies become apparent as the child continues to develop, a physician should be consulted. If there is bleeding or discoloration of the skin, there is already cause for concern. If blood is noticed in the child’s excretions, a physician should be consulted immediately. If the infant shows behavioral abnormalities, a strong restlessness or disturbances in the functioning of the organism, a visit to the doctor is necessary. In case of rashes on the skin, abnormalities of the movements as well as an increased body temperature, a medical examination is necessary. For a diagnosis, the complaints should be discussed with a doctor. Peculiarities of eating behavior, sleep disorders as well as irregularities of reaction should also be clarified by a doctor. Eczema as well as the development of edema on the body are indications of a present disease. If persistent or suddenly recurring diarrhea is observed in the further growth process of the child and the child complains of pain in the abdomen, he needs medical help.
Treatment and therapy
Therapeutic measures in Wiskott-Aldrich syndrome are aimed, first, at eliminating the cause as part of a causal therapy and, second, at treating the symptoms depending on the specific impairments present. Thus, infectious diseases in patients affected by Wiskott-Aldrich syndrome should be treated early and consistently with antibiotics. If necessary, prophylactic antibiotic therapy is useful. If the synthesis of antibodies is disturbed, a subcutaneous or intravenous supply of immunoglobulins is recommended. Thrombocytopenia can be treated by drug therapy with cortisone or high-dose immunoglobulins. In addition, splenectomy (surgical removal of the spleen) may be considered to improve thrombocytopenia. Transfused platelet concentrates may be indicated for life-threatening conditions resulting from marked bleeding. Lipid-replenishing creams and ointments as well as short-term cortisone-containing creams and ointments are used to minimize eczematous skin lesions. Dietary measures such as avoidance of foods containing egg and cow’s milk can support the therapy of eczema.Causal therapy for Wiskott-Aldrich syndrome is bone marrow transplantation, in which the body’s own bone marrow is chemotherapeutically destroyed and subsequently replaced by healthy infused bone marrow. The best results can be achieved with early intervention (before the age of five). Gene or gene replacement therapy represents another causal treatment for Wiskott-Aldrich syndrome, although this is still undergoing clinical testing.
Prevention
Because Wiskott-Aldrich syndrome is a genetic disorder, it cannot be prevented to date. Death vaccines are recommended to prevent infections that can take a severe course, while live vaccines such as those for mumps, measles, rotavirus, or chickenpox should be avoided in the presence of Wiskott-Aldrich syndrome.
Follow-up
Wiskott-Aldrich syndrome is a hereditary disease that, to date, has no causative treatment. Only a few studies have tested causal treatment, but for most patients this option is not an option because of the risks. During follow-up, the course of the symptoms is checked in order to initiate further measures. Regular check-ups are necessary when drugs such as cotrimoxazole or penicillin V are administered. If any of the symptoms have been cured, the physician must regularly check the patient’s health status following recovery to minimize the risk of severe internal bleeding and other complications. After an infection, the patient must first spend a few days in the hospital. After that, follow-up care is necessary. Follow-up care for Wiskott-Aldrich syndrome is provided by the appropriate internist or other specialist. Several follow-up visits are usually indicated after an infection. Depending on the severity of the infection, prolonged hospitalization may be necessary. Accompanying therapeutic support for patients may also be necessary. Psychological help is particularly useful because of the poor prognosis that most often accompanies Wiskott-Aldrich syndrome.
Here’s what you can do yourself
Wiskott-Aldrich syndrome first requires medical diagnosis and treatment. Therapy of the condition can be supported at home by various measures. First of all, it is important to observe the sick child well. If typical symptoms such as painful eczema appear, the doctor must be informed immediately. Infections are usually treated by means of topical or systemic steroids. The most important self-help measure is to observe the sufferer and to inform the physician in case of side effects or interactions. Wiskott-Aldrich syndrome can take a variety of courses, about which relatives should be carefully aware. Somewhat older children should be educated about their condition. The physician can provide key informational materials and points of contact. This, together with comprehensive concomitant medical therapy, will enable patients to live relatively symptom-free lives. Regular research regarding new forms of therapy is also important. With regard to Wiskott-Aldrich syndrome, gene therapies are currently being tested which could prove effective in a few years. Patients can participate in testing programs or focus on symptomatic treatment. Which self-help measures are appropriate will be discussed with the appropriate specialist.
