Study of Chediak-Higashi Syndrome

NCT ID: NCT00005917

Last Updated: 2025-12-26

Basic Information

• Recruitment Status: RECRUITING
• Total Enrollment: 60 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2002-09-10

Brief Summary

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 infection or the 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 may occur every two years, or required by changes in clinical symptomatology.

Detailed Description

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 often progression to a lymphohistiocytic infiltration known as the accelerated phase . Death generally occurs within the first decade as a result of infection or the development of the accelerated phase; bone marrow transplantation is curative except for the late occurrence of neurological deterioration. However, our research has identified mildly affected individuals who present primarily with a neurological phenotype characterized by central and peripheral nervous system involvement. In addition, classical cases treated with bone marrow transplant (BMT) and surviving into adulthood usually develop neurological symptoms adding relevance to the study of pathophysiology of this disease outside of the hematological and immune systems. The only gene known to be associated with CHS is LYST; however, there are some patients with CHS in whom mutations have not been found, suggesting locus heterogeneity. A genotype-phenotype correlation had begun to emerge, but recent reports noted exceptions to this correlation. The basic defect is unknown, although it probably involves abnormal fusion or trafficking of intracellular vesicles. With regards to neurologic involvement, LYST likely also plays a role in neuronal axonal transport and neurotransmitter pools. We plan to evaluate individuals with CHS clinically, biochemically, and molecularly, and perform cell biological studies on their fibroblasts, melanocytes, and transformed lymphoblasts. Routine admissions may be 3-5 days and may occur every one to two years, or as required by changes in clinical symptomatology.

Conditions

Chediak-Higashi Syndrome

Keywords

Albinism; Giant Granules; Infection; Melanosomes; Platelet Storage Pool Defect; Natural History

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Study Groups

Chediak-Higashi Syndrome

Confirmed or suspected patients with Chediak-Higashi Syndrome.

No interventions assigned to this group

Eligibility Criteria

Inclusion Criteria

• ELIGIBILITY:

Patients will be between the age of 1 month and 70 years. All patients entering this study will have some degree of oculocutaneous albinism plus either a bleeding diathesis or a history of excessive infections in childhood. Objective evidence of a platelet storage pool deficiency (e.g., an abnormal secondary aggregation response or absent platelet dense bodies) or of a lysosomal fusion abnormality (e.g., giant cytoplasmic granules in leucocytes) will not be required.

• Minimum Eligible Age: 1 Month
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Human Genome Research Institute (NHGRI)

NIH

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Wendy J Introne, M.D.

Role: PRINCIPAL_INVESTIGATOR

National Human Genome Research Institute (NHGRI)

Locations

National Institutes of Health Clinical Center

Bethesda, Maryland, United States

Site Status: RECRUITING

Countries

United States

Central Contacts

Wendy J Introne, M.D.

Role: CONTACT

Phone: (301) 451-8879

Email: wi2p@nih.gov

Related Links

https://clinicalstudies.info.nih.gov/cgi/detail.cgi?A_2000-HG-0153.html

NIH Clinical Center Detailed Web Page

Other Identifiers

000153

Identifier Type: -

Identifier Source: org_study_id

00-HG-0153

Identifier Type: -

Identifier Source: secondary_id