Chediak-Higashi Syndrome

The Chediak-Higashi Syndrome (CHS) is a hereditary disease. Due to an immunodeficiency, the gene abnormality is associated with recurrent infections, peripheral neuropathy and partial albinism. The life expectancy of those affected is greatly reduced. There is an opportunity for therapy through bone marrow transplantation.

What is Chediak Higashi Syndrome?

Chediak-Hygashi syndrome is a very rare autosomal recessive disorder. It is created by mutating a lysosomal regulatory protein, which causes a decrease in phagocytosis. This decline leads to recurrent purulent infections, partial albinism and peripheral neuropathy. It occurs in humans, farm animals, Persians, rats, mice, minks, foxes and the only captured albino killer whale.

causes

Genetic diseases are determined by the combination of parental genes for a certain trait. CHS is a recessive inherited condition. The individual inherits the syndrome when 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.

You will not experience symptoms. Mutations in the CHS1 gene (also: LYST) have been linked to the Chediak-Higashi syndrome. This gene contains instructions for making a protein that regulates lysosomal traffic. Scientists believe that this protein plays a role in transporting materials into the lysosomes.

The movements of proteins within the cells are impaired or incorrectly addressed by the mutated gene. Lysosomes act as recycling centers for cells. They use digestive enzymes to break down toxic substances. They digest bacteria that invade the cell and recycle worn cell components.

Defects in the transport of white blood cells into the cells prevent the killing of pathogens such as viruses and bacteria. An immune deficiency develops. A granulate in which the skin pigment melanin is produced is disrupted. In this case, the pigment cannot be transported into the appropriate skin cell.

LYST (lysosomal trafficking regulator) is involved in the normal function of the lysosomes. The exact role of the gene is unknown. The risk of illness in the child is 25 percent if both parents are carriers of the genetic defect. Gender does not play a role in the likelihood of getting sick.

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Symptoms, ailments & signs

People with CHS have light skin and silvery hair. In most cases, they suffer from sensitivity to the sun and photophobia. While other signs and symptoms occur occasionally, infections and neuropathies are common side effects. The mucous membranes, skin and airways are affected by infections.

Sick children are susceptible to infections from gram-positive and gram-negative bacteria and fungi. Staphylococci are the most common cause of infection. Neuropathies often start in teenagers and develop into the most distinctive problem. Infections in CHS patients tend to be severe to life-threatening. Few patients with this disease experience adulthood.

Most children with Chediak-Higashi syndrome reach a stage known as the "accelerated phase" or "lymphoma-like syndrome". In the accelerated phase, defective white blood cells divide in an uncontrolled manner and invade the body's own organs. The accelerated phase is accompanied by fever, episodes of abnormal bleeding, excessive infections and organ failure. These medical problems are usually life threatening.

Diagnosis & course

The diagnosis can be confirmed with bone marrow smears. Plasma inclusion bodies are visible in the myeloid cells in the bone marrow. CHS can be diagnosed prenatally by examining hair samples from a fetal scalp biopsy. It can also be detected by testing leukocytes from a fetal blood sample.

Neutropenia is the most common clinical manifestation of Chediak-Higashi syndrome. The syndrome is associated with ocular albinism. Patients are prone to infections, especially staph and streptococci. CHS causes periodontal disease of the primary dentition. Other associated features include abnormalities in melanocytes, nerve defects, and circulatory disorders.

The symptoms of certain medical conditions can be similar to 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 in platelets and white blood cells.

The rare Hermansky-Pudlak syndrome manifests itself as decreased skin, hair and eye pigmentation. Unlike CHS, it impairs the functions of the lungs, intestines, kidneys and heart through fatty deposits.

Complications

In most cases, Chediak-Higashi syndrome greatly reduces life expectancy. Without treatment, death can occur relatively quickly. Most patients are very sensitive to light and also suffer from photophobia and albinism.

Strong infections often occur that would not cause disease in a healthy person. The infections mainly affect the respiratory tract and the mucous membranes, which can lead to inflammation. Children in particular are very susceptible to various infections.

In severe cases, there will be a severe fever and internal bleeding from 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, a bone marrow transplant is mainly performed.

After the transplant, the patient is given strong antibiotics and drugs that strengthen the immune system. This can bring life expectancy back to normal. With successful treatment, everyday life is no longer restricted. However, the affected person still has to protect himself from direct sunlight. This is done with the help of sunscreen and sunglasses. If these protective measures are observed, there are no further complications.

When should you go to the doctor?

