Chediak-Higashi syndrome (CHS) is a rare, inherited, complex, immune disorder of childhood (usually) characterized by abnormally pale skin and eyes (oculocutaneous albinism). Because the patient's white blood cells (leukocytes) are profoundly affected, especially in their capacity to transport cellular proteins, immune disorders are common, along with an increased susceptibility to infections. In addition, CHS patients tend to bruise and bleed easily. Neurological deficits are also common.
CHS is transmitted as an autosomal recessive trait.
The symptoms of CHS are apparent during early infancy. The hair is typically blond or light brown with a silvery tint. Affected children may be abnormally sensitivity to light (photosensitivity) and exhibit rapid, involuntary, eye movements (nystagmus).
More important and more serious are the affects of CHS on the patient’s immune and nervous systems.
Symptoms involving the nervous system include an unsteady posture and walk (ataxia) and lack of sensation in the arms and legs (peripheral neuropathy), leading to obvious signs of physical weakness and disability. Symptoms involving the immune system include a predisposition to bruising and bleeding (bleeding diathesis), susceptibility to recurrent infections and a tendency to develop a lymphoma-like malignancy of the blood.
Children with Chediak-Higashi syndrome often have abnormally low levels of white blood cells (leukocytes) and platelets (thrombocytopenia) and may be susceptible to frequent bacterial and fungal infections of the skin, respiratory tract, and/or mucous membranes. These infections are frequently accompanied by abnormally high fever. Children with this disorder may bruise easily and tend to bleed excessively when injured. Organs of the body including the lungs, brain, kidneys, adrenal glands, and/or liver may have impaired function in some cases. Children with this disorder may be susceptible to cancers of the blood (leukemia) and lymphatic system (lymphoma).
Advanced symptoms of CHS may include general muscle weakness, poor growth, tingling or burning sensations in the arms and legs (peripheral neuropathy), the inability to coordinate movement (ataxia), skin ulcerations, an abnormally enlarged liver or spleen (hepatomegaly or splenomegaly), and/or enlarged lymph nodes (lymphadenopathy).
Chediak-Higashi syndrome is inherited as an autosomal recessive genetic trait. The responsible gene has been mapped to chromosomal locus 1q42.1-q42.2 and is known as CHS1.
The abnormal gene affects the “traffic patterns” of proteins within the cells. Proteins (or enzymes) that are meant to go from one part of the cell to another are either misdirected or fail to be transported.
For example, a granule in which the skin pigment (melanin) is made is interfered with so that the pigment cannot be transported to the appropriate skin cell. Similarly, a defect in the transport of part of a white blood cell (wbc) renders the cell helpless in killing infective agents like viruses or bacteria and causing the immune problems.
Chromosomes, which are present in the nucleus of human cells, carry the genetic information for each individual. Human body cells normally have 46 chromosomes. Pairs of human chromosomes are numbered from 1 through 22 and the sex chromosomes are designated X and Y. Males have one X and one Y chromosome and females have two X chromosomes. Each chromosome has a short arm designated “p” and a long arm designated “q”. Chromosomes are further sub-divided into many bands that are numbered. For example, “chromosome 1q42.1″ refers to band 42.1 on the long arm of chromosome 1. The numbered bands specify the location of the thousands of genes that are present on each chromosome.
Genetic diseases are determined by the combination of genes for a particular trait which are on the chromosomes received from the father and the mother.
Recessive genetic disorders occur when an individual inherits the same abnormal gene for the same trait from each parent. If an individual receives one normal gene and one gene for the disease, the person will be a carrier for the disease, but usually will not show symptoms. The risk for two carrier parents to both pass the defective gene and, therefore, have an affected child is 25% with each pregnancy. The risk to have a child who is a carrier like the parents is 50% with each pregnancy. The chance for a child to receive normal genes from both parents and be genetically normal for that particular trait is 25%. The risk is the same for males and females.
All individuals carry 4-5 abnormal genes. Parents who are close relatives (consanguineous) have a higher chance than unrelated parents to both carry the same abnormal gene, which increases the risk to have children with a recessive genetic disorder.
Chediak-Higashi syndrome is a very rare disorder that affects males and females in equal numbers. It is usually obvious at birth or shortly thereafter. There does not appear to be a higher risk for any particular ethnic or racial group.
The diagnosis of Chediak-Higashi syndrome is usually made on the basis of the presence of 'giant granules' in microscopic analysis of white blood cells and red blood cells. The diagnosis is confirmed by bone marrow smears that show 'giant inclusion bodies' in the cells that develop into white blood cells (leukocyte precursor cells).
CHS can be diagnosed in an unborn child (prenatally) by examining a sample of hair from a fetal scalp biopsy or testing white blood cells (leukocytes) from a fetal blood sample.
Treatment of Chediak-Higashi syndrome is symptomatic. When bacterial or fungal infections occur, they should be vigorously treated with antibiotic or antifungal drugs. Acute viral infections may be treated with the anti-viral drug acyclovir and prednisone. Transfusions of white blood cells (leukocytes) may also be useful in treating some infections. Whole blood transfusions may be necessary if bleeding becomes excessive after injury or surgery. If a blood cancer (lymphoma) develops, standard cancer therapy (i.e., vincristine) is indicated depending on the type and location of the malignancy.
People with Chediak-Higashi Syndrome should avoid exposure to sunlight as much as possible. When affected individuals are exposed to sunlight, sunglasses and creams which contain sunscreens applied to the skin can be helpful. Genetic counseling may be of benefit for people with Chediak- Higashi Syndrome and their families.
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For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
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Researchers are studying bone marrow transplantation from a compatible donor (allogenic) and non-compatible donors (non-allogenic) as a possible treatment for severe cases of Chediak-Higashi Syndrome. In this procedure patients receive high doses of chemotherapy, followed by radiation therapy. Then donor bone marrow cells are given intravenously to the patient. It is hoped that this procedure may lead to the improvement of the blood abnormalities and immune deficiencies associated with Chediak-Higashi Syndrome and other immune deficiency disorders such as Wiskott-Aldrich Syndrome. More study is needed to determine the long-term safety and effectiveness of bone marrow transplantation for the treatment of Chediak- Higashi Syndrome.
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