Última actualización:
August 18, 2015
Años publicados: 1986, 1987, 1990, 1994, 1996, 2004, 2009, 2015
NORD gratefully acknowledges Sarah Tomer, Editorial Intern from the University of Notre Dame, and Wendy Introne, MD, Staff Clinician, National Human Genome Research Institute, for assistance in the preparation of this report.
Chediak-Higashi syndrome (CHS) is a rare, inherited, complex, immune disorder that usually occurs in childhood characterized by reduced pigment in the skin and eyes (oculocutaneous albinism), immune deficiency with an increased susceptibility to infections, and a tendency to bruise and bleed easily. Neurological deficits are also common. CHS is transmitted as an autosomal recessive genetic condition.
The symptoms of CHS may be apparent during early infancy. Hair is typically blond or light brown with a silvery tint. Affected children may be abnormally sensitive to light (photosensitivity) because of the reduced pigment in the eyes and skin, and may exhibit rapid, involuntary, eye movements (nystagmus). More important and more serious are the effects of CHS on the patient’s immune and nervous systems.
In CHS, white blood cells contain abnormal granules that are markedly enlarged. These granules can be seen by looking at the blood cells under the microscope, and if present, are diagnostic of CHS. These abnormal granules affect the ability of the white blood cells to fight infection. Children are susceptible to frequent bacterial, viral, and fungal infections, particularly of the skin and respiratory tract. Children with CHS can also have abnormally low levels of white blood cells. Children with this disorder may bruise easily or bleed excessively when injured. Platelet numbers are usually normal, but the platelets do not function properly causing easy bruising or prolonged bleeding.
The disease can be categorized into classic and atypical (mild) forms. Individuals with the atypical form may have fewer or less severe, infections and milder symptoms. Children with the classic form of the disease are at risk for developing the accelerated phase. The accelerated phase occurs in up to 85% of patients and can occur at any age. The accelerated phase is caused by an excess production of lymphocytes by the immune system. Patients can develop symptoms such as fever, swollen lymph nodes, enlargement of the liver and spleen, anemia, low WBC count, and low blood platelet count. This is a serious condition and needs to be treated right away.
Neurological symptoms occur in early adulthood. Symptoms involving the nervous system include an unsteady posture and walk (ataxia) and loss of sensation in the arms and legs (peripheral neuropathy).This can progress to physical weakness and disability. Some patients can have symptoms that resemble Parkinson’s disease.
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 LYST gene.
The abnormal gene affects the “traffic patterns” or movement of proteins within the cells. Proteins (or enzymes) that are meant to go from one part of the cell to another may be 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 within 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 an abnormal gene for the same trait from each parent. If an individual receives one normal gene and one abnormal 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 often obvious at birth or shortly thereafter. There does not appear to be a higher risk for any particular ethnic or racial group. There are less than 500 cases of the disease on record. 85% of affected individuals progress to the accelerated phase.
The diagnosis of CHS is usually made by the presence of ‘giant granules’ in microscopic analysis of white blood cells. ‘Giant inclusion bodies’ can also be seen in the cells that develop into white blood cells (leukocyte precursor cells) in the bone marrow.
Pigment clumping in hair that can be seen under light microscopy is another method for diagnosis that would be done if a blood smear showed enlarged granules.
Treatment
Management varies depending of the stage of the disease at the time of diagnosis. Ideally, bone marrow transplant should be performed before the patient develops the accelerated phase. Bone marrow transplant corrects the immune and bleeding abnormalities and prevents the development of the accelerated phase. If the accelerated phase occurs, hemophagocytosis must be in remission before a bone marrow transplant can occur. Those patients are given chemotherapy to get the accelerated phase into remission. Bone marrow transplant can occur after the patient is in remission. Before major procedures, a drug to prevent excessive bleeding, DDVAP, can be administered.
Other than these options, treatment of CHS 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 drugs. Platelet transfusions may be necessary if bleeding becomes excessive after injury or surgery.
People with CHS should minimize unprotected sun exposure. When affected individuals are exposed to sunlight, sunglasses and sunscreens applied to the skin can be helpful. Genetic counseling may be of benefit for people with CHS and their families.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov . All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Boxer LA. Chediak-Higashi Syndrome. In: NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:379.
Frank MM, Austen KF, Claman HN, et al. Eds. Samter’s Immunological Diseases. 5th ed. Little Brown and Company, Boston, MA; 1995:594-95.
