Clinical trial NCT02843555: Natural History of the Leukodystrophies
Official title: The Etiology, Pathogenesis, and Natural History of the Leukodystrophies
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Leukodystrophies
Keywords: Leukodystrophy
Myelin Gene
Myelin Protein
Sural Nerve Biopsy
Undiagnosed Disease
Schwann Cell
White Matter Pathology
Motor Delay
Cognitive Regression
Motor Deterioration
Unknown Disease
Lead sponsor: Baylor Research Institute
Sponsor class: OTHER
First posted: 2016-07-26
Enrollment: 10
Sex: ALL
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: NON_PROBABILITY_SAMPLE
Study population: Subjects identified with a leukodystrophy of unknown etiology

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.

Eligibility criteria: 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

Primary outcomes:
measure: Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over time
timeFrame: Every 52 weeks up to 5 years
Secondary outcomes:
measure: Evoked potentials to assess involvement of different areas of brain over time
timeFrame: Every 52 weeks up to 5 years
measure: MRI of the brain to assess involvement of different areas of the brain over time
timeFrame: Every 52 weeks
measure: Electroencephalogram to assess involvement of different areas of the brain over time
timeFrame: Every 52 weeks up to 5 years
measure: Electromyelogram to assess for changes in muscle function over time
timeFrame: Every 52 weeks up to 5 years
measure: Nerve Conduction study to assess abnormalities in affected nerves
timeFrame: Every 52 weeks up to 5 years
measure: Skin biopsy for to look for evidence of storage disease
timeFrame: Baseline
measure: DNA Studies to search for mutations in genes of structural myelin proteins or genes that control myelin production
timeFrame: Baseline
measure: Spinal Tap to look for diagnostic markers of leukodystrophy
timeFrame: Baseline
measure: Nerve Biopsy to look for pathological abnormalities in affected nerves
timeFrame: Baseline
measure: Neuro-ophthalmological exam to assess for abnormalities in the eye
timeFrame: Every 52 weeks up to 5 years
Other outcomes:
Locations:
city: Dallas
country: United States
facility: Baylor University Medical Center
state: Texas
Study officials:
affiliation: Baylor University Medical Center, Baylor Institute of Metabolic Disease
name: Raphael Schiffmann, MD, MHS
role: PRINCIPAL_INVESTIGATOR
References: