Chediak-Higashi syndrome (CHS) is an inherited disorder. Due to an immunodeficiency, the gene abnormality is associated with recurrent infections, peripheral neuropathy, and partial albinism. The life expectancy of affected individuals is greatly reduced. Bone marrow transplantation offers a chance of therapy.
What is Chediak-Higashi syndrome?
Chediak-Hygashi syndrome is a very rare autosomal recessive inherited disorder. It results from mutation of a lysosomal regulatory protein, causing a decrease in phagocytosis. This decrease leads to recurrent purulent infections, partial albinism, and peripheral neuropathy. It occurs in humans, farm animals, Persian cats, rats, mice, minks, foxes, and the only albino killer whale captured.
Causes
Genetic diseases are determined by the combination of parental genes for a particular trait. CHS is a recessively inherited disorder. The individual inherits the syndrome if the gene in question is present in both parents with an abnormality. The phenotype does not appear in every generation. Individuals with one normal and one abnormal gene are carriers of the disease. Symptoms do not occur in them. Mutations in the gene CHS1 (also: LYST) have been linked to Chediak-Higashi syndrome. This gene contains instructions for making a protein that regulates lysosomal traffic. Scientists hypothesize that this protein plays a role in transporting materials into lysosomes. The movement of proteins within cells is affected or misaddressed by the mutated gene. Lysosomes act as recycling centers of cells. They use digestive enzymes to break down toxic substances. They digest bacteria that enter the cell and recycle worn-out cell components. Defects in the transport of white blood cells into the cells prevents the killing of pathogens such as viruses and bacteria. Immune deficiency develops. A granule in which the skin pigment melanin is produced is disrupted. In this case, the pigment cannot be transported to the appropriate skin cell. LYST (lysosomal trafficking regulator) is involved in the normal function of lysosomes. The exact role of the gene is unknown. The risk of the child developing the disease is 25 percent if both parents are carriers of the gene defect. Gender does not play a role in the likelihood of developing the disease.
Symptoms, complaints, and signs
People with CHS have fair skin and silvery hair. In most cases, they suffer from sun sensitivity and photophobia. While other signs and symptoms tend to occur on a case-by-case basis, infections and neuropathies are common associated symptoms. Infections affect mucous membranes, skin, and respiratory tract. Sick children are susceptible to infections caused by Gram-positive and Gram-negative bacteria and fungi. Staphylococci are the most common cause of infection. Neuropathies often begin in the teen years and become the most prominent problem. Infections in CHS patients tend to be severe to life-threatening. Few patients with this disease live to adulthood. Most children with Chediak-Higashi syndrome reach a stage called the “accelerated phase” or “lymphoma-like syndrome.” In the accelerated phase, defective white blood cells divide uncontrollably and invade organs in the body. The accelerated phase is accompanied by fever, episodes of abnormal bleeding, exuberant infections, and organ failure. These medical problems are usually life-threatening.
Diagnosis and course
The diagnosis can be confirmed by bone marrow smears. Plasmic inclusion bodies become visible in myeloid cells in the bone marrow. Prenatally, CHS can be diagnosed by testing hair samples from a fetal scalp biopsy. Detection can also be made by testing leukocytes from a fetal blood sample. Neutropenia is the most common manifestation of Chediak-Higashi syndrome documented in clinical findings. The syndrome is associated with ocular albinism. Patients are susceptible to infections, especially staphylococci and streptococci. CHS causes periodontitis of the primary dentition. Other associated features include abnormalities in melanocytes, nerve defects, and circulatory disorders. Symptoms of certain conditions may resemble those of Chediak-Higashi syndrome.Griscelli syndrome is a hereditary disease also known as Chediak-Higashi-like syndrome. It is characterized by partial albinism and abnormalities of platelets and white blood cells. The rare Hermansky-Pudlak syndrome is manifested by decreased skin, hair, and eye pigmentation. Unlike CHS, it affects the functions of the lungs, intestines, kidneys, and heart due to fatty deposits.
Complications
In most cases, life expectancy is greatly reduced by Chediak-Higashi syndrome. Without treatment, death can occur relatively quickly. In this case, most patients are severely photosensitive and also suffer from photophobia and albinism. Often there are also severe infections that would not cause disease in a healthy person. The infections mainly affect the respiratory tract and the mucous membranes, so that inflammation can occur there. Children in particular are highly susceptible to various infections. In severe cases, there is a high fever and internal bleeding due to the infections. In the worst case, the bleeding can lead to organ failure if no treatment is used. The patient then usually dies. Since no specific treatment of the syndrome is possible, bone marrow transplantation is the main treatment. After the transplant, the patient receives strong antibiotics and drugs that strengthen the immune system. As a result, life expectancy can be returned to normal. If the treatment is successful, everyday life is no longer restricted. However, the affected person must still protect himself from direct sunlight. This is done with the help of sunscreen and sunglasses. If these protective measures are adhered to, there are no further complications.
When should you go to the doctor?
Usually, the symptoms of Chediak-Higashi syndrome are recognized immediately after birth. For this reason, an additional diagnosis is no longer necessary. However, a doctor should still be visited regularly to check the skin. A visit to the doctor is also necessary if burns or other damage to the skin occurs due to the high sensitivity to light. An examination is also useful in the case of frequent infections or complaints of the respiratory tract and can help to prevent various complications. Teenagers in particular are affected by the infections and need regular examination by a doctor. Since the disease eventually leads to organ failure, the organs should also be checked regularly by an internist. An examination is particularly advisable in the case of prolonged fever. The treatment of the disease is carried out by the respective specialists and depends strongly on the severity of the symptoms. Unfortunately, a complete cure is not possible, so that patients usually also suffer from a significantly reduced life expectancy.
Treatment and therapy
No specific method exists for the treatment of Chediak-Higashi syndrome. Approaches vary depending on the stage of the disease at diagnosis. Causal bone marrow transplantation has been successful in many patients. Transplantation is promising if performed before development of the accelerated phase. The transplant corrects immune as well as circulatory disorders and prevents the onset of the accelerated phase. If the disease is in the stage of accelerated phase, remission of hemophagocytosis must be achieved before bone marrow transplantation. Infections are treated with antibiotics, and abscesses are drained. DDAVP may be administered to prevent excessive bleeding. Other treatments for CHS are symptomatic. Bacterial infections and fungal infections are treated with antibiotics and antifungals. In the terminal phase of the disease, antiviral drugs such as aciclovir have been tested. The immunomodulatory and immunosuppressive agents prednisone and cyclophosphamide, respectively, have been tried. Platelet transfusions may be necessary in cases of severe bleeding after injury or surgery. Vitamin C therapy has been shown to improve immune function and blood clotting in some patients. CHS sufferers should minimize unprotected sun exposure. If an affected person is exposed to sunlight, sunglasses and sunscreen for the skin are helpful.
Outlook and prognosis
A complete cure cannot be achieved for Chediak-Higashi syndrome because it is a genetic disorder.For this reason, the symptoms can only be relieved to a very limited extent. The life expectancy of the affected person is also considerably reduced by Chediak-Higashi syndrome. The disease can only be limited by bone marrow transplantation. As a rule, transplantation is useful only if it takes place before the accelerated phase of the disease. After this phase, no treatment is possible. Although the therapy delays the onset of the symptoms, a complete cure is not achieved. Due to the severe skin discomfort, psychological discomfort or severe depression is also common. Various diseases can be prevented by vaccinations and thus the life expectancy of the patient can be increased. Often, the psychological complaints due to Chediak-Higashi syndrome occur in early childhood, as the disease requires the children to be isolated from other children. In severe cases, the syndrome is treated by transplantation of the spinal cord. However, even in this case, there is only a short-term improvement and not a complete treatment of the disease.
Prevention
Because of the genetic predisposition, only symptoms of Chediak-Higashi syndrome can be prevented. Antibiotics are used to prevent dangerous infections. Human genetic counseling is a medical service for people with genetic disorders.
Follow-up
Measures of follow-up care are severely limited in Chediak-Higashi syndrome and in many cases are not possible at all. Yet, affected individuals with this disease are primarily dependent on early diagnosis to detect the disease early and initiate treatment. If there is a desire to have children, genetic counseling is highly advisable to ensure that Chediak-Higashi syndrome is not inherited by the children. A complete cure is not possible either, as this is a genetic disease. Affected persons are in many cases dependent on taking antibiotics and other medications. Care must always be taken to ensure that the correct dosage is taken regularly. Antibiotics should never be taken together with alcohol, otherwise their effect is significantly weakened. Furthermore, a doctor should always be consulted first if there is any uncertainty or if there are any questions. Those affected by Chediak-Higashi syndrome should also protect themselves from direct sunlight. Sunscreen should always be applied, and the eyes themselves can be protected with sunglasses. It cannot be generally predicted whether the syndrome will result in a decreased life expectancy.
What you can do yourself
Chediak-Higashi syndrome is a rare inherited disorder. Affected individuals cannot take self-help measures to combat the disease causally. Couples whose families have had the syndrome should seek genetic counseling. During such counseling, they will learn how great the risk is that their offspring will actually contract the disease and what burdens they will face in this case. For those affected by Chediak-Higashi syndrome, otherwise harmless diseases are often life-threatening. In the case of children, it should therefore be clarified with the attending physician which vaccinations against the usual childhood diseases are useful. If necessary, it may also be necessary to isolate children from their peers. The latter is often emotionally very stressful for those affected. Parents should therefore consult a therapist at an early stage to ensure professional psychological care for the child. Since patients usually become ill shortly after birth, parents should insist that their children be cared for by a competent physician who actually has experience with the rare disease. The most effective treatment for severe forms of Chediak-Higashi syndrome is spinal cord transplantation. In severe courses, the possibility of a spinal cord transplant should be clarified at an early stage.
