Clinical Trial Finder

Inclusion Criteria (Affected Subjects):

• - Male or female of any age; - Suspected or confirmed diagnosis of leukodystrophy or other disorder affecting the white matter of the brain based primarily on the finding of central nervous system neuroimaging consistent with this diagnosis or on an existing diagnosis of a leukodystrophy or genetic leukoencephalopathy as defined in existing classification systems; - Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent; - Willingness to provide clinical data, participate in standardized assessments, and/or provide biologic samples.

Exclusion Criteria (Affected Subjects)

• - Established diagnosis at the time of referral that is not consistent with a genetic disorder of the white matter, such as an acquired demyelinating condition (e.g. multiple sclerosis), or an infectious etiology, with the exception of sequelae of congenital infections such as CMV; - Inability to provide consent.

Inclusion Criteria (Healthy Controls)

• - Male or female of any age; - Individuals with no confirmed or suspected diagnosis of leukodystrophy or other disorder affecting the white matter of the brain; - Documentation of informed consent by the subject, parent, or legal guardian, and, if appropriate, documentation of assent.

Exclusion Criteria (Healthy Controls)

• - Inability to provide consent.

Genetic white matter disorders (leukodystrophies) are estimated to have an incidence of approximately 1:7000 live births. In the past, patients with white matter disease of unknown cause evaluated by the investigator achieved a diagnosis in fewer than 46% of cases after extensive conventional clinical testing. Even when a diagnosis is achieved, the diagnosis takes an average of eight years and this "odyssey" results in testing charges to patients and insurers in excess of $8,000 on average per patient, including patients who never achieve a diagnosis at all. With next generation approaches such as whole exome sequencing, the diagnostic efficacy is closer to 70%, but approximately a third of individuals do not achieve a specific etiologic diagnosis. These diagnostic challenges represent an urgent and unresolved gap in knowledge and disease characterization, as obtaining a definitive diagnosis is of paramount importance for leukodystrophy patients. Moreover, the mechanisms of disease in many leukodystrophies of known cause are very poorly understood, with little known about the best symptomatic management and, thus, limited standards of care are available for the management of these patients. The purpose of this study is to: (Aim 1) Define novel homogeneous groups of patients with unclassified leukodystrophy and work toward finding the cause of these disorders; (Aim 2) assess the validity and utility of next-generation sequencing in the diagnosis of leukodystrophies; (Aim 3) establish disease mechanisms in selected known leukodystrophies; (Aim 4) track current care and natural history of these patients to define the longitudinal course and determinants of outcomes in these disorders; (Aim 5) contact subjects for future research studies and/or clinical programs. This biorepository will use available basic science and clinical research approaches to establish novel diagnoses, biomarkers, and outcome measures for future clinical diagnostic and therapeutic approaches.