Track topics on Twitter Track topics that are important to you
This study will investigate the underlying cause of Chediak-Higashi syndrome (CHS)-a rare inherited disease-and define the full spectrum of medical complications associated with it. It will study the LYST gene - the gene responsible for classic CHS-and investigate other genes that may cause milder forms of the syndrome.
Patients with CHS have a range of medical problems, including decreased pigment in the skin and eyes, a tendency toward bleeding because of a platelet dysfunction and recurrent infections due to white cell abnormalities. Some patients also have neurologic problems, such as poor sensation in the arms and legs. The only cure for CHS is bone marrow transplantation, but other measures can be taken, such as avoiding aspirin to prevent bleeding episodes.
Patients one month or older with decreased pigmentation and either a bleeding abnormality or history of excessive childhood infections may be eligible for this study, which is expected to continue for 5 to 10 years. Participants will be admitted to the NIH Clinical Center for about 5 days every 1 to 3 years, depending on the severity of their conditions, for the following procedures:
1. Medical history, physical examination, complete eye examination and consultations with infectious disease and neurology specialists
2. Blood tests, including routine tests, such as complete blood count, blood chemistries, etc.; tests to look for giant granules and platelet dense bodies; tests to examine white blood cell function; and tests to analyze DNA of the LYST gene
3. 24-hour urine collection to assess kidney function
4. Skin biopsy to study cells called fibroblasts, in which an area of skin is numbed with an anesthetic and a circular area 4 mm in diameter is then removed using a sharp punch and scissors. The wound is then dressed; healing time is usually within a week.
5. Visual evoked response test, in which small electrodes are applied to the scalp (similar to an electroencephalogram). The patient looks at a screen with changing patterns and at flashes of light while the electrical activity of the brain is recorded.
Depending on the individual patient's condition, consultations may also be arranged with hematology (blood), dermatology (skin) and pulmonology (lungs). Additional tests may include X-rays, computerized tomography (CT) or magnetic resonance imaging (MRI) of the head, pulmonary function tests to measure breathing capacity, and photographs of the face and body taken with underwear on.
Chediak-Higashi syndrome (CHS) is a rare autosomal recessive disorder characterized in its classical form by oculocutaneous albinism, a bleeding diathesis, recurrent infection due to abnormal neutrophil and natural killer cell function, and eventual progression to a lymphohistiocytic infiltration known as the "accelerated phase". Death often occurs within the first decade as a result of bleeding, infection, or development of the accelerated phase; bone marrow transplantation is curative except for the late occurrence of neurological deterioration. The basic defect is unknown, although it probably involves abnormal fusion or trafficking of intracellular vesicles. Patients with classical CHS have their disease due to mutations in the LYST gene, but mildly affected individuals have been reported whose genetic defect has not been defined. It is likely that these variants of CHS have abnormalities in proteins involved in the pathways responsible for vesicle fusion. Since the full clinical spectrum of CHS and its variants has not been characterized, and the underlying defects remain enigmatic, we plan to evaluate this group of patients clinically, biochemically, and molecularly, and perform cell biological studies on their fibroblasts, melanocytes, and transformed lymphoblasts. Routine admissions will be 5 days and occur every two years.
Chediak Higashi Syndrome
National Institutes of Health Clinical Center, 9000 Rockville Pike
National Institutes of Health Clinical Center (CC)
Published on BioPortfolio: 2014-08-27T03:57:37-0400
OBJECTIVES: I. Determine the efficacy of unrelated donor hematopoietic stem cell transplantation in the treatment of patients with life threatening hemophagocytic disorders. II. Determi...
This study will try to determine what causes learning, behavioral and emotional problems in children with chronic granulomatous disease (GCD) and other phagocyte disorders. (Phagocytes are...
This study will: 1) determine the biochemical and genetic causes of inherited immune diseases affecting phagocytes (white blood cells that defend against bacterial and fungal infections); ...
The aim of this study is to assess the frequency of metabolic syndrome in Down syndrome patients because the prevalence of diabetes mellitus and obesity is higher in individuals with Down ...
To evaluate the prevalence of metabolic syndrome in HIV-infected patients with previous evaluation of lipodystrophy syndrome, according to the severity of fat accumulation and antiretrovir...
To explore the genetic basis for a pedigree affected with Chediak-Higashi syndrome (CHS).
Chediak-Higashi syndrome (CHS) belongs to a group of partial oculocutaneous albinism and immunodeficiency. Five autosomal recessive conditions are recognized in this group, characterized by hypopigmen...
The neurobeachin-like 2 protein (Nbeal2) belongs to the family of beige and Chediak-Higashi (BEACH) domain proteins. Loss-of-function mutations in the human NBEAL2 gene or Nbeal2 deficiency in mice ca...
Kounis syndrome encompasses concepts including angina and allergic infarction described in relation to exposure to different allergens. The aim of this article is to describe a case of Kounis Syndrome...
A form of phagocyte bactericidal dysfunction characterized by unusual oculocutaneous albinism, high incidence of lymphoreticular neoplasms, and recurrent pyogenic infections. In many cell types, abnormal lysosomes are present leading to defective pigment distribution and abnormal neutrophil functions. The disease is transmitted by autosomal recessive inheritance and a similar disorder occurs in the beige mouse, the Aleutian mink, and albino Hereford cattle.
Condition with a variable constellation of phenotypes due to deletion polymorphisms at chromosome location 22q11. It encompasses several syndromes with overlapping abnormalities including the DIGEORGE SYNDROME, VELOCARDIOFACIAL SYNDROME, and CONOTRUNCAL AMOMALY FACE SYNDROME. In addition, variable developmental problems and schizoid features are also associated with this syndrome. (From BMC Med Genet. 2009 Feb 25;10:16) Not all deletions at 22q11 result in the 22q11deletion syndrome.
Rare congenital disorder with multiple anomalies including: characteristic dysmorphic craniofacial features, musculoskeletal abnormalities, neurocognitive delay, and high prevalence of cancer. Germline mutations in H-Ras protein can cause Costello syndrome. Costello syndrome shows early phenotypic overlap with other disorders that involve MAP KINASE SIGNALING SYSTEM (e.g., NOONAN SYNDROME and cardiofaciocutaneous syndrome).
An autosomal dominant aneurysm with multisystem abnormalities caused by increased TGF-BETA signaling due to mutations in type I or II of TGF-BETA RECEPTOR. Additional craniofacial features include CLEFT PALATE; CRANIOSYNOSTOSIS; HYPERTELORISM; or bifid uvula. Phenotypes closely resemble MARFAN SYNDROME; Marfanoid craniosynostosis syndrome (Shprintzen-Goldberg syndrome); and EHLERS-DANLOS SYNDROME.
Birth defect that results in a partial or complete absence of the CORPUS CALLOSUM. It may be isolated or a part of a syndrome (e.g., AICARDI'S SYNDROME; ACROCALLOSAL SYNDROME; ANDERMANN SYNDROME; and HOLOPROSENCEPHALY). Clinical manifestations include neuromotor skill impairment and INTELLECTUAL DISABILITY of variable severity.
Bioinformatics is the application of computer software and hardware to the management of biological data to create useful information. Computers are used to gather, store, analyze and integrate biological and genetic information which can then be applied...
Acne Dermatology Eczema Psoriasis Wound Care Dermatology is the medical specialty concerned with the diagnosis and treatment of skin disorders (Oxford Medical Dictionary). As well as studying how the skin works, dermatology covers...
Ophthalmology is the branch of medicine that is devoted to the study and treatment of eye diseases. As well as mild visual defects correctable by lenses, ophthalmology is concerned with glaucoma, uveitis and other serious conditions affecting the eye, ...