Natural History of the Leukodystrophies

The Etiology, Pathogenesis, and Natural History of the Leukodystrophies

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.

Study Overview

• Status: Completed
• Conditions: 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 Type: Observational
• Enrollment (Actual): 10

Contacts and Locations

Study Locations

• United States
  • Texas
    • Dallas, Texas, United States, 75246
      • Baylor University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Subjects identified with a leukodystrophy of unknown etiology

Description

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 Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Leukodystrophy of unknown etiology; Subjects who may have an undiagnosed form of leukodystrophy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Neuropsychological evaluation to measure baseline cognitive function and detect signs of dementia over time	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	Every 52 weeks up to 5 years

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Evoked potentials to assess involvement of different areas of brain over time	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	Every 52 weeks up to 5 years
MRI of the brain to assess involvement of different areas of the brain over time	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	Every 52 weeks
Electroencephalogram to assess involvement of different areas of the brain over time	EEG is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function	Every 52 weeks up to 5 years
Electromyelogram to assess for changes in muscle function over time	EMG is assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function	Every 52 weeks up to 5 years
Nerve Conduction study to assess abnormalities in affected nerves	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	Every 52 weeks up to 5 years
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	Eyes are assessed at Baseline and no less than once a year for the duration of the study to assess for changes in function	Every 52 weeks up to 5 years

Collaborators and Investigators

• Sponsor: Baylor Research Institute
• Investigators: Principal Investigator: Raphael Schiffmann, MD, MHS, Baylor University Medical Center, Baylor Institute of Metabolic Disease

Study record dates

Study Major Dates

• Study Start (ACTUAL): January 23, 2019
• Primary Completion (ACTUAL): January 23, 2019
• Study Completion (ACTUAL): January 23, 2019

Study Registration Dates

• First Submitted: April 7, 2016
• First Submitted That Met QC Criteria: July 21, 2016
• First Posted (ESTIMATE): July 26, 2016

Study Record Updates

• Last Update Posted (ACTUAL): March 22, 2019
• Last Update Submitted That Met QC Criteria: March 21, 2019
• Last Verified: March 1, 2019

More Information

Terms related to this study

• Keywords: Leukodystrophy; Sural Nerve Biopsy; Myelin Gene; Myelin Protein; Undiagnosed Disease; Schwann Cell; White Matter Pathology; Motor Delay; Cognitive Regression; Motor Deterioration; Unknown Disease
• Other Study ID Numbers: 008-169

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO