Natural History of the Leukodystrophies

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.

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