Natural History of the Leukodystrophies

Sponsor

Baylor Research Institute (Other)

Overall Status

Completed

CT.gov ID

NCT02843555

Collaborator

(none)

Enrollment

Location

Study Details

Study Description

Brief Summary

The purpose of this study is to:

define novel homogeneous groups of patients with LDs and
work toward finding the cause of these disorders.

Condition or Disease	Intervention/Treatment	Phase
Leukodystrophies

Detailed Description

Patients with leukodystrophies (LDs) of unknown etiology are a heterogeneous group but constitute the second largest group of genetic white matter diseases. In order to find the cause of leukodystrophies, patients with LDs of unknown cause will be analyzed clinically, neurophysiologically, biochemically and genetically. Patients would have been diagnosed as having no known leukodystrophies at outside centers. At the Baylor University Medical Center, such patients will undergo a series of neuropsychological, blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. Some of these tests will be part of a standard battery while others will be tailored to individual patients. Patients will be followed yearly or as necessary. Patients will be screened for mutations in genes coding for structural myelin proteins. In some patients in whom all tests yielded no information regarding the etiology of their disease, and in whom there is evidence to suggest involvement of the peripheral nervous system, a sural nerve biopsy will be considered. Sural nerve biopsy tissue will be evaluated using a novel combination of approaches including detailed pathological, immunohistochemical, and biochemical analysis of myelin proteins and lipids. Schwann cell biology and expression of myelin genes in the brain will also be investigated in situ. It is hoped that the present study will help clarify the nosology of the leukodystrophies and significantly advance our understanding of the pathogenesis of these diseases.

Study Design

Study Type:

Observational

Actual Enrollment :

10 participants

Observational Model:

Cohort

Time Perspective:

Prospective

Official Title:

The Etiology, Pathogenesis, and Natural History of the Leukodystrophies

Actual Study Start Date :

Jan 23, 2019

Actual Primary Completion Date :

Jan 23, 2019

Actual Study Completion Date :

Jan 23, 2019

Arms and Interventions

Arm	Intervention/Treatment
Leukodystrophy of unknown etiology Subjects who may have an undiagnosed form of leukodystrophy

Outcome Measures

Primary Outcome Measures

Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over time [Every 52 weeks up to 5 years]
Neuropsychological status is evaluated at Baseline and no less than once every year for the duration of the study to assess for any deterioration in function

Secondary Outcome Measures

Evoked potentials to assess involvement of different areas of brain over time [Every 52 weeks up to 5 years]
Evoked potentials are evaluated at Baseline and no less than once every year for the duration of the study to assess for changes in function
MRI of the brain to assess involvement of different areas of the brain over time [Every 52 weeks]
Changes in the brain are assessed at Baseline and no less than once every year for the duration of the study to assess for changes
Electroencephalogram to assess involvement of different areas of the brain over time [Every 52 weeks up to 5 years]
EEG is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function
Electromyelogram to assess for changes in muscle function over time [Every 52 weeks up to 5 years]
EMG is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function
Nerve Conduction study to assess abnormalities in affected nerves [Every 52 weeks up to 5 years]
Nerve conduction is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function
Skin biopsy for to look for evidence of storage disease [Baseline]
DNA Studies to search for mutations in genes of structural myelin proteins or genes that control myelin production [Baseline]
Spinal Tap to look for diagnostic markers of leukodystrophy [Baseline]
Nerve Biopsy to look for pathological abnormalities in affected nerves [Baseline]
Neuro-ophthalmological exam to assess for abnormalities in the eye [Every 52 weeks up to 5 years]
Eyes are assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function

Eligibility Criteria

Criteria

Ages Eligible for Study:

N/A and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

Subjects must:

have clinical and radiographic signs of leukodystrophy without a specific etiology
no diagnosis of adrenoleukodystrophy, adrenomyeloneuropathy, metachromatic leukodystrophy, Krabbe disease, Canavan disease, a well-defined amino acid organic acid disorder, or a systemic mitochondrial cytopathy.
First-degree relatives of patients with leukodystrophies of unknown etiology (father, mother, siblings, or sons and daughters of the patients)
Be able to travel to Baylor University Medical Center in Dallas Texas for evaluation and spend 5-8 working days on site
Be able to tolerate a general exam and neurological exam
Be able to tolerate a modest amount of blood drawing, provide a urine specimen, and have a skin biopsy(if not previously done)
Be able to tolerate the performance of necessary neuroimaging studies to include EEG and Head MRI
Be able to tolerate a neuropsychological testing and rehabilitation evaluation
Be able to tolerate spinal tap or nerve biopsy if needed

Exclusion Criteria:

Unable to travel to Baylor University Medical Center in Dallas Texas for evaluation
Refusal to sign a study consent form
Unable to tolerate the performance of the required testing