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Natural History of the Leukodystrophies

Completed
Conditions
Leukodystrophies
Registration Number
NCT02843555
Lead Sponsor
Baylor Research Institute
Brief Summary

The purpose of this study is to:

1. define novel homogeneous groups of patients with LDs and

2. work toward finding the cause of these disorders.

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
10
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

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Primary Outcome Measures
NameTimeMethod
Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over timeEvery 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
NameTimeMethod
Nerve Biopsy to look for pathological abnormalities in affected nervesBaseline
Neuro-ophthalmological exam to assess for abnormalities in the eyeEvery 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

MRI of the brain to assess involvement of different areas of the brain over timeEvery 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 timeEvery 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

DNA Studies to search for mutations in genes of structural myelin proteins or genes that control myelin productionBaseline
Electromyelogram to assess for changes in muscle function over timeEvery 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 nervesEvery 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

Spinal Tap to look for diagnostic markers of leukodystrophyBaseline
Evoked potentials to assess involvement of different areas of brain over timeEvery 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

Skin biopsy for to look for evidence of storage diseaseBaseline

Trial Locations

Locations (1)

Baylor University Medical Center

🇺🇸

Dallas, Texas, United States

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