The Myelin Disorders Biorepository Project

Children's Hospital of Philadelphia12,000 enrolled

Overview

The Myelin Disorders Biorepository Project (MDBP) seeks to collect and analyze clinical data and biological samples from leukodystrophy patients worldwide to support ongoing and future research projects. The MDBP is one of the world's largest leukodystrophy biorepositories, having enrolled nearly 2,000 affected individuals since it was launched over a decade ago. Researchers working in the biorepository hope to use these materials to uncover new genetic etiologies for various leukodystrophies, develop biomarkers for use in future clinical trials, and better understand the natural history of these disorders. The knowledge gained from these efforts may help improve the diagnostic tools and treatment options available to patients in the future.

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.

Eligibility

Sex: ALL

Medical Language ↔ Plain English

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, or in the presence of variant(s) of uncertain significance or genotype consistent with leukodytrophy; * 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 (including affected patients' caregivers); * 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.

Locations (23)

Children's Hospital of Los Angeles

Los Angeles, California, United States

RECRUITING

Children's Hospital of Orange County

Orange, California, United States

RECRUITING

Stanford University (Lucile Packard Children's Hospital)

Palo Alto, California, United States

RECRUITING

University of California, Davis (UC Davis Health)

Sacramento, California, United States

Outcomes

Primary Outcomes

Define Novel Homogeneous Groups of Patients with Unclassified Leukodystrophy

In patients with an unclassified leukodystrophy, the study team will collect as much information as available from existing medical records including existing clinical evaluations, neuropsychological/rehabilitation evaluations, and results from blood, urine, spinal fluid, radiological, and peripheral tissue pathological tests. This data will be evaluated to create nosologic groups amongst patients with unclassified leukodystrophy. Additionally, this aim includes the collection and long-term banking of biological samples in subjects with classified and unclassified leukodystrophies to develop a biorepository. These samples will be compared to samples collected from control subjects, either collected directly from enrolled subjects or through existing banked biological samples.