The symptoms of Chediak-Higashi syndrome are usually recognized immediately after birth. For this reason, an additional diagnosis is no longer necessary. However, you should still see a doctor regularly to check your skin.

A visit to the doctor is also necessary if the high sensitivity to light causes burns or other damage to the skin. An examination is also useful in the case of frequent infections or complaints of the respiratory tract and can help avoid 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 especially advisable if the fever persists. The treatment of the disease is carried out by the respective specialist and depends heavily on the severity of the symptoms. Unfortunately, a complete cure is not possible, so that the patients usually also suffer from a significantly reduced life expectancy.

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Treatment & Therapy

There is no specific method for treating Chediak-Higashi syndrome. Approaches vary depending on the stage of the disease at diagnosis. The causal transplantation of bone marrow was successful in many patients. The transplant is promising if it is carried out before the development of the accelerated phase.

The transfer corrects immune and circulatory disorders and prevents the accelerated phase from occurring. If the disease is in the accelerated phase, remission from hemophagocytosis must be achieved before a bone marrow transplant. Infections are treated with antibiotics, abscesses are drained. DDAVP can be given to prevent excessive bleeding.

Further treatments for CHS are symptomatic. Bacterial infections and fungal infections are treated with antibiotics and antimycotics. In the final stages of the disease, antiviral drugs such as acyclovir were tested. The immunomodulating and immunosuppressive agents prednisone and cyclophosphamide have been tried.

If bleeding heavily after injury or surgery, platelet transfusions may be necessary. Vitamin C therapy has improved immune function and blood clotting in some patients. People with CHS should minimize unprotected solar radiation. If an affected person is exposed to sunlight, sunglasses and sunscreen are helpful for the skin.

Outlook & forecast

A complete cure cannot be achieved in Chediak-Higashi syndrome because it is a genetic disease. For this reason, the symptoms can only be alleviated to a very limited extent. The life expectancy of those affected is also significantly reduced by Chediak-Higashi syndrome.

The only way to limit the disease is through bone marrow transplantation. As a rule, the transplant only makes sense if it takes place before the accelerated phase of the disease. After this phase, no further treatment is possible. Although the therapy delays the onset of the symptoms, it does not achieve a complete cure.

The severe skin complaints often lead to psychological complaints or severe depression. Having vaccinations can prevent various diseases and thereby increase the life expectancy of the patient. The psychological complaints due to Chediak-Higashi syndrome often occur in early childhood, as the children have to be isolated from other children due to the disease.

In severe cases, the syndrome is treated with a spinal cord transplant. However, even here there is only a short-term improvement and not a complete treatment of the disease.

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prevention

Due to 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 offer for people with genetic disorders.

Aftercare

Follow-up care measures are severely limited in Chediak-Higashi syndrome and in many cases not even possible. Those affected by this disease are primarily dependent on an early diagnosis in order to identify the disease early and initiate treatment. If you wish to have children, genetic counseling is very advisable so that the Chediak-Higashi syndrome is not passed on to the children.

A complete cure is not possible either, since this disease is a genetic disease. In many cases, those affected are dependent on taking antibiotics and other medication. It is always important to ensure the correct dosage with regular intake. Antibiotics should never be taken together with alcohol, otherwise their effect will be significantly weakened.

In addition, if you have any questions or questions, you should always consult a doctor first. Those affected should also protect themselves from direct sunlight with Chediak-Higashi syndrome. Sunscreen should always be applied, although the eyes can be protected even with sunglasses. Whether the syndrome will lead to a reduced life expectancy cannot generally be predicted.

You can do that yourself

Chediak-Higashi syndrome is a rare hereditary disease. Those affected cannot take self-help measures to combat the cause of the disease. Couples who have had the syndrome in their families should seek genetic counseling. As part of such advice, you will learn how great the risk is that your offspring will actually fall ill and what stress they will have to face in this case.

For people with Chediak-Higashi syndrome, otherwise harmless diseases are often life-threatening. In the case of children, you should therefore clarify with the attending physician which vaccinations against the usual childhood diseases make sense. It may also be necessary to isolate children from their peers. The latter is often very stressful for those affected. Parents should therefore consult a therapist at an early stage who will ensure professional psychological care for the child.

Since the patients usually become ill shortly after birth, parents should insist that their children be looked after by a competent doctor who actually already has experience with the rare disease. The most effective treatment for severe forms of Chediak-Higashi syndrome is with a spinal cord transplant. In severe cases, the possibility of a spinal cord transplant should be clarified at an early stage.