Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT00005917 |
| Other study ID # |
000153 |
| Secondary ID |
00-HG-0153 |
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
September 10, 2002 |
Study information
| Verified date |
July 28, 2023 |
| Source |
National Institutes of Health Clinical Center (CC) |
| Contact |
Wendy J Introne, M.D. |
| Phone |
(301) 451-8879 |
| Email |
wi2p[@]nih.gov |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical Trial 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.
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.