REVIEW ARTICLES
Ward DM, Shiflett SL, Kaplan J. Chediak-Higashi syndrome: a clinical and molecular view of a rare lysosomal disorder. Curr Mol Med. 2002;2:469-77.
Shiflett SL, Kaplan J, Ward DM. Chediak-Higashi syndrome: a rare disorder of lysosomes and lysosome related organelles. Pigment Cell Res. 2002;15:251-57.
Huizing M, Anikster Y, Gahl WA. Hermansky-Pudlak syndrome and Chediak-Higashi syndrome: disorders of vesicle formation and trafficking. Thromb Haemost. 2001;86:233-45.
Ward DM, Griffiths GM, Stinchcombe JC, et al. Analysis of the lysosomal storage disease Chediak-Higashi syndrome. Traffic. 2000;1:816-22.
JOURNAL ARTICLES
Yamazaki S, Takahashi H, Fujii H, et al. Split chimerism after allogenic bone marrow transplantation in Chediak-Higashi syndrome. Bone Marrow Transplant. 2003;31:137-40.
Shome DK, Al-Mukharraq H, Mahdi N, et al. Clinicopathological aspects of Chediak-Higashi syndrome in the accelerated phase. Saudi Med J. 2002;23:464-66.
Karim MA, Suzuki K, Fukai K, et al. Apparent genotype-phenotype correlation in childhood, adolescent, and adult Chediak-Higashi syndrome. Am J Med Genet. 2002;108:16-22.
Trigg ME, Schugar R. Chediak-Higashi syndrome: hematopoietic chimerism corrects genetic defect. Bone Marrow Transplant. 2001;27:1211-13.
Delcourt-Debruyne EM, Boutigny HR, Hildebrand HF. Features of severe periodontal disease in a teenager with Chediak-Higashi syndrome. J Periodontol. 2000;71:816-24.
Fukuda M, Morimoto T, Ishida Y, et al. Improvement of peripheral neuropathy with oral prednisolone in Chediak-Higashi syndrome. Eur J Pediatr. 2000;159:300-01.
INTERNET
Introne WJ, Westbroek W, Golas GA, et al. Chediak-Higashi Syndrome. 2009 Mar 3 [Updated 2015 Jan 15]. In: Pagon RA, Adam MP, Ardinger HH, et al., editors. GeneReviews [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2015. Available from: https://www.ncbi.nlm.nih.gov/books/NBK5188/ Accessed June 16, 2015.
McKusick VA, Ed. Online Mendelian Inheritance in Man(OMIM). The Johns Hopkins University. Chediak-Higashi Syndrome; CHS. Entry Number; 214500: Available at https://omim.org/entry/214500 Last Edit Date 10/07/2013. Accessed June 16, 2015.
Brooks DG. Chediak-Higashi syndrome. In: Medical Encyclopedia. MEDLINEplus. Update Date 9/8/2013. www.nlm.nih.gov/medlineplus/ency/article/001312.htm Accessed June 16, 2015.
Nowicki R, Szarmach H. Chediak-Higashi Syndrome.Medscape. Updated: Mar 5, 2013. www.emedicine.com/derm/topic704.htm
Accessed June 16, 2015.
National Library of Medicine Genetics Home Reference. Chediak-Higashi syndrome. Reviewed January 2014. https://ghr.nlm.nih.gov/condition/chediak-higashi-syndrome . Accessed June 16, 2015.
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Aprende más https://rarediseases.org/patient-assistance-programs/caregiver-respite/The information provided on this page is for informational purposes only. The National Organization for Rare Disorders (NORD) does not endorse the information presented. The content has been gathered in partnership with the MONDO Disease Ontology. Please consult with a healthcare professional for medical advice and treatment.
The Genetic and Rare Diseases Information Center (GARD) has information and resources for patients, caregivers, and families that may be helpful before and after diagnosis of this condition. GARD is a program of the National Center for Advancing Translational Sciences (NCATS), part of the National Institutes of Health (NIH).
View reportOrphanet has a summary about this condition that may include information on the diagnosis, care, and treatment as well as other resources. Some of the information and resources are available in languages other than English. The summary may include medical terms, so we encourage you to share and discuss this information with your doctor. Orphanet is the French National Institute for Health and Medical Research and the Health Programme of the European Union.
View reportOnline Mendelian Inheritance In Man (OMIM) has a summary of published research about this condition and includes references from the medical literature. The summary contains medical and scientific terms, so we encourage you to share and discuss this information with your doctor. OMIM is authored and edited at the McKusick-Nathans Institute of Genetic Medicine, Johns Hopkins University School of Medicine.
